Absolute Stability for Fracture Repair

Absence of fracture micromotion under physiological load following fixation. This results in primary bone healing. Best achieved with anatomic reduction and interfragmentary compression.

Rüedi, Thomas P., et al. AO principles of fracture management. Stuttgart: Thieme, 2000.

Kojima, Kodi Edson, and Robinson Esteves Santos Pires. "Absolute and relative stabilities for fracture fixation: the concept revisited." Injury 48 (2017): S1.

Contributor: Augustine Saiz

ACI

Autologous chondrocyte implantation is a cell-based treatment for focal cartilage lesions that consists in two steps: 1) arthroscopic evaluation of the chondral defect and articular cartilage biopsy and; 2) implantation of cultured chondrocytes.

1. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331(14): 889–95.
2. Minas T, Von Keudell A, Bryant T, et al. The John Insall award: a minimum 10-year outcome study of autologous chondrocyte implantation. Clin Orthop Relat Res 2014;472(1):41–51.

Contributor: Youping Tao

Acromiohumeral Distance

The Acromiohumeral Distance is measured as the shortest distance between the dense cortical bone at the inferior aspect of the acromion to the subchondral lamina of the humeral head. It can be measured on conventional radiographs. It is about 10mm in males and about 9mm in females. (1) Patients with a reduced Acromial humeral distance have a high prevalence of full-thickness rotator cuff tears. (2)

1. Petersson CJ, Redlund-Johnell I. The subacromial space in normal shoulder radiographs. Acta Orthopaedica Scandinavica. Januar 1984;55(1):57–8. 

2. Saupe N, Pfirrmann CWA, Schmid MR, Jost B, Werner CML, Zanetti M. Association Between Rotator Cuff Abnormalities and Reduced Acromiohumeral Distance. American Journal of Roentgenology. August 2006;187(2):376–82. 

Contributor: Laura Hauer

Advanced therapy medicinal product (ATMP)

Advanced therapy medicinal product means any of the following medicinal products for human use: a gene therapy medicinal product, a somatic cell therapy medicinal product, or a tissue engineered product. Gene therapy medicines: contain genes that lead to a therapeutic, prophylactic or diagnostic effect. They work by inserting 'recombinant' genes into the body, usually to treat a variety of diseases, including genetic disorders, cancer or long-term diseases. Somatic-cell therapy medicines: contain cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential functions in the body. They can be used to cure, diagnose or prevent diseases. Tissue-engineered medicines: contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue.

1. The European Parliament and The Council of the European Union. Regulation (EC) No 1394/2007 Of The European Parliament and of The Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Union [Internet]. 2007 [cited 2021 May 23];L324/121:1–17. Available from: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:324:0121:0137:en:PDF

Contributor: Kieran Joyce

Age-related changes in the spine

Each of the structures/tissues comprising the spine—bony vertebrae and spinal processes, fibrous/cartilaginous intervertebral discs, and spinal ligaments, like those of other musculoskeletal organs, undergo age-related changes in their composition and properties. In recent years, age-related degeneration of cervical and lumbar intervertebral discs, as a cause of neck and back pain, has been receiving increasing attention in spinal research. Recently, several studies have reported that the age-related change of the spinal sagittal alignment and balance, such as cervical spine parameters (cervical lordosis, C2 slope, C7 slope), thoracic kyphosis, lumbar lordosis and sacropelvic parameters (pelvic tilt, sacral slope and pelvic incidence) et al. Many of the studies elucidated the relationship between radiographic parameters and the health-related quality-of-life (HRQOL), and heighted the importance of the sagittal parameters. In brief, the field of the aging of the spine offers many basic and clinical research opportunities. For example, in the basic research, the molecular mechanisms of the osteoporosis or intervertebral disc degeneration should be investigated deeply. For providing the clinical reference, multicenter-study and big data collection are also needed and epidemiological studies to investigate age-related differences in spinal degenerative phenotypes (e.g., Schmorl nodes, Modic changes) and age-related difference in sagittal parameters and their association with clinical symptoms (e.g., low back pain). Better understanding the aging of spine, better treatment for the spinal conditions.

Contributor: Youping Tao

Aggrecan

Aggrecan is a high molecular weight proteoglycan constituted by a protein core provided with several chains of chondroitin sulfate and keratan sulfate. Together with type II collagen, aggrecan is one of the main components of the extracellular matrices of articular cartilage and intervertebral disc. Due to the high content of negatively charged glycosaminoglycan and their water-binding properties, it provides these tissues with swelling pressure and the capacity to resist compressive loads.

- Sivan SS, Wachtel E, Roughley P. Structure, function, aging and turnover of aggrecan in the intervertebral disc. Biochim Biophys Acta. 2014;1840(10):3181-3189. doi:10.1016/j.bbagen.2014.07.013

- Aspberg A. The different roles of aggrecan interaction domains. J Histochem Cytochem. 2012;60(12):987-996. doi:10.1369/0022155412464376

Contributor: Luca Ambrosio

AI in orthopaedics

Artificial Intelligence (AI) in orthopaedics refers to the application of machine learning algorithms and cognitive computing to enhance orthopaedic care. AI systems analyze medical data to assist in designing custom orthotics, improve diagnostic accuracy, and optimize surgical outcomes. For instance, AI algorithms process imaging data to detect anomalies in bone structure and predict the success of joint replacement surgeries. AI also contributes to postoperative care, monitoring patient recovery through wearable devices that provide real-time data to healthcare professionals.

Contributor: Rocco Maria Panzera

Alarmin

Alarmins, a type of damage-associated molecular patterns (DAMP), are endogenous molecules that are constitutively expressed and have normal physiological functions. However, when cells are stressed or damaged these molecules are released and become pro-inflammatory and chemotactic - stimulating and recruiting immune cells and increasing inflammation locally. S100A8/A9 and high-mobility group box 1 (HMGB1) are common alarmins found in arthritic or post-traumatic joints. Alarmins are frequently ligands of Toll-like receptors, and other Pattern Recognition Receptors such as RAGE which stimulate the innate immune system and pathways.

• Joost J Oppenheim, De Yang. Alarmins: chemotactic activators of immune responses, Current Opinion in Immunology, Volume 17, Issue 4, 2005, pg 359-365, ISSN 0952-7915, https://doi.org/10.1016/j.coi.2005.06.002.

Contributor: Dustin Leale

Allograft

A bone or a tissue that is transplanted from one person to another. They are sterilized and medically processed tissues, that come from a donor, or they are cadaveric. Advantages are the short procedure, no second surgical site and that it is a safe alternative to patient’s tissue. Disadvantages are the risk of rejection by the body and longer healing process.

Contributor: Georgios Chalatsis

All-suture Anchor

The all-suture anchor is the fifth and most recent generation of anchor stitches for reattaching soft tissue during arthroscopic procedures on the shoulder and knee. Its advantage over previous generations of anchors lies in its smaller diameter, which causes less damage at the application site and is easier to insert. Biomechanical studies confirm that the all-suture anchor exhibits comparable values in terms of pull-out forces and stiffness.

• Berthold DP, Mazzocca AD. Editorial Commentary: A New Star Is Born-The Knotless All-Suture Anchor. Arthroscopy. 2020 Jun;36(6):1533-1534. doi: 10.1016/j.arthro.2020.03.020. PMID: 32503769.
• Lacheta L, Brady A, Rosenberg SI, Dornan GJ, Dekker TJ, Anderson N, Altintas B, Krob JJ, Millett PJ. Biomechanical Evaluation of Knotless and Knotted All-Suture Anchor Repair Constructs in 4 Bankart Repair Configurations. Arthroscopy. 2020 Jun;36(6):1523-1532. doi: 10.1016/j.arthro.2020.01.046. Epub 2020 Feb 10. PMID: 32057982.
• Picture Copyrights: Arthrex, Naples, FL
  
  

Contributor: Lorenz Pichler

Alpha Granules

Platelets’ organelles involved in the storage and release of platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β), among over 300 proteins. They are the most numerous granules in the platelet, playing a key role in hemostasis of vessel repair, blood coagulation, and platelet aggregation. Hemostasis can be considered the first stage of tissue healing.

Contributor: Theodorakys Marín Fermín

AMADEUS Score

This magnetic resonance (MR)-based classification system was developed in order to evaluate and grade osteochondral lesions prior to cartilage surgery. The AMADEUS score is a three-part classification system rating cartilage defect size, depth, and subchondral bone of the defect providing a three-digit code for each part based on the various defect characteristics

Jungmann PM, Welsch GH, Brittberg M, Trattnig S, Braun S, Imhoff AB, Salzmann GM. Magnetic Resonance Imaging Score and Classification System (AMADEUS) for Assessment of Preoperative Cartilage Defect Severity. Cartilage. 2017 Jul;8(3):272-282. doi: 10.1177/1947603516665444. Epub 2016 Aug 25. PMID: 28618873; PMCID: PMC5625863.

Contributor: Juan Manuel Ramirez

Amniotic Suspension Allograft (ASA)

Placental-derived tissue comprised of amniotic membrane particulate and amniotic fluid cells and containing a host of growth factors, inflammatory modulators, and cytokines, as well as a high content of hyaluronic acid, hypothesized to reduce the burden of symptomatic osteoarthritis through anti-inflammatory and chondroregenerative properties.

1. Vines JB, Aliprantis AO, Gomoll AH, Farr J. Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. J Knee Surg. 2016 Aug;29(6):443-50. doi: 10.1055/s-0035-1569481. Epub 2015 Dec 18. PMID: 26683979.

Contributor: Bryson Kemler

Angiogenesis

Formation of blood vessels, from an existing vascular network, stimulated by growth factors. Crucial to human growth and development. Important in wound healing, bone, and muscle regeneration.

Zhang Y, Xie Y, Hao Z, Zhou P, Wang P, Fang S, Li L, Xu S, Xia Y. Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis. ACS Appl Mater Interfaces. 2021 Apr 28;13(16):18472-18487. doi: 10.1021/acsami.0c22671. Epub 2021 Apr 15. Erratum in: ACS Appl Mater Interfaces. 2022 Mar 30;14(12):14834-14835. PMID: 33856781.

Qi X, Zhang J, Yuan H, Xu Z, Li Q, Niu X, Hu B, Wang Y, Li X. Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats. Int J Biol Sci. 2016 May 25;12(7):836-49. doi: 10.7150/ijbs.14809. PMID: 27313497; PMCID: PMC4910602.

Song Y, Wu H, Gao Y, Li J, Lin K, Liu B, Lei X, Cheng P, Zhang S, Wang Y, Sun J, Bi L, Pei G. Zinc Silicate/Nano-Hydroxyapatite/Collagen Scaffolds Promote Angiogenesis and Bone Regeneration via the p38 MAPK Pathway in Activated Monocytes. ACS Appl Mater Interfaces. 2020 Apr 8;12(14):16058-16075. doi: 10.1021/acsami.0c00470. Epub 2020 Mar 26. PMID: 32182418.

Contributor: Bryce Clinger

Ankle Sprain

An injury that occurs when you roll, twist or turn your ankle in a supraphysiological way. This can stretch or tear ankle ligaments. A sprained ankle occurs when the ligaments are forced beyond their normal range of motion. Most sprained ankles involve injuries to the ligaments on the lateral side of the ankle. Ankle injuries are currently the fourth most common injury in elite football. Treatment for a sprained ankle depends on the severity of the injury. Lower grade injuries can be managed conservatively, whereas higher grade injuries may require surgical management.

(1)    D'Hooghe P, Cruz F, Alkhelaifi K. Return to Play After a Lateral Ligament Ankle Sprain. Curr Rev Musculoskelet Med. 2020 Jun;13(3):281-288. doi: 10.1007/s12178-020-09631-1. PMID: 32377961; PMCID: PMC7251008.

(2)    Kerkhoffs GM, van den Bekerom M, Elders LA, van Beek PA, Hullegie WA, Bloemers GM, de Heus EM, Loogman MC, Rosenbrand KC, Kuipers T, Hoogstraten JW, Dekker R, Ten Duis HJ, van Dijk CN, van Tulder MW, van der Wees PJ, de Bie RA. Diagnosis, treatment and prevention of ankle sprains: an evidence-based clinical guideline. Br J Sports Med. 2012 Sep;46(12):854-60. doi: 10.1136/bjsports-2011-090490. Epub 2012 Apr 20. PMID: 22522586.

Contributor: Matthias Peiffer

Anterior cruciate ligament

The anterior cruciate ligament is an intra-articular ligament of the knee coursing from the distal femur to the proximal tibia. It is comprised of two bundles, anteromedial (AMB) and posteromedial (PLB). These bundles show different properties in knee range of motion, as AMB lengthens and PLB shortens during flexion (1,2). The ligament is made mostly of type I collagen and resists translatory and rotatory forces providing important knee stability (1,3). It is commonly subject to injury and its injury is one of the most diagnosed intra-articular injuries of the knee (4). The ACL being in an intra-articular environment causes it not to be able to heal on its own (2), which requires either early repair or early or late reconstruction surgery necessary if conservative therapy fails (4,5). Several follow-up studies on patients with an ACL tear showed that even after reconstruction surgery, these patients show signs of degenerative changes in the knee joint (6,7). A registry study showed that patients who had an ACL reconstruction had an increased risk of knee arthroplasty at 15 years (8). Another study showed that patients with bilaterally reconstructed ACLs had inferior functional outcomes than those who had unilateral injury and reconstruction, further supporting the theory, that ACL injury is associated with the worse outcome even after a reconstruction (9). However, there are studies reporting better functional outcomes in ACL injured patients after operative treatment (10,11). To better clinical outcomes, current studies evaluate individualized treatment options and the importance of addressing concomitant injuries or bony anatomy (12,13). The anterior cruciate ligament is an intra-articular ligament of the knee coursing from the distal femur to the proximal tibia. It is comprised of two bundles, anteromedial (AMB) and posteromedial (PLB). These bundles show different properties in knee range of motion, as AMB lengthens and PLB shortens during flexion (1,2). The ligament is made mainly of type I collagen and resists translatory and rotatory forces providing important knee stability (1,3). It is commonly subject to injury and its injury is one of the most diagnosed intra-articular injuries of the knee (4). The ACL being in an intra-articular environment causes it not to be able to heal on its own (2), which requires either early repair or early or late reconstruction surgery necessary if conservative therapy fails (4,5).

1. Duthon VB, Barea C, Abrassart S, Fasel JH, Fritschy D, Ménétrey J. Anatomy of the anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc. 2006;14(3):204-213. doi:10.1007/s00167-005-0679-9
2. Musahl V, Nazzal EM, Lucidi GA, et al. Current trends in the anterior cruciate ligament part 1: biology and biomechanics. Knee Surg Sports Traumatol Arthrosc. 2022;30(1):20-33. doi:10.1007/s00167-021-06826-y
3. Li G, Papannagari R, DeFrate LE, Yoo JD, Park SE, Gill TJ. The effects of ACL deficiency on mediolateral translation and varus-valgus rotation. Acta Orthop. 2007;78(3):355-360. doi:10.1080/17453670710013924
4. Musahl V, Karlsson J. Anterior Cruciate Ligament Tear. N Engl J Med. 2019;380(24):2341-2348. doi:10.1056/NEJMcp1805931
5. Hoogeslag RAG, Huis In 't Veld R, Brouwer RW, de Graaff F, Verdonschot N. Acute Anterior Cruciate Ligament Rupture: Repair or Reconstruction? Five-Year Results of a Randomized Controlled Clinical Trial. Am J Sports Med. 2022;50(7):1779-1787. doi:10.1177/03635465221090527

Contributor: M. Enes Kayaalp

Arthroscopy

The term arthroscopy refers to a minimally invasive surgical procedure that involves visual examination of the interior of the joint. An Arthroscope - a special small camera - is used to diagnose and treat various conditions or injuries of a joint.

Contributor: Lena Eggeling

Atrophy

A diminution in the size of a cell, tissue, organ, or part.

Contributor: Myron Spector

Autocrine

Denoting the influence of chemical factors secreted by a cell on itself.

Contributor: Myron Spector

Autograft

A bone or a tissue that is transferred from one spot to another on the patient’s body. Its advantages are fast healing and minimal risk of infection. On the other hand, the disadvantages are that relies on patient’s tissue quality, multiple surgical sites and longer procedure.

Contributor: Georgios Chalatsis

Avascular Bone Necrosis

The cellular death of bone components as a result of deprivation of blood circulation.

Contributor: Mariya Hadzhinikolova

Benninghoff Arcades

The Benninghoff arcade model assumpts an arcade pattern organization of the collagen network in articular cartilage. It is named after Alfred Benninghoff who originally described this millimeter scaled hierarchical collagen structure in 1925. The directionality of the collagen fibril network is divided: in the surface zone it is starting with a tangential (parallel) alignment, then it is progressively arcading (transitional zone) into radial mid-to-deep zones followed by the linkage at the bone interface.

1) Klika, V; Gaffney, EA; Chen, Y-C; Brown, CP (2016): An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology. In: Journal of the mechanical behavior of biomedical materials 62, S. 139–157. DOI: 10.1016/j.jmbbm.2016.04.032.

2) Brown, ETT; Damen, AHA; Thambyah, A (2020): The mechanical significance of the zonally differentiated collagen network of articular cartilage in relation to tissue swelling. In: Clinical biomechanics (Elsevier), DOI: 10.1016/j.clinbiomech.2019.12.008.

Contributor: Theresia Stich

Biocompatibility

Biocompatibility is the ability of an implant material to function in-vivo without eliciting detrimental local or systemic responses in the body (1). It is a key concept in understanding the host response to implants and biomaterials (host-material interaction), which is essential to developing medical implants and improving the performance of those implants (2).

         1- M.R. Cohn et al. in Comprehensive Biomaterials II, 2017

2       2-Buddy D. Ratner, in Host Response to Biomaterials, 2015

Contributor: Sara Ahmed Hassouna Elsayed

bioink

Term for the bioprintable materials used in three-dimensional bioprinting processes. Bioink, composed of cells and other biologics, is used to fabricate living tissues and organs such as bone and cartilage.

Gungor-Ozkerim PS , Inci I , Zhang YS , Khademhosseini A , Dokmeci MR . Bioinks for 3D bioprinting: an overview. Biomater Sci. 2018 May 1;6(5):915-946. doi: 10.1039/c7bm00765e. PMID: 29492503; PMCID: PMC6439477.

Dey M, Ozbolat IT. 3D bioprinting of cells, tissues and organs. Sci Rep. 2020 Aug 18;10(1):14023. doi: 10.1038/s41598-020-70086-y. PMID: 32811864; PMCID: PMC7434768.

Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT. The bioink: A comprehensive review on bioprintable materials. Biotechnol Adv. 2017 Mar-Apr;35(2):217-239. doi: 10.1016/j.biotechadv.2016.12.006. Epub 2017 Jan 3. PMID: 28057483.

Contributor: Anna Redden

Biologic

Products of living organisms, and the organisms themselves.

Contributor: Myron Spector

Biological Augmentation

A substance or material added to enhance the underlying tissue or repair in a procedure, examples include injectables such as PRP, patch augmentation of rotator cuff repair, or bone graft for defects.

Contributor: Richard Danilkowicz

Biological Engineering

The application of principles of biology and the tools of engineering to create usable, tangible, economically viable products. When applied towards medicine the term biomedical engineering can be adopted. 

Contributor: Zaamin Hussain

Biomaterial

A material used for the fabrication of an implantable medical device.

Contributor: Myron Spector

Biomechanics

Biomechanics is defined as the study of function, motion and structure of the mechanical aspects of biological systems. Despite inherent limitations, the role of biomechanical studies should not be under-estimated in orthopaedic medicine, as they can be enlightening.3 Biomechanical studies represent a first step in evaluation of surgical techniques which are subsequently translated to a clinically relevant purpose.1, 2, 3

Contributor: Daniel Berthold

Biomimetics

Biomimetics generally refers to the synthesis of materials/devices that reflect/mimic biological structures and/or processes. Significant research in the field of Orthopaedics have been made to produce biomimetic products which will branch the unattainable regenerative potential of the human body such as scaffolds for nonunion bone fracture healing.

Contributor: Josephine Luk

Bioprinting

Bioprinting is an advanced manufacturing process that utilizes 3D printing technologies to fabricate complex, three-dimensional tissues and organs by precisely placing cells, growth factors, and biomaterials. The technology operates by layer-by-layer deposition of bioinks—mixtures containing biocompatible materials, cells, and supporting components—allowing for the creation of structures with cellular and extracellular matrix-like complexity.

[1]Murphy, S. V., De Coppi, P., & Atala, A. (2020). Opportunities and challenges of translational 3D bioprinting. Nature biomedical engineering, 4(4), 370–380. 
[2]Liu, Y., Peng, L., Li, L., Huang, C., Shi, K., Meng, X., Wang, P., Wu, M., Li, L., Cao, H., Wu, K., Zeng, Q., Pan, H., Lu, W. W., Qin, L., Ruan, C., & Wang, X. (2021). 3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model. Biomaterials, 279, 121216. 

Contributor: Lang Bai

Biosensor

A biosensor is a compact analytical device that combines a biological component, such as enzymes, antibodies, or DNA, with a transducer to detect and quantify specific biological or chemical molecules. These devices are designed to convert the biological response, such as binding with a target molecule, into a measurable signal, typically electrical, optical, or chemical. Biosensors have a wide range of applications, including in healthcare for diagnostic purposes, environmental monitoring, and food safety testing. They play a crucial role in providing real-time and accurate information about various biological processes and substances.

Zuncheddu D, Della Bella E, Schwab A, Petta D, Rocchitta G, Generelli S, Kurth F, Parrilli A, Verrier S, Rau JV, Fosca M, Maioli M, Serra PA, Alini M, Redl H, Grad S, Basoli V. Quality control methods in musculoskeletal tissue engineering: from imaging to biosensors. Bone Res. 2021 Oct 27;9(1):46. doi: 10.1038/s41413-021-00167-9. Erratum in: Bone Res. 2021 Dec 28;9(1):51. PMID: 34707086; PMCID: PMC8551153.

Contributor: Valentina Basoli

Biotribology

The study of surfaces undergoing contact and relative motion in biological settings. Articular cartilage, and its repair and replacement are of particular interest to this field of study. Active areas of research include methods to measure [1,2], control [3,4], and elucidate [5–7] the underlying mechanisms that cause friction, wear, and lubrication.

Contributor: Axel Moore

Birefringence

An optical property describing the double refraction of light at different rates across a sample’s extraordinary and ordinary axes. In biological tissues, birefringence is caused by the structural anisotropy of the underlying collagen fiber network. Many collagenous tissues exhibit birefringence, such as eye cornea, tendon, cartilage, eye sclera, dura mater, muscle, nerve, retina, bone, teeth, and myelin. The more highly aligned the collagen fiber network is, the greater the birefringence. A tissue’s birefringence, and subsequently its underlying collagen fiber alignment, can be measured using polarized light imaging techniques, such as quantitative polarized light imaging or QPLI.

York, Timothy, Lindsey Kahan, Spencer P. Lake, and Viktor Gruev. "Real-time high-resolution measurement of collagen alignment in dynamically loaded soft tissue." Journal of biomedical optics 19, no. 6 (2014): 066011.

Wang, L. V., and D. A. Zimnyakov. Optical polarization in biomedical applications. New York (NY): Springer, 2006.

Ghosh, Nirmalya, and Alex I. Vitkin. "Tissue polarimetry: concepts, challenges, applications, and outlook." Journal of biomedical optics 16, no. 11 (2011): 110801.

Tuchin, Valery V. "Polarized light interaction with tissues." Journal of biomedical optics 21, no. 7 (2016): 071114.

Contributor: Leanne Iannucci

BMAC

Bone marrow aspirate concentrate is a preparation of harvested autologous bone marrow subjected to centrifugation with the goal of concentrating growth factors, white blood cells, platelets, and mesenchymal stem cells.

Contributor: LEONARDO CAVINATTO

BMP-7

Bone morphogenetic protein 7 is a protein that in humans is encoded by the BMP7 gene. While it plays a key role in the transformation of mesenchymal cells into bone and cartilage, it also contributes in important ways to processes in non-musculoskeletal tissues: e.g., it plays a role in kidney development through induction of MET of the metanephrogenic blastema.

Zeisberg M, Bottiglio C, Kumar N, Maeshima Y, Strutz F, Müller GA, Kalluri R (December 2003). "Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models". American Journal of Physiology. Renal Physiology. 285 (6): F1060–7. doi:10.1152/ajprenal.00191.2002.

Contributor: jingjing Gao

Bone marrow stimulation

Bone marrow stimulation (BMS) is a surgical technique that is used to repair cartilage damage, such as in (osteo)chondral lesions. The aim of the procedure is to create microfractures which allows stem cells from the subchondral bone to reach the defect and stimulate the growth of cartilage. BMS is often used in knee (osteo)chondral defects and the most used treatment for primary osteochondral lesions of the talus.

1. Rikken QGH, Dahmen J, Stufkens SAS, Kerkhoffs GMMJ. Satisfactory long-term clinical outcomes after bone marrow stimulation of osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc. 2021 Nov;29(11):3525-3533. doi: 10.1007/s00167-021-06630-8. Epub 2021 Jun 29. PMID: 34185110; PMCID: PMC8514351.

2. Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc. 2014 Sep;22(9):1986-96. doi: 10.1007/s00167-013-2676-8. Epub 2013 Sep 20. PMID: 24051505.

3. Dahmen J, Lambers KTA, Reilingh ML, van Bergen CJA, Stufkens SAS, Kerkhoffs GMMJ. No superior treatment for primary osteochondral defects of the talus. Knee Surg Sports Traumatol Arthrosc. 2018 Jul;26(7):2142-2157. doi: 10.1007/s00167-017-4616-5. Epub 2017 Jun 27. PMID: 28656457; PMCID: PMC6061466.

Contributor: Julian Hollander

BRMS

Biologically regulated marrow stimulation is when a microfracture procedure is performed in conjunction with administration of an angiotensin receptor blocker. Method to improve microfracture aiming for a potentially more anatomic articular cartilage rather than fibrocartilage.

Contributor: Teresa Hall

Carrageenan-based biomaterial

Carrageenan-based injectable scaffold along with gelatin demonstrated a statistically significant gelation property when doped with stem cells in vitro. The cellular adhesion, viability, and cytotoxicity assay demonstrated no senescence or toxicity to the cells. The trilineage property of stem cells was maintained. Injectable scaffolds along with the stem cells exhibited chondrogenic gene expression. The proper combination of polymers, cells, and bioactive molecules used in the fabrication of injectable hydrogels, physical and chemical cross-linking, ensures the excellent design of injectable hydrogels for cartilage repair to improve the quality and longevity of repair tissue and ultimately patient outcome.

1. Amorim D, Fonseca-Rodrigues D, David-Pereira A, Costa O, Lima AP, Nogueira R, Cruz R, Martins AS, Sousa L, Oliveira F, Pereira H, Pirraco R, Pertovaara A, Almeida A, Pinto-Ribeiro F. Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis. Pain. 2023 Nov 1;164(11):2477-2490. doi: 10.1097/j.pain.0000000000002954. Epub 2023 Jun 28. PMID: 37390363.

2. Pacheco-Quito EM, Ruiz-Caro R, Veiga MD. Carrageenan: Drug Delivery Systems and Other Biomedical Applications. Mar Drugs. 2020 Nov 23;18(11):583. doi: 10.3390/md18110583. PMID: 33238488; PMCID: PMC7700686.

Contributor: Madhan Jeyaraman

Cartilage

Cartilage is an avascular and aneural connective tissue with limited regenerative capacity composed of 95% extracellular matrix (collagen fibers, glycosaminoglycans, proteoglycans, and elastin fibers) and 5% chondrocytes that forms our skeleton and is able to tolerate an immense amount of repetitive physical stress. The three types of cartilage are hyaline cartilage, elastic cartilage and fibrocartilage; each differing in the amounts of proteoglycans and collagen.

Contributor: Michael Mijares

Cartilage Debridement

The most common surgical procedure to remove damaged unstable articular cartilage and gold standard treatment for partial thickness cartilage lesions. It can be performed arthroscopically with mechanical (shaver or curette) or thermal instrumentation (radiofrequency devices).

Contributor: Theodorakys Marín Fermín

Caspase

Caspases are a family of cysteine-dependent aspartate-specific proteases that play crucial roles in apoptosis (programmed cell death) and inflammation. These enzymes are synthesized as inactive zymogens (procaspases) and become activated through proteolytic cleavage or scaffold-mediated transactivation.[1-3] Caspases are broadly classified into two main categories based on their functions: apoptotic caspases and inflammatory caspases. Apoptotic caspases are further subdivided into initiator caspases (e.g., caspase-8, caspase-9) and executioner caspases (e.g., caspase-3, caspase-6, caspase-7). Initiator caspases respond to apoptotic signals and activate executioner caspases, which then cleave various cellular substrates to orchestrate cell death.[4-6] Inflammatory caspases, such as caspase-1, caspase-4, and caspase-5 in humans, are involved in the maturation of pro-inflammatory cytokines and the promotion of inflammatory responses. Caspase-1, for example, processes pro-interleukin-1β into its active form, a key step in the inflammatory response.[2][5][7] The dysregulation of caspase activity is implicated in various diseases, including cancer, autoimmune disorders, and neurodegenerative diseases. Understanding the mechanisms of caspase activation and regulation is essential for developing therapeutic strategies targeting these enzymes.[2][6][8] In summary, caspases are essential proteases involved in the regulation of apoptosis and inflammation, with significant implications for human health and disease.

1. Cohen GM. Caspases: the executioners of apoptosis. Biochem J. 1997;326 ( Pt 1)(Pt 1):1-16. doi:10.1042/bj3260001
2. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease [published correction appears in Cold Spring Harb Perspect Biol. 2015 Apr 01;7(4):a026716. doi: 10.1101/cshperspect.a026716]. Cold Spring Harb Perspect Biol. 2013;5(4):a008656. Published 2013 Apr 1. doi:10.1101/cshperspect.a008656
3. Stennicke HR, Salvesen GS. Catalytic properties of the caspases. Cell Death Differ. 1999;6(11):1054-1059. doi:10.1038/sj.cdd.4400599
4. Kumar S, Dorstyn L, Lim Y. The role of caspases as executioners of apoptosis. Biochem Soc Trans. 2022;50(1):33-45. doi:10.1042/BST20210751
5. Chowdhury I, Tharakan B, Bhat GK. Caspases - an update. Comp Biochem Physiol B Biochem Mol Biol. 2008;151(1):10-27. doi:10.1016/j.cbpb.2008.05.010
6. Chang HY, Yang X. Proteases for cell suicide: functions and regulation of caspases. Microbiol Mol Biol Rev. 2000;64(4):821-846. doi:10.1128/MMBR.64.4.821-846.2000
7. Kesavardhana S, Malireddi RKS, Kanneganti TD. Caspases in Cell Death, Inflammation, and Pyroptosis. Annu Rev Immunol. 2020;38:567-595. doi:10.1146/annurev-immunol-073119-095439
8. Sahoo G, Samal D, Khandayataray P, Murthy MK. A Review on Caspases: Key Regulators of Biological Activities and Apoptosis. Mol Neurobiol. 2023;60(10):5805-5837. doi:10.1007/s12035-023-03433-5
   

Contributor: Jian Mei

Caton-Deschamps Index

The Caton-Deschamps index is a radiological measurement used to determine patellar height in the knee, assessed on standing lateral knee radiographs. It is calculated by measuring the distance between the lower border of the patellar articular surface and the anterosuperior edge of the tibia, divided by the length of the patellar articular surface itself. This index is particularly useful in identifying patella alta, a condition where the patella is positioned abnormally high. A Caton-Deschamps index greater than 1.2 typically indicates patella alta, while an index less than 0.8 suggests patella baja (a low-lying patella).

Caton J, Deschamps G, Chambat P, Lerat JL, Dejour H (1982) Patella infera. Apropos of 128 cases. Rev Chir Orthop Reparatrice Appar Mot 68:317–325

Contributor: Adrian Deichsel

Cell microenvironment

Domain (~ 100 µm diameter) that surrounds the volume occupied by a specific cell in its native niche. Therefore, the cell microenvironment comprises the interactions of each cell with the neighbouring ones, the soluble factors, the organized three-dimensional structure that supports the cells and distributes the bioactive factors named as extracellular matrix (ECM), and the physical fields that determine the mechanic and electrophysiology of the natural tissue (1). Due to the complexity, heterogeneity and dynamicity of the cell microenvironment, this cellular space has a considerable impact on regulating the cell behaviour, development and physiology (2). For that reason, the cell microenvironment is a key term in regenerative medicine, since it appears necessary to mimic the native biochemical and biophysical cues of the functional tissue in order to support its functionality in the long term (3).

1. Huang GY, Li F, Zhao X, Ma YF, Li YH, Lin M, et al. Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment. Chemical Reviews. 2017;117(20):12764-850.
2. Vinatier C, Mrugala D, Jorgensen C, Guicheux J, Noel D. Cartilage engineering: a crucial combination of cells, biomaterials and biofactors. Trends in Biotechnology. 2009;27(5):307-14.
3. Camarero-Espinosa S, Rothen-Rutishauser B, Foster EJ, Weder C. Articular cartilage: from formation to tissue engineering. Biomaterials Science. 2016;4(5):734-67.

Contributor: Sandra Ramos-Díez

chemically modified messenger RNA (cmRNA)

Chemically modified mRNA refers to a form of messenger RNA (mRNA) that has been altered or enhanced through the introduction of chemical modifications to improve its stability, translatability, reduce immunogenicity and other properties.

[1] U. Sahin, K. Kariko, O. Tureci, mRNA-based therapeutics--developing a new class of drugs, Nature Reviews Drug Discovery, 13 (2014) 759-780.

[2] W.V. Gilbert, T.A. Bell, C. Schaening, Messenger RNA modifications: form, distribution, and function, Science, 352 (2016) 1408-1412.

Contributor: Claudia Del Toro Runzer

Chemokines

Chemokines are secreted by cells to modulate the local or systemic immune response from white blood cells. They are implicated in both tissue regeneration and degeneration. These substances are generally cytokines that serve this specific role within a tissue environment. Modulation of these factors or additions chemokines through concentration from preparations like Bone Marrow Aspirate Concentrate (BMAC) or platelet-rich plasma (PRP) can stimulate healing or regeneration in disease tissues.

Contributor: Austin Stone

Chondrocyte

Chondrocyte is the only resident cell type in articular cartilage. Chondrocytes are highly specialized, metabolically active cells that play a unique role in the development, maintenance, and repair of the ECM. They originate from mesenchymal stem cells and constitute about 2% of the total volume of articular cartilage. Each chondrocyte establishes a specialized microenvironment and is responsible for the turnover of the ECM in its immediate vicinity.

Contributor: Jin Cheng

Chondron

A chondron is defined as a chondrocytes plus it’s surrounding pericellular matrix. Obtained through rapid digestion of cartilage, these cells have been investigated in clinical trials for their use in treating articular cartilage defects of the knee.

Contributor: Katherine Lydon

Collagen

Collagen is categorized into 28 subtypes and constitutes the most abundant protein in the body by weight.1 Collagens are the main structural proteins in the extracellular matrix (ECM) of various tissues, including cartilage, bone, blood vessels, skin and other connective tissues, with types I, II and III making up 80–90% of the collagen in the human body.2 Cartilage contains an ECM rich in glycosaminoglycans and up to 15 types of collagens. The combination of collagens and other ECM molecules gives cartilage biomechanical properties in compression, shear and tension.3

1. Bielajew B, Hu J, Athanasiou K. Collagen: quantification, biomechanics, and role of minor subtypes in cartilage. Nature reviews Materials. 2020 Oct 2020;5(10)doi:10.1038/s41578-020-0213-1
2. Kadler K, Hill A, Canty-Laird E. Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Current opinion in cell biology. 2008 Oct 2008;20(5)doi:10.1016/j.ceb.2008.06.008
3. Huey D, Hu J, Athanasiou K. Unlike bone, cartilage regeneration remains elusive. Science (New York, NY). 11/16/2012 2012;338(6109)doi:10.1126/science.1222454

Contributor: Theofilos Karasavvidis

Connective Tissue

The matrix-continuous tissue which binds together and is the support of all the structures of the body. The predominant structural protein comprising the extracellular matrix of connective tissue is collagen.

Contributor: Myron Spector

Creeping substitution

The biologic process of osseous integration of bone graft within native bone. This is a process of bone remodeling by osteoblastic bone formation and osteoclastic resorption of the bone graft. With transplanted osteochondral allografts, the creeping substitution process is slow, beginning at the graft-host junction and moving towards the center of the allograft.

Demange M, Gomoll AH. The use of osteochondral allografts in the management of cartilage defects. Curr Rev Musculoskelet Med. 2012 Sep;5(3):229-35. doi: 10.1007/s12178-012-9132-0. PMID: 22628178; PMCID: PMC3535086.

Lai WC, Bohlen HL, Fackler NP, Wang D. Osteochondral Allografts in Knee Surgery: Narrative Review of Evidence to Date. Orthop Res Rev. 2022 Aug 11;14:263-274. doi: 10.2147/ORR.S253761. PMID: 35979427; PMCID: PMC9377395.

Contributor: Dean Wang

CTE (Cartilage tissue engineering)

Regeneration or repair of articular cartilage defects remains one of the major clinical challenges for orthopedic surgeons to treat osteoarthritic patients with minimal possibilities of reconstructed tissue degeneration at the defect site in the future. Avascular cartilage tissue possesses poor inherent regenerative potential and leads to the formation of inferior fibrocartilaginous tissues or a combination of hyaline and fibrocartilage at the defect sites ACI was considered a standard treatment involving the application of in-vitro expanded autologous chondrocytes and periosteal flaps to seal the implanted cells at the defect site. However, various challenges are associated with ACI, such as the requirement of a large number of chondrocytes which are mostly obtained through long-term 2D in-vitro expansion, generation of fibro chondrocyte due to dedifferentiation of chondrocytes, complexity of cellular implantation or hypertrophy of periosteal flap There is a great need for CTE to develop a suitable scaffold with superior biocompatibility, biodegradability, biomechanical integrity, biomimetic, and exogenous growth factors for articular cartilage tissue reconstruction.

[1] H. H, A. DC, Anionic and zwitterionic residues modulate stiffness of photo-crosslinked hydrogels and cellular behavior of encapsulated chondrocytes, ACS Biomater Sci. Eng. 4 (2018) 1843–1851.

[2] Y. AM, H. ME, P. RG, U. N, Current strategies in multiphasic scaffold design for osteochondral tissue engineering: a review, J. Biomed. Mater. Res. A 103 (2015) 2460–2481.

[3] M. Ea, G. Ah, M. Kn, H. Jc, A. Ka, Repair and tissue engineering techniques for articular cartilage, Nat. Rev. Rheumatol. 11 (2015) 21–34.

[4] S. Roberts, J. Menage, L.J. Sandell, E.H. Evans, J.B. Richardson, Immunohistochemical study of collagen types I and II and procollagen IIA in human cartilage repair tissue following autologous chondrocyte implantation, Knee 16 (2009) 398.

[5] B. Zyli ˙ nska, ´ P. Silmanowicz, A.S.-R. Treatment of articular cartilage defects: focus on tissue engineering, In Vivo 32(6) (2018) 1289–1300.

[6] H. Sh, W. Sw, H. Sc, T. Cl, C. Dc, T. Ts, Evaluation of chitosan-alginate-hyaluronate complexes modified by an RGD-containing protein as tissue-engineering scaffolds for cartilage regeneration, J. Artif. Organs 28 (2004) 693–703. 

Contributor: Arulkumar Nallakumarasamy

Cytokine

Substances secreted by cells for the purpose of cell signaling and generating immune response. Cytokines may be pro-inflammatory or anti-inflammatory depending on target cell type and the local and systemic immune state. Examples of cytokines include interferons, growth factors (i.e., vascular endothelial growth factor (VEGF), transforming growth factor(TGF)-β), and interleukins (interleukin-1α, interleukin-6). A wide range of cytokines and growth factors may also serve as chemokines.

Contributor: Austin Stone

Decellularization (also spelt Decellularisation in British English)

It is the process of removing all the cellular component of tissue, leaving the extracellular matrix (ECM) intact. The obtained ECM then used as a scaffold for tissue regeneration/ tissue engineering applications.

Contributor: Sara Ahmed Hassouna Elsayed

Demineralized Bone Matrix (DBM)

Demineralized Bone Matrix (DBM) is an osteoinductive and osteoconductive bone grafting material derived from decalcified allograft bone. The bone undergoes a process to remove the inorganic mineral content, leaving behind an organic matrix rich in collagen, growth factors, and bone morphogenetic proteins (BMPs). DBM serves as a scaffold for bone growth and repair, aiding in the regeneration of new bone tissue.

1. Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO. Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev. 2012 Sep;64(12):1063-77. doi: 10.1016/j.addr.2012.06.008. Epub 2012 Jun 21. PMID: 22728914; PMCID: PMC7103314.

2. Zhang H, Yang L, Yang XG, Wang F, Feng JT, Hua KC, Li Q, Hu YC. Demineralized Bone Matrix Carriers and their Clinical Applications: An Overview. Orthop Surg. 2019 Oct;11(5):725-737. doi: 10.1111/os.12509. Epub 2019 Sep 8. PMID: 31496049; PMCID: PMC6819172.

Contributor: Garrett Jackson

Development

The process of growth and differentiation of tissues and organs.

Contributor: Myron Spector

Disease modifying osteoarthritis drugs

A putative class of agents that aim to act on the key tissues involved in OA to prevent structural progression and therefore improve symptoms. Currently, no DMOADs have been licensed for use but a number of potential therapies are under investigation.

https://journals.sagepub.com/doi/10.1177/1759720X19864492

https://www.sciencedirect.com/science/article/abs/pii/S0165614721002637

Contributor: jingjing Gao

Drug

Small molecules which are chemically synthesized and well defined, intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.

Contributor: Myron Spector

ECM

Extracellular Matrix is the non-cellular component of tissues and organs, and consists of a variety of proteins (collagen, elastin, proteoglycans, etc.). It is integral in the morphogenesis, differentiation, and homeostasis of all tissues in the body, and its composition and organization provide each tissue with a specific set of chemical and mechanical properties that are crucial to tissue function.

Contributor: Jay Patel

Edema

Edema is swelling trapped in the interstitial tissues of the body. While edema is more common in the lower extremities, it can occur anywhere in the body. Pathophysiology can be related to rise in hydrostatic pressure or drop in oncotic pressure. There can be several causes: systemic disease, venous disease, diet, and allergic reactions.

Contributor: Dhanur Damodar

Embryology

The science of the development of the individual during the embryonic stage (2 weeks after fertilization of the ovum to the end of the eighth week) and, by extension, in several or even all preceding and subsequent stages of the life cycle.

Contributor: Myron Spector

Endochondral Ossification

Process by which long bones are developed and repaired through the formation of an intermediate cartilage template which is subsequently vascularized and mineralized, and finally, replaced by mature bone. 

Contributor: Tomas Gonzalez Fernandez

Endocrine

Refers to tissues and organs whose function is to secrete into the blood or lymph a substance (e.g., hormone) that has a specific effect on another organ or tissue.

Contributor: Myron Spector

Enthesis

The enthesis is the region where a tendon or ligament attaches to bone. This is a highly specialized tissue that presents gradients of cellular composition, collagen alignment, and mineralization to allow the dissipation of energy and smooth stress transfer between tendons/ligaments and bones.

1.Apostolakos, J., T.J. Durant, C.R. Dwyer, R.P. Russell, J.H. Weinreb, F. Alaee, K. Beitzel, M.B. McCarthy, M.P. Cote, and A.D. Mazzocca, The enthesis: a review of the tendon-to-bone insertion. Muscles, ligaments and tendons journal, 2014. 4(3): p. 333-342.

2.Bunker, D.L., V. Ilie, V. Ilie, and S. Nicklin, Tendon to bone healing and its implications for surgery. Muscles Ligaments Tendons J, 2014(2240-4554 (Print)): p. 343-50.

Contributor: Carlos Peniche

Epimorphic regeneration

Epimorphic regeneration is a process by which an entire appendage is completely restored in terms of tissue composition, structure, and functionality. This involves the formation of a blastema, a mass of hyperproliferative stem/progenitor cells that give rise to the regenerated tissues.

Londono R, Sun AX, Tuan RS, Lozito TP. TISSUE REPAIR AND EPIMORPHIC REGENERATION: AN OVERVIEW. Curr Pathobiol Rep. 2018 Mar;6(1):61-69.

Contributor: Feini Qu

Exosome

Exosomes are small extracellular vesicles released by all cell types and involved in intercellular communication, immune response as well as cell growth, fate and differentiation. Exosomes secreted by mesenchymal stem cells have shown chondroprotective effects in different preclinical studies and are currently investigated as a promising regenerative tool to treat osteoarthritis and other degenerative diseases1.

Contributor: Luca Ambrosio

Extracellular Vesicles

Extracellular vesicles (EVs) are cell-derived nanoparticles delimited by a phospholipid bilayer with key roles in intercellular communication due to the ability to carry a rich cargo of soluble factors including growth factors, DNA, micro RNAs (miRNAs), signaling peptides, metabolites, structural proteins, lipids, etc. Furthermore, the inherent stability of their lipid bilayer and the capacity to be promptly internalized by target cells render EVs a natural drug delivery system. EVs are divided into three different classes based on size, morphology, biogenesis, and content. Apoptotic bodies are the largest EVs ranging from 50 to 5000 nm in diameter, with a heterogenous morphology deriving from cell fragmentation. Microvesicles, ranging between 50 and 1000 nm, are characterized by a spherical structure and a highly variable content. Exosomes, which have been more frequently investigated for their regenerative properties, measure between 50 and 150 nm, present a typical cup shape, and hold a fundamental role in cell communication, fate, and metabolism.

• DiStefano, T.J., et al., Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations. Advanced Healthcare Materials, 2021. 11(5).
• Thery, C., et al., Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles, 2018. 7(1): p. 1535750.
• Tilotta, V., et al., Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration. Applied Sciences, 2021. 11(23).

Contributor: Luca Ambrosio

Extracorporeal shockwave Therapy (ESWT)

Extracorporeally generated shockwave therapy is a treatment using high magnitude, short duration pressure pulses which are introduced into the body without injuring the skin. They can be delivered as non-focused (radial) or as focused pressure pulses. ESWT has been in clinical use since the 1980s for lithotripsy to treat kidney stones and stones in the gallbladder or in the liver. The beneficial effect of ESWT on tissue regeneration has been demonstrated in numerous experimental and clinical studies. Nowadays ESWT is commonly used as an orthopaedic treatment option for tendon, muscle and bone regeneration.

Feichtinger X, Monforte X, Keibl C, Hercher D, Schanda J, Teuschl AH, Muschitz C, Redl H, Fialka C, Mittermayr R. Substantial Biomechanical Improvement by Extracorporeal Shockwave Therapy After Surgical Repair of Rodent Chronic Rotator Cuff Tears. Am J Sports Med. 2019 Jul;47(9):2158-2166. doi: 10.1177/0363546519854760. Epub 2019 Jun 17. PMID: 31206305.

Mittermayr R, Haffner N, Feichtinger X, Schaden W. The role of shockwaves in the enhancement of bone repair - from basic principles to clinical application. Injury. 2021 Jun;52 Suppl 2:S84-S90. doi: 10.1016/j.injury.2021.02.081. Epub 2021 Mar 2. PMID: 33714550.

Contributor: Xaver Feichtinger

Fairbank's changes

This term describes the radiological changes observed on an anteroposterior radiograph of the knee after total meniscectomy. These changes involve square condyle, peak eminences, ridging, narrowing of the joint space.

1. Fairbank, T. J. "Knee joint changes after meniscectomy." The Journal of bone and joint surgery. British volume 30.4 (1948): 664-670.

2. Krych, Aaron J., et al. "Meniscal root injuries." JAAOS-Journal of the American Academy of Orthopaedic Surgeons 28.12 (2020): 491-499.

3. Jeong, Hwa-Jae, Seung-Hee Lee, and Chun-Suk Ko. "Meniscectomy." Knee surgery & related research 24.3 (2012): 129.

Contributor: Özgür Başal

Fatty Infiltration

When a muscle has been chronically detached or denervated, the muscle belly gradually becomes infiltrated with fat. This is a distinct phenomenon from atrophy, which refers to loss of the muscle bulk, not infiltration. This is most commonly seen in chronic rotator cuff tears, or in significant suprascapular neuropathy, when the infraspinatus can become fatty infiltrated, with or without involvement of the supraspinatus. In the presence of fatty infiltration, particularly when high grade (muscle is 50% or more infiltrated with fat), rotator cuff repair is associated with worse outcomes and higher retear rates. Fatty infiltration is largely irreversible.

Contributor: Michael Amini

Femoroacetabular impingement (FAI)

Femoroacetabular impingement (FAI) is a disease in which extra bone grows along one or both of the bones that form the hip joint, causing the bones to be irregularly shaped. As a result, the bones rub against each other when the hip joint is moved. If this friction continues for a long time, it can damage the joint, causing pain and limiting activity. FAI has been established as an important cause of hip osteoarthritis (1). Today, FAI is recognized as a leading cause of hip pain in younger adults as well as degenerative arthritis in the hip (2). The estimated prevalence of FAI has varied between 10% and 25% in the population.

1.    Ganz R, Parvizi J, Beck M, et al. Femoroacetabular impingement: a cause for osteoarthritis of the hip. Clin Orthop Relat Res. 2003;417:112–120.

2.    Beck M, Kalhor M, Leunig M, Ganz R. Hip morphology influences the pattern of damage to the acetabular cartilage: femoroacetabular impingement as a cause of early osteoarthritis of the hip. J Bone Joint Surg Br. 2005;87(7):1012–1018.

3.    Jung KA, Restrepo C, Hellman M, et al. The prevalence of cam-type femoroacetabular deformity in asymptomatic adults. J Bone Joint Surg Br. 2011;93(10):1303–1307.

Contributor: Tomoyuki Kamenaga

Fibrin glue

Fibrin glue is a biological adhesive, which imitates the final stages of coagulation. The glue consists of two components - concentrated human fibrinogen, and bovine thrombin and calcium chloride - and is activated by their combination. The fibrinogen component can be obtained from fresh frozen plasma from single unit donations or can be prepared in advance of surgery from autologous blood, reducing the risk of transmission of disease and cost. It is used in multiple ways for years as a topical homeostatic, to adhere tissues together, and to seal tissue defects. It is also used as a simple promising one-step cartilage repair procedure in combination with minced cartilage.

1.    Wodzig MHH, Peters MJM, Emanuel KS, Van Hugten PPW, Wijnen W, Jutten LM, Boymans TA, Loeffen DV, Emans PJ. Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up. Cartilage. 2022 Dec;13(4):19-31. doi: 10.1177/19476035221126343. Epub 2022 Oct 28. PMID: 36305343; PMCID: PMC9924984.

2.    Brennan M. Fibrin glue. Blood Rev. 1991 Dec;5(4):240-4. doi: 10.1016/0268-960x(91)90015-5. PMID: 1782483.

3.    Silver FH, Wang MC, Pins GD. Preparation and use of fibrin glue in surgery. Biomaterials. 1995 Aug;16(12):891-903. doi: 10.1016/0142-9612(95)93113-r. PMID: 8562777.

Contributor: Stephanie Windemuth

Fibroblast

Fibroblasts comprise the main cell type of connective tissue, possessing a spindle-shaped morphology. They produce extracellular matrix responsible for maintaining structural integrity of tissue. Fibroblasts also play an important role in proliferative phase of wound healing, resulting in deposition of extracellular matrix

Ichim, T.E., O’Heeron, P. & Kesari, S. Fibroblasts as a practical alternative to mesenchymal stem cells. J Transl Med 16, 212 (2018). https://doi.org/10.1186/s12967-018-1536-1

Contributor: Teresita Gomez

Freeze-drying

Freeze-drying (FD) is a dehydration technique, which enables frozen solutions or frozen slurry products to be dried under a vacuum through sublimation.The main aim of FD is to enhance product preservation, storage life and marketing of a product by removal of water content. It is a method of drying while maintaining the original structure and activity. It is a reversible process and easily reconstitutes. Disadvantages of freeze-drying can be summarized into (i) high capital cost of equipment and cost of running equipment (energy costs), (ii) it is a batch process and (iii) it can be time-consuming when using non-optimized protocols (days). Generally, the freeze-drying cycle is divided in 3 phases: - Freezing phase: freezes both solvent and solute. This means, it immobilizes the material and defines the structure ready for drying. - Primary drying: it consists on the removal of the frozen moisture by a process of sublimation, i.e., the evaporation of ice to vapour without passing through the liquid phase. - Secondary drying: the product is further dried by a process of desorption. This step is used to control the level of final moisture (some products require more moisture than others to maintain stability).

Contributor: Pedro Diaz Payno

Growth Factor

Secreted biologically-active polypeptide that can affect cellular growth, proliferation and differentiation.

Contributor: Fabrizio Russo

H-Type Vessels

H-Type Vessels are characterized by a high expression of Endomucin (Emcn) and CD31. They couple osteogenesis to angiogenesis and are localized at the periosteum and endosteum proximal to compact bone or near the growth plate in the metaphysis. Their role in diseases such as osteoarthritis, osteoporosis and fracture healing is currently being investigated.

Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507:323–28

Lu J, Zhang H, Cai D, Zeng C, Lai P, Shao Y. et al. Positive-Feedback Regulation of Subchondral H-Type Vessel Formation by Chondrocyte Promotes Osteoarthritis Development in Mice. J Bone Miner Res. 2018;33:909–20.

Romeo SG, Alawi KM, Rodrigues J, Singh A, Kusumbe AP, Ramasamy SK. Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation. 2019; 21: 430-41

Wang L, Zhou F, Zhang P, Wang H, Qu Z, Jia P, Human type H vessels are a sensitive biomarker of bone mass. 2017; 8: e2760.

Contributor: Antonia Donat

Hyaline Cartilage

Avascular specialized connective tissue consisting of chondrocytes and a highly resilient extracellular matrix. Its cellular matrix represents more than 95% of its volume and comprises type II collagen fibrils and aggrecans, among other components. It is found in fetal skeletal tissue, epiphyseal plates, the surface of synovial joints, costal cartilages of the rib cage and respiratory system.

Contributor: Theodorakys Marín Fermín

Hyaluronic Acid

High-molecular glycosaminoglycan naturally present in cartilage extracellular matrix and in the synovial fluid. With its biochemical properties, it provides tissues with peculiar rheological and biomechanical characteristics, including shock-absorbing and lubricating features3.

Contributor: Luca Ambrosio

Hydrogel

Hydrogels are biocompatible, polymeric and hydrophilic biomaterials organized in three-dimensional networks. As they are easy to handle and widely tunable, their use as scaffolds for musculoskeletal tissue regeneration is being extensively investigated in the last decades4.

Contributor: Luca Ambrosio

Hyperplasia

The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue.

Contributor: Myron Spector

Hypertrophy

The enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells.

Contributor: Myron Spector

IDD

Intervertebral disc degeneration (IDD) is often caused by structural and biochemical changes in intervertebral discs that prompt a pathologic shift from an anabolic to catabolic state, affecting extracellular matrix production, enzyme generation, cytokine and chemokine production, neurotrophic and angiogenic factor production (1). It is the cause of around half of all LBP cases in young adults; however not all cases of IDD result in LBP (2). Although IDD prevalence increases progressively with age, IDD is common in subjects younger than 30 years old, conveying those various other factors besides age, such as excessive or uneven mechanical load, obesity, genetics, nutrition, trauma, and gender are involved (3,4,5,6,7,8,9)

(1) Bermudez-Lekerika P, Crump KB, Tseranidou S, Nüesch A, Kanelis E, Alminnawi A, Baumgartner L, Muñoz-Moya E, Compte R, Gualdi F, Alexopoulos LG, Geris L, Wuertz-Kozak K, le Maitre CL, Noailly J, Gantenbein B (2022) Immuno-modulatory efects of intervertebral disc cells. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2022.924692

(2) Baumgartner L., Wuertz-Kozak K., Le Maitre C. L., Wignall F., Richardson S. M., Hoyland J., et al. (2021c). Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research. Ijms 22, 703. 10.3390/ijms22020703

(3) Hoogendoorn W. E., van Poppel M. N. M., Bongers P. M., Koes B. W., Bouter L. M. (2000). Systematic Review of Psychosocial Factors at Work and Private Life as Risk Factors for Back Pain. Spine 25, 2114–2125. 10.1097/00007632-200008150-00017

(4) Paassilta P., Lohiniva J., Göring H. H., Perälä M., Räinä S. S., Karppinen J., et al. (2001). Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease. JAMA 285, 1843–1849. 10.1001/jama.285.14.1843

(5) Pincus T., Burton A. K., Vogel S., Field A. P. (2002). A Systematic Review of Psychological Factors as Predictors of Chronicity/disability in Prospective Cohorts of Low Back Pain. Spine 27, E109–E120. 10.1097/00007632-200203010-00017

(6) Cheung K. M. C., Karppinen J., Chan D., Ho D. W. H., Song Y.-Q., Sham P., et al. (2009). Prevalence and Pattern of Lumbar Magnetic Resonance Imaging Changes in a Population Study of One Thousand Forty-Three Individuals. Spine 34, 934–940. 10.1097/BRS.0b013e3181a01b3f

(7) Samartzis D., Karppinen J., Chan D., Luk K. D. K., Cheung K. M. C. (2012). The Association of Lumbar Intervertebral Disc Degeneration on Magnetic Resonance Imaging with Body Mass Index in Overweight and Obese Adults: a Population-Based Study. Arthritis & Rheumatism 64, 1488–1496. 10.1002/art.33462

(8) Teraguchi M., Yoshimura N., Hashizume H., Muraki S., Yamada H., Minamide A., et al. (2014). Prevalence and Distribution of Intervertebral Disc Degeneration over the Entire Spine in a Population-Based Cohort: the Wakayama Spine Study. Osteoarthr. Cartil. 22, 104–110. 10.1016/j.joca.2013.10.019

(9) Parenteau C. S., Lau E. C., Campbell I. C., Courtney A. (2021). Prevalence of Spine Degeneration Diagnosis by Type, Age, Gender, and Obesity Using Medicare Data. Sci. Rep. 11, 5389. 10.1038/s41598-021-84724-6

Contributor: Paola Bermudez Lekerika

Induced pluripotent stem (iPS) cells

Induced pluripotent stem (iPS) cells are a type of pluripotent stem cells derived from adult somatic cells that have been genetically reprogrammed to an embryonic stem (ES) cell-like state by forcing expression of certain genes and factors which are critical for maintaining the defining properties of ES cells [1]. The discovery of iPS cells allows scientists to obtain pluripotent stem cells without the use of embryos, providing a way to “de-differentiate” cells. iPS cells may be a promising cell source for treating cartilage defects.

1. Ye L, Swingen C, Zhang J. Induced pluripotent stem cells and their potential for basic and clinical sciences. Curr Cardiol Rev. 2013 Feb 1;9(1):63-72.

Contributor: Hamid Rahmatullah Bin Abd Razak

Infrapatellar fat pad stromal cells (FPSCs)

Infrapatellar fat pad stromal / stem cells (FPSCs) are a type of progenitor cell that can be isolated by the enzymatic digestion of a biopsy of infrapatellar fat pad (IFP) tissue. The anatomical location of the IFP in the knee joint and the high proportion of putative progenitor cells with chondrogenic potential found in the tissue make the IFP an ideal cell source for cartilage repair applications [1]. Culture expanded infrapatellar fat pad derived stromal cells (FPSCs) have been demonstrated to have at least comparable chondrogenic capacity to bone marrow derived stem cells (BM-MSCs) and can maintain their chondrogenic capacity in disease [2-6]. More recent studies have shown that the IFP is a significant source of perivascular stem cells that possess potent chondrogenic potential [7].

Contributor: David Browe

Interfascicular matrix (IFM)

The interfascicular matrix (IFM) makes up a continuous compartment between tendon fascicles, housing the tendon vasculature and metabolically active mural and stromal cells (1). The IFM is important for facilitating fascicle sliding during tendon loading and may be specialized for each tendon. Evidence suggests that tendon pathology may derive from alterations in the structure and composition of the IFM (2,3) and recent work has identified a unique vascular niche residing within the IFM that expands following injury(4).

1. Patel, D. et al. Structure-function specialisation of the interfascicular matrix in the human achilles tendon. Acta Biomater. 131, 381–390 (2021).

2. Thorpe, C. T. et al. The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons. J. Mech. Behav. Biomed. Mater. 52, 85–94 (2015).

3. Godinho, M. S. C., Thorpe, C. T., Greenwald, S. E. & Screen, H. R. C. Elastin is localised to the interfascicular matrix of energy storing tendons and becomes increasingly disorganised with ageing. Sci. Rep. 7, 9713 (2017).

4. Marr, N. et al. The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations. Front. Cell Dev. Biol. 10, (2022).

Contributor: Jessica Ackerman

Intervertebral Disc

The intervertebral disc is a complex, avascular organ located between the vertebrae. It is composed of three specialized tissues: the nucleus pulposus, the annulus fibrosus and the cartilaginous endplates, connecting the disc with the contiguous vertebral structures. The annulus fibrosus constitutes the external part of the disc and surrounds the nucleus pulposus, which provides such organ with its unique biological and biomechanical properties2.

Contributor: Luca Ambrosio

Intervertebral Disc Herniation

During intervertebral disc degeneration, the annulus fibrosus tissue is compromised with alterations in extracellular matrix content and organization (1). Consequently, this annulus fibrosus failure impairs the nucleus pulposus integrity and leads to intervertebral disc herniation (2). This process can compress the closest nerve roots consequently resulting in pain. (3)

(1) Castro AL, et al. Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation. Arthritis Research and Therapy, 2022.

(2) Chu G, et al. Strategies for annulus fibrosus regeneration: from biological therapies to tissue engineering. Frontiers in Bioengineering and Biotechnology, 2018.
(3) Blamoutier A, et al. Nerve root compression by lumbar disc herniation. Orthopaedics & Traumatology: Surgery & Research, 2019.

Contributor: Ana Luísa Castro

Intramembranous Ossification

Intramembranous ossification is responsible for the embryonic development of bones of the cranium and parts of the clavicle. The process of intramembranous ossification involves the direct differentiation of mesenchymal cell condensates into bone, without the presence of a cartilaginous intermediate(1, 2). Bones formed via intramembranous ossification expression the master transcription factor of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and lack expression of master chondrogenic transcription factor SRY-Box transcription factor 9 (Sox9) (3). Bone regeneration following injury is a post-natal recapitulation of embryonic development (4). In this manner, skeletal fracture healing occurs as a combination of direct, intramembranous ossification and endochondral ossification, which involves a cartilaginous intermediate.

1. A. D. Berendsen, B. R. Olsen, Bone development. Bone 80, 14-18 (2015).

2. G. Karsenty, The complexities of skeletal biology. Nature 423, 316-318 (2003).

3. B. F. Eames, P. T. Sharpe, J. A. Helms, Hierarchy revealed in the specification of three skeletal fates by Sox9 and Runx2. Dev Biol 274, 188-200 (2004).

4. A. Salhotra, H. N. Shah, B. Levi, M. T. Longaker, Mechanisms of bone development and repair. Nat Rev Mol Cell Biol 21, 696-711 (2020)

Contributor: Joseph Panos

Kartogenin

Kartogenin (KGN) is a small heterocyclic molecule that has been described to effectively enhance the chondrogenic differentiation of human bone marrow MSC (hBMSC), exhibit chondroprotective effects in vitro, and reduce cartilage degeneration after intra-articular injection in OA mouse models. Moreover, as it is a highly stable small molecule, KGN can be stored and transported at room temperature, which is an obvious superiority over peptide growth factors [1]. KGN mechanism of function was first reported by Jonson et al [2]. KGN functions by interacting with the actin-binding protein filamin A, disrupting its balance with the transcription factor core-binding factor β (CBFβ). CBFβ enters the nucleus and interacts with RUNX1 to form the CBFβ-RUNX1 complex that activates the transcription of chondrogenesis-related proteins and enhances cartilage ECM synthesis. In recent years, several groups have developed biomaterial platforms to promote the sustained release of KGN towards improved cartilage and osteochondral regeneration strategies [3-6].

1. Im, G. I. (2018). Application of kartogenin for musculoskeletal regeneration. Journal of Biomedical Materials Research Part A, 106(4), 1141-1148.

2. Johnson, K., Zhu, S., Tremblay, M. S., Payette, J. N., Wang, J., Bouchez, L. C., Meeusen, S., Althage, A., Cho, C. Y., Wu, X., & Schultz, P. G. (2012). A stem cell–based approach to cartilage repair. Science, 336(6082), 717-721.

3. Cai, G., Liu, W., He, Y., Huang, J., Duan, L., Xiong, J., Liu, L., & Wang, D. (2019). Recent advances in kartogenin for cartilage regeneration. Journal of drug targeting, 27(1), 28-32.

4. Shi, D., Xu, X., Ye, Y., Song, K., Cheng, Y., Di, J., Hu, Q., Li, J., Ju, H., Jiang, Q., & Gu, Z. (2016). Photo-cross-linked scaffold with kartogenin-encapsulated nanoparticles for cartilage regeneration. ACS nano, 10(1), 1292-1299.

5. Kang, M. L., Ko, J. Y., Kim, J. E., & Im, G. I. (2014). Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration. Biomaterials, 35(37), 9984-9994.

6. Silva, J. C., Udangawa, R. N., Chen, J., Mancinelli, C. D., Garrudo, F. F., Mikael, P. E., Cabral, J. M. S., Ferreira, F. C., & Linhardt, R. J. (2020). Kartogenin-loaded coaxial PGS/PCL aligned nanofibers for cartilage tissue engineering. Materials Science and Engineering: C, 107, 110291.

Contributor: João C. Silva

Kartogenin

Kartogenin (KGN) is a small heterocyclic molecule that has been described to effectively enhance the chondrogenic differentiation of human bone marrow MSC (hBMSC), exhibit chondroprotective effects in vitro, and reduce cartilage degeneration after intra-articular injection in OA mouse models. Moreover, as it is a highly stable small molecule, KGN can be stored and transported at room temperature, which is an obvious superiority over peptide growth factors [1]. KGN mechanism of function was first reported by Jonson et al [2]. KGN functions by interacting with the actin-binding protein filamin A, disrupting its balance with the transcription factor core-binding factor β (CBFβ). CBFβ enters the nucleus and interacts with RUNX1 to form the CBFβ-RUNX1 complex that activates the transcription of chondrogenesis-related proteins and enhances cartilage ECM synthesis. In recent years, several groups have developed biomaterial platforms to promote the sustained release of KGN towards improved cartilage and osteochondral regeneration strategies [3-6].

1. Im, G. I. (2018). Application of kartogenin for musculoskeletal regeneration. Journal of Biomedical Materials Research Part A, 106(4), 1141-1148.

2. Johnson, K., Zhu, S., Tremblay, M. S., Payette, J. N., Wang, J., Bouchez, L. C., Meeusen, S., Althage, A., Cho, C. Y., Wu, X., & Schultz, P. G. (2012). A stem cell–based approach to cartilage repair. Science, 336(6082), 717-721.

3. Cai, G., Liu, W., He, Y., Huang, J., Duan, L., Xiong, J., Liu, L., & Wang, D. (2019). Recent advances in kartogenin for cartilage regeneration. Journal of drug targeting, 27(1), 28-32.

4. Shi, D., Xu, X., Ye, Y., Song, K., Cheng, Y., Di, J., Hu, Q., Li, J., Ju, H., Jiang, Q., & Gu, Z. (2016). Photo-cross-linked scaffold with kartogenin-encapsulated nanoparticles for cartilage regeneration. ACS nano, 10(1), 1292-1299.

5. Kang, M. L., Ko, J. Y., Kim, J. E., & Im, G. I. (2014). Intra-articular delivery of kartogenin-conjugated chitosan nano/microparticles for cartilage regeneration. Biomaterials, 35(37), 9984-9994.

6. Silva, J. C., Udangawa, R. N., Chen, J., Mancinelli, C. D., Garrudo, F. F., Mikael, P. E., Cabral, J. M. S., Ferreira, F. C., & Linhardt, R. J. (2020). Kartogenin-loaded coaxial PGS/PCL aligned nanofibers for cartilage tissue engineering. Materials Science and Engineering: C, 107, 110291.

Contributor: João C. Silva

KOOS

The Knee Injury and Osteoarthritis Outcome Score (KOOS) is one of the most used scores in the assessment of knee injuries and associated problems over short- and long-term follow-up. It is used at patients with posttraumatic osteoarthritis (PTOA) and knee injuries (e.g., anterior cruciate ligament-, meniscal-, or chondral injury). KOOS outlines five domains: pain frequency and severity, symptoms, activities of daily living (ADL), sports and knee-related problems, and quality of life (QOL). The questionnaire includes 42 items across 5 subscales, which are rated between 0 and 4. A score (100=no knee problems, 0=extreme knee problems) is calculated for each dimension. Completing the KOOS questionnaire will take 10 minutes.

·        Collins, Natalie J et al. “Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS).” Arthritis care & research vol. 63 Suppl 11,0 11 (2011): S208-28. doi:10.1002/acr.20632

Contributor: Nikolaus Kraml

K-SES

The K-SES (Knee Self-Efficacy Scale) is a Swedish scoring tool initially described by Thomeé et al. (1) to measure self-efficacy in patients with anterior cruciate ligament injuries. Self-efficacy is considered to be of major importance for rehabilitation outcomes after sports-related injuries. The K-SES was later cross-culturally adapted into English by Ezzat et al. (2)

1. Thomeé P, Währborg P, Börjesson M, Thomeé R, Eriksson BI, Karlsson J. A new instrument for measuring self-efficacy in patients with an anterior cruciate ligament injury. Scand J Med Sci Sports. 2006 Jun;16(3):181-7. doi: 10.1111/j.1600-0838.2005.00472.x. PMID: 16643196.
2. Ezzat AM, Whittaker JL, Brussoni M, Mâsse LC, Emery CA. The English Knee Self-Efficacy Scale is a valid and reliable measure for knee-specific self-efficacy in individuals with a sport-related knee injury in the past 5 years. Knee Surg Sports Traumatol Arthrosc. 2021 Feb;29(2):616-626. doi: 10.1007/s00167-020-05974-x. Epub 2020 Apr 17. PMID: 32303799.
   

Contributor: Lorenz Pichler

Lateral Extra-articular Tenodesis

A surgical procedure, usually performed in combination with ACL reconstruction, during which a strand of the iliotibial band is passed beneath the lateral collateral ligament and stabilized in the femur to reduce internal rotation of the tibia.

https://doi.org/10.1016/j.jisako.2023.03.001

Contributor: Vasileios Mitrousias

Lateral Femoral Condyle Index (LFCI)

The Lateral Femoral Condyle Index (LFCI) also called Lateral Femoral Condyle Ratio (LFCR) is an index used to describe the bony morphology of the lateral femoral condyle by putting the posterior femoral condylar depth in relation to the total condylar length. It can be measured either on lateral knee radiographs or on knee MRI scans, using two circles (Picture 1, Copyright Hodel et al). An increased LFCI has been associated with an increased risk of ACL rupture mostly likely by allowing the knee an increased pivot shift.

• Hodel S, Kabelitz M, Tondelli T, Vlachopoulos L, Sutter R, Fucentese SF. Introducing the Lateral Femoral Condyle Index as a Risk Factor for Anterior Cruciate Ligament Injury. Am J Sports Med. 2019 Aug;47(10):2420-2426. doi: 10.1177/0363546519858612. Epub 2019 Jul 11. PMID: 31295005

• Pfeiffer TR, Burnham JM, Hughes JD, Kanakamedala AC, Herbst E, Popchak A, Shafizadeh S, Irrgang JJ, Debski RE, Musahl V. An Increased Lateral Femoral Condyle Ratio Is a Risk Factor for Anterior Cruciate Ligament Injury. J Bone Joint Surg Am. 2018 May 16;100(10):857-864. doi: 10.2106/JBJS.17.01011. PMID: 29762281.

Contributor: Lorenz Pichler

Leucine-rich repeat-containing G-protein (LGR6)

Leucine-rich repeat-containing G-protein coupled receptor 6 is a protein encoded by the LGR6 gene. Lgr6 is a non-canonical GPCR often studied in the context of WNT signaling when bound to R-Spondins; however, its precise mechanism of action in the bone is not well defined. Several studies have linked Lgr6 to being important for osteogenic processes and is associated with skeletal stem and progenitor cells.

Contributor: Justin King

Lift, drill, fill and fix

Lift, drill, fill and fix (LDFF) is an surgical procedure to treat osteochondral defects of the talus. During the procedure, an arthroscopic approach allows minimal-invasive therapy in which fixable lesions can be treated. It can also be performed in an open manner, via an distal tibial osteotomy or an arthrotomy. First the lesion is being lifted in order to allow microfractures to be made. This should stimulate revascularization of the sclerotic area. After this, cancellous bone (from for example the distal tibia) is being transported to the defect and the flap that was lifted is being fixated back to its location with a screw. Both the arthroscopic and the open approach seem to be effective treatment options. The arthroscopic approach shows a significant improvements in the NRS (running, walking and ret) and in the FAOS. Additionally, the subchondral bone plate restores significantly superior in comparison with arthroscopic bone marrow stimulation. Concerning the open approach, it has been shown to receive good outcomes after failed conservative treatment in children. More results on both the open technique will follow soon.

1. Kerkhoffs, G. M., Reilingh, M. L., Gerards, R. M., & de Leeuw, P. A. (2016). Lift, drill, fill and fix (LDFF): a new arthroscopic treatment for talar osteochondral defects. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 24(4), 1265–1271. https://doi.org/10.1007/s00167-014-3057-7
2. Lambers, K., Dahmen, J., Reilingh, M. L., van Bergen, C., Stufkens, S., & Kerkhoffs, G. (2020). Arthroscopic lift, drill, fill and fix (LDFF) is an effective treatment option for primary talar osteochondral defects. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 28(1), 141–147. https://doi.org/10.1007/s00167-019-05687-w
3. Rikken, Q., Dahmen, J., Stufkens, S. A., & Kerkhoffs, G. (2022). Long-Term Clinical Results of Arthroscopic Lift-Drill-Fill and Fixation (LDFF) Treatment for Osteochondral Lesions of the Talus. Foot & ankle orthopaedics, 7(1), 2473011421S00416. https://doi.org/10.1177/2473011421S00416
4. Reilingh, M. L., Lambers, K., Dahmen, J., Opdam, K., & Kerkhoffs, G. (2018). The subchondral bone healing after fixation of an osteochondral talar defect is superior in comparison with microfracture. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 26(7), 2177–2182. https://doi.org/10.1007/s00167-017-4654-z
5. Reilingh, M. L., Kerkhoffs, G. M., Telkamp, C. J., Struijs, P. A., & van Dijk, C. N. (2014). Treatment of osteochondral defects of the talus in children. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA, 22(9), 2243–2249. https://doi.org/10.1007/s00167-013-2685-7
6. 
   
   

Contributor: Jari Dahmen

Ligament

A band of strong yet pliable fibrous connective tissue between two bones that typically provides stability to a joint.

Contributor: Justin Arner

LMORT

LMORT is an acronym used by Krych et al. to describe a posterior horn lateral meniscal oblique radial tear, which is one of the most commonly identified lateral meniscal injury associated with an acute anterior cruciate ligament (ACL) disruption.2 These have been reported in as many as 12% of acute ACL reconstructions and can be difficult to recognize on magnetic resonance imaging (MRI).1 These tears are a distinct entity from tears of the posterior root of the lateral meniscus, and have been classified by Krych et al. into types 1 through 4 with treatment strategies ranging from partial meniscectomy to transtibial repair to primarily suture repair.2

1. Daniel AV, Krych AJ, Smith PA. The Lateral Meniscus Oblique Radial Tear (LMORT). Curr Rev Musculoskelet Med. 2023;16(7):306-315.

2. Krych AJ, LaPrade MD, Cook CS, et al. Lateral Meniscal Oblique Radial Tears Are Common With ACL Injury: A Classification System Based on Arthroscopic Tear Patterns in 600 Consecutive Patients. Orthopaedic Journal of Sports Medicine. 2020;8(5):232596712092173.

Contributor: William Johns

Lubricin

Lubricin is chondrocyte-secreted glycoprotein that primarily conducts boundary lubrication between joint surfaces. It is also known as superficial zone protein and is attributed with many functions relevant to its location in the superficial zone of articular cartilage, including anti-proliferative effects and inhibiting protein or cell adhesion.

1. Lee, Y., Choi, J. & Hwang, N.S. Regulation of lubricin for functional cartilage tissue regeneration: a review. Biomater Res 22, 9 (2018). https://doi.org/10.1186/s40824-018-0118-x

2. Swann DA, Silver FH, Slayter HS, Stafford W, Shore E. The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids. Biochem J. 1985;225:195-201.

3.Roberts S, Menage J, Flannery CR, Richardson JB. Lubricin: Its Presence in Repair Cartilage following Treatment with Autologous Chondrocyte Implantation. Cartilage. 2010 Oct;1(4):298-305. doi: 10.1177/1947603510370156. PMID: 26069560; PMCID: PMC4297061.

Contributor: Jonathan McKeeman

MACI

Matrix-induced Autologous Chondrocyte Implantation is 2-step cell-based technique for the treatment of focal cartilage lesions in which the cultured chondrocytes are delivered on a preseeded collagen membrane.

Contributor: LEONARDO CAVINATTO

Marrow Stimulation

Biologically regulated marrow stimulation is when a microfracture procedure is performed in conjunction with administration of an angiotensin receptor blocker. Method to improve microfracture aiming for a potentially more anatomic articular cartilage rather than fibrocartilage.

Contributor: Teresa Hall

MAT

Meniscal Allograft Transplantation is a type of surgery, for selected symptomatic and relatively young (<50 years of age) patients with meniscal deficiency. It involves replacing missing or damaged meniscus with a meniscus from a cadaver donor. MATs have been shown to have good-to-excellent results, with a measurable decrease in pain and increase in activity level in properly selected symptomatic patients. Outcomes in meniscus allograft transplantation are favorable, with reported significant improvements in clinical outcome and low failures in short- and midterm follow-up studies.

1. Gilat R, Cole BJ. Meniscal Allograft Transplantation: Indications, Techniques, Outcomes. Arthroscopy. 2020 Apr;36(4):938-939
2. Southworth TM, Naveen NB, Tauro TM, Chahla J, Cole BJ. Meniscal Allograft Transplants. Clin Sports Med. 2020 Jan;39(1):93-123
3. Cole BJ, Carter TR, Rodeo SA. Allograft meniscal transplantation: background, techniques, and results. Instructional Course Lectures. 2003 ;52:383-396. 

Contributor: Ron Gilat

Mechanobiology

Mechanobiology is the study of how mechanical forces interact with and affect biological systems such as cells and tissues [1,2]. In tissue engineering, it is critical to design repair tissues or scaffolds to fall within given mechanical thresholds of native tissues to ensure that the replacement can meet certain functional demands [1]. In cartilage tissue engineering it is important to consider the complex composition of the extracellular matrix (ECM) and the unique viscoelastic properties of the tissue when designing scaffolds or replacements [3] as these play critical roles in generating secondary biophysical signals, contributing to tissue maintenance and health [1]. Other work focused on the whole joint mechanobiology details the importance of understanding mechanical forces and how they affect tissue signaling in meniscus [4], tendon [5], and bone [6]. Future directions in the field are aimed at developing therapeutics using our knowledge of mechanical drivers of disease pathogenesis in cells and tissues [7].

[1] Guilak F, Butler DL, Goldstein SA, Baaijens FP. Biomechanics and mechanobiology in functional tissue engineering. J Biomech. 2014 Jun 27;47(9):1933-40. doi: 10.1016/j.jbiomech.2014.04.019. Epub 2014 Apr 26. PMID: 24818797; PMCID: PMC4051419.

[2] Lim CT, Bershadsky A, Sheetz MP. Mechanobiology. J R Soc Interface. 2010 Jun 6;7 Suppl 3(Suppl 3):S291-3. doi: 10.1098/rsif.2010.0150.focus. Epub 2010 Apr 7. PMID: 20375041; PMCID: PMC2943884.

[3] Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health. 2009 Nov;1(6):461-8. doi: 10.1177/1941738109350438. PMID: 23015907; PMCID: PMC3445147.

[4] Amy L. McNulty, Farshid Guilak, Mechanobiology of the meniscus, Journal of Biomechanics, Volume 48, Issue 8, 2015, Pages 1469-1478, ISSN 0021-9290, https://doi.org/10.1016/j.jbiomech.2015.02.008.

[5] Lavagnino, M., Wall, M.E., Little, D., Banes, A.J., Guilak, F. and Arnoczky, S.P. (2015), Tendon mechanobiology: Current knowledge and future research opportunities. J. Orthop. Res., 33: 813-822. https://doi.org/10.1002/jor.22871

[6] Iolascon, G., Resmini, G. & Tarantino, U. Mechanobiology of bone. Aging Clin Exp Res 25 (Suppl 1), 3–7 (2013). https://doi.org/10.1007/s40520-013-0101-2

[7] Robert J Nims, Lara Pferdehirt, Farshid Guilak, Mechanogenetics: harnessing mechanobiology for cellular engineering, Current Opinion in Biotechnology, Volume 73, 2022, Pages 374-379, ISSN 0958-1669, https://doi.org/10.1016/j.copbio.2021.09.011.

Contributor: Erica Ely

Medical Device

An implant intended: 1) for use in the cure, mitigation, treatment, or prevention of disease, in man or other animals; and 2) to affect the structure or any function of the body.

Contributor: Myron Spector

Meniscal Comma Sign

The meniscal “comma sign” is a complex, displaced parrot beak flap tear found in the meniscotibial recess, which bears its name due to the comma-shaped appearance it takes on in preoperative magnetic resonance imaging (MRI). This pathology is believed to originate as a smaller, radial tear of the mid-body, which propagates peripherally to create a flap, which subsequently becomes engaged beneath the medial collateral ligament (MCL), thus serving as a significant pain generator. Arthroscopically, these tears can be difficult to recognize due to the displacement of the flap beneath the meniscus, and a high degree of suspicion is needed by an astute arthroscopist in order to recognize, exposure, and properly manage this meniscal pathology

https://doi.org/10.3928/01477447-20180501-01

Contributor: William Johns

Meniscal Repair

Traumatic meniscus tears are common knee injuries in athletes. Τhe treatment strategy for meniscal tears is currently focused on meniscal preservation. Meniscal repair techniques have significantly advanced, from open to arthroscopic-assisted and all-arthroscopic repairs. Depending on the type and location of the tear, the meniscus may be repaired using outside-in, inside-out, and all-inside meniscal repair techniques. Compared with meniscectomy, successful meniscal repair prevents articular cartilage degeneration and leads to better patient-reported outcome scores. The mid-term outcome of arthroscopic-assisted or all-inside meniscal repair has been good to excellent (from 64 to 91%). Traumatic meniscus tears are usually accompanied with a torn ACL. In athletes with a meniscus tear, either isolated or accompanying an ACL injury, meniscal repair is associated with a 90% return to sport rate and high postoperative activity level.

Contributor: Trifon Totlis

Meniscus

A cresent-shaped (“semi-lunar”) structure found in the medial and lateral compartments of the knee between the femur and the tibia. The meniscus is comprised of fibrocartilaginous tissue with some hyaline cartilage in the tapered portion of the structure. The meniscus aids in joint articulation by distributing friction and reactive joint forces. The most common injury to the meniscus is a tear, and is often treated with (suture repair) surgery to attempt to preserve function.

Contributor: Jocelyn Compton

Microencapsulation

The process of encapsulating cells or biological factors in spheres/beads with micrometer-scale diameters. After fabrication, these spheres/beads are referred to as microspheres or microbeads. Natural and synthetic polymers are commonly used for microencapsulation. The choice of material allows researchers to control numerous properties of resultant microspheres/microbeads (e.g., degradation, transport, mechanical moduli, etc.).

Contributor: Christopher Panebianco

Microfracture

Arthroscopic procedure used to treat traumatic and degenerative cartilage defects. A microfracture awl is used to make multiple perforations placed 3–4 mm apart into the subchondral bone plate and exposing the subchondral bone marrow which creates a blood clot in the chondral defect causing the recruitment of mesenchymal stem and vascular cells that heal the defect with a fibrocartilaginous scar.

Contributor: Erick Gutierrez Cota

Minced Cartilage Implantation (MCI)

Minced Cartilage Implantation is a one-step autologous cartilage regenerative method. Cartilage fragments are harvested from the defect edge or non-weight bearing regions of the knee joint. In a next step, cartilage fragments are particulated by a scalpel or designed mincing device in small fragments (<1mm³) [1]. Mincing enlarges the surface of cartilage fragments and provides an activating stimulus of chondrocyte proliferation and differentiation [2]. Minced cartilage can be mixed with fibrin glue and platelet rich plasma (PRP) for fixation and chondrogenic stimulation. Finally, minced cartilage is re-implanted into the defect and can be additionally fixated by a membrane [3]. The whole procedure can be performed via arthrotomy or arthroscopically [4].

Contributor: Robert Ossendorff

MSC

Originally defined as Mesenchymal Stem Cells (MSCs; and also Marrow Stem Cells), the same cells are now called Medicinal Signaling Cells (MSCs). The term medicinal signaling cells may more accurately reflect that the Mesenchymal Stem Cells can be induced to differentiate in culture, but have not yet been found to do so in vivo. The name was changed in 2010 when Arnold Caplan urged to change the name of MSCs to Medicinal Signaling Cells on the basis of findings that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative), i.e., these cells synthesize therapeutic agents in situ that are medicinal. It is the patient’s own site-specific and tissue-specific resident stem cells that construct the new tissue. The supposition is that this process can be stimulated by the bioactive factors secreted by exogenously supplied MSCs. Key to this new understanding is that MSCs are not acting as “stem cells,” but rather as Medicinal Signaling Cells releasing therapeutic agents.

Contributor: Camila Kaleka

Nonunion

Nonunion occurs when there is a stoppage to the normal bone repair process of a fracture. This is commonly defined as a fracture that has persisted for 3 months with no sign of healing. Nonunion is most commonly due to infection, malreduction, insufficient immobilisation, or inadequate vascular supply to the fracture site, and may be due to a combination of factors. Types of nonunion include septic (secondary to infection), atrophic, oligotrophic, or hypertrophic nonunion. Hypertrophic nonunions feature abundant callous formation without bridging bone, and typically occur in fractures with adequate vascular supply but inadequate stabilisation; whereas atrophic nonunions have scanty callous formation, and commonly result from inadequate vascular supply. Also referred to as fibrous union or pseudarthrosis: fibrous tissue and/or synovium fills the gap between the bone ends depending on their relative movement.

Contributor: Thomas Williamson

Organ

Two or more tissues combined to form a larger functional unit.

Contributor: Myron Spector

Orthobiologics

An umbrella term for biologically derived materials, such as platelet-rich plasma (PRP), adipose-derived mesenchymal stem cells, and bone marrow concentrate, that promote healing and regeneration of musculoskeletal tissues. The term, “biologics,” generally refers to products of cells and cells themselves.

Contributor: Deborah Pacik

Orthoregeneration

A solution for orthopedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include: drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli.

Contributor: Myron Spector

Osseointegration

1. The direct, structural and functional connection between bone and the surface of a load-bearing implant. 2. The achievement of permanent stability of an implant with bone, histologically confirmed with the initiation of osteogenesis and formation of young bone on the grafted implant

Contributor: Bryson Kemler

Osteoarthritis

A degenerative joint disease that affects over 200 million people worldwide, mostly the aging population. It is characterized by joint pain, swelling and the eventual mechanical and molecular breakdown of the articular joints. The early stages include loss of cartilage organization and proteoglycan degradation and it is followed by complete wear down of cartilage, meniscus, and hypomineralization of the subchondral bone. Current therapies rely on symptomatic treatment and in advanced cases, total joint replacement.

Contributor: Maria Cruz

Osteoblast

Osteoblasts are active bone forming cells that derive from the mesenchymal stem cells of the bone marrow. They produce the collagenous and noncollagenous proteins that constitute the matrix of the newly formed bone and are responsible for mineralization of the matrix or osteoid after a period of maturation that lasts approximately 20 days

Contributor: Teresita Gomez

Osteochondral Allograft Transplantation

Fresh osteochondral allograft (OCA) transplantation has been used for the treatment of osteochondral defects for many decades. This surgical procedure is indicated for many pathologies in the knee joint such as osteochondritis dissecans, osteonecrosis, femoral and tibial posttraumatic defects. OCAs have been shown to restore the osteochondral unit and have good or excellent objective and subjective outcomes in long-term follow-up.

Contributor: Guilherme Gracitelli

Osteochondral Autograft Transplantation

The indication for this treatment is generally a cartilage lesion area within approximately 2–4 cm2. This technique involves harvesting autologous osteochondral plugs from the femo­ral condyle and/or trochlea and transplanting them into the cartilage defect. Ultimately, the defect is filled with pieces of harvested hyaline cartilage and the underlying subchondral bone.

Contributor: Takahiro Ogura

Osteochondral Defect

A full thickness cartilage or chondral defect that extends into the subchondral bone, a mineralized and vascularized tissue beneath articular cartilage. These defects may form as a result of an injury, or disease such as Osteochondritis Dessicans (OCD). As potential therapeutics, various biomaterials-based approaches look to replace or regenerate the entire osteochondral unit.

Contributor: Hannah Zlotnick

Osteochondral lesion

Osteochondral lesion refers to a defect in the articular cartilage of a joint and underlying subchondral bone that can cause pain and debilitation in joints. Left untreated such lesions lead to the onset of osteoarthritis.

Contributor: Josephine Luk

Osteochondritis Dissecans

A joint disorder of the bone and cartilage that develops as a result of inadequate blood supply, causing a fragment of bone and cartilage to separate from its surrounding region. It primarily occurs in children and adolescents. Treatments depend on the severity of the separation. In early stages, nonoperative treatments such as a period of non-weight bearing may be successful. In more advanced stages, surgical treatments ranging from arthroscopic drilling of intact lesions, repair of the osteochondral flap with pins or screws, or replacement of the lesion with advanced cartilage restoration techniques may be required.

Contributor: Joseph Liu

Osteocyte

Osteocyte is the most abundant cell type in cortical bone. It plays an important role in bone remodeling. Its functions include 1) mechano-sensing; 2) transduction of signals; 3) coordinates osteoblasts and osteoclasts activities; and 4) production of RANKL and Sclerostin. Elongated dendrites of osteocytes will form lacuno-canalicular network that facilitate signal transmission.

1. Dallas SL et al, Endocr Rev. 2013

2. H Hemmatian et al, Curr. Osteoporos Rep, 2017

Contributor: Meng Chen Michelle Li

Osteogenesis

Osteogenesis is a bone development and formation process of laying down new bone materials. The bone formation process composed by stimulation of mesenchymal stem cells (MSCs) differentiation into osteoblast, and further osteocyte. Osteogenesis is also synonymous with bone tissue formation.

Contributor: Lu Feng

Osteogenesis imperfecta

Osteogenesis imperfecta is a genetic disorder causing a decreased amount of type I collagen, one of the main components in bone [1, 2]. The large majority of genetic mutations occur in the COL1A1 or COL1A2 genes [3-5]. The decreased amount of collagen can result from either a decreased amount of collagen secretion, or due to the production of abnormal collagen. The decreased amount of type I collagen causes an insufficient production of osteoid, and abnormal bone remodeling. Clinically, patients present with bone fragility, frequent bone fractures, ligamentous laxity, short stature, scoliosis, codfish vertebrae, basilar invagination, olecranon apophyseal avulsion fractures, coxa vara, and congenital anterolateral radial head dislocations. Non-orthopedic signs and symptoms include blue sclera, dysmorphic and triangular shaped facies, hearing loss, brownish opalescent teeth, hypermetabolism, thin skin, mitral valve prolapse, and aortic regurgitation [1, 2, 4, 6-8].

Contributor: Ava Brozovich

Osteoimmunomodulation

Osteoimmunomodulation is a concept which highlights the role of the immune response in osteogenesis and bone healing. The bone healing process is divided into four major phases that include: the inflammatory phase, fibrocartilaginous callus formation, bony callus formation and bone remodelling. During the inflammatory stage, macrophages undergo polarization to either pro- (M1) or anti- (M2) inflammatory phenotype releasing a wide range of molecules, and generating a unique osteoimmune environment which influences the behaviour of bone cells. The release of chemoattractants and cytokines by polarizing macrophages regulates both osteoclastogenic and osteogenic processes.

J.M. Sadowska, M.P. Ginebra, Inflammation and biomaterials: Role of the immune response in bone regeneration by inorganic scaffolds, Journal of Materials Chemistry B (2020), 8: 9404-9427

Contributor: Joanna Sadowska

Osteomyelitis

Defined by Lew and Waldvogel in 1997, osteomyelitis is a severe bone infection characterised by the inflammatory destruction of bone(1). Primarily caused by Staphylococcus aureus, bone infection can occur secondary to large trauma, implantation of foreign material, or from circulation of pathogens within the body(2). The incidence of osteomyelitis depends greatly on co-morbidities such as diabetes, obesity, and smoking, and depending on the type of fracture or joint replacement. Treatment for osteomyelitis traditionally requires the use of broad-spectrum systematic antibiotics, which if insufficient, necessities surgical debridement followed by the use of external or internal fixation and/or bone graft substitutes (either autograph, allographs, or tissue engineered bone replacements).

1. Lew DP, Waldvogel FA. Osteomyelitis. New England Journal of Medicine. 1997 Apr 3;336(14):999–1007.

2. Sadowska JM, Genoud KJ, Kelly DJ, O’Brien FJ. Bone biomaterials for overcoming antimicrobial resistance: Advances in non-antibiotic antimicrobial approaches for regeneration of infected osseous tissue. Materials Today. 2021 Jun 1;46:136–54.

Contributor: Katelyn Genoud

Osteoporosis

Age related decrease in bone mass more common in women predisposing to fragility fractures.

Contributor: Marina Rodriguez

Osteotomy

To surgically cut a bone and/or remove a piece of bone. An osteotomy can be performed to shift the mechanical axis of an extremity. This has an impact on regenerative procedures of the joint. High Tibial Osteotomy is a technique to cut the tibia bone to offload the medial or lateral compartment of the knee by shifting the mechanical axis of the leg. It is most commonly used to shift the mechanical axis of the lower limb from the medial compartment laterally, decreasing the medial compartment contact pressure, and contact area. The osteotomy may be an opening wedge where the bone is cut and held open (opening wedge) or a closing wedge in which a wedge of bone is removed. It can be used in conjunction with soft tissue procedures (e.g. cartilage or meniscus) to restore function of the knee. Distal Femoral Osteotomy is a technique to cut the femur bone to offload the medial or lateral compartment of the knee by shifting the mechanical axis of the leg. It is most commonly used to shift the mechanical axis of the lower limb from the lateral compartment medially, decreasing the lateral compartment contact pressure, and contact area. The osteotomy may be an opening wedge where the bone is cut and held open (opening wedge) or a closing wedge in which a wedge of bone is removed. It can be used in conjunction with soft tissue procedures (e.g. cartilage or meniscus) to restore function of the knee.

Contributor: Brian Lau

Oswestry Disability Index (ODI)

The Oswestry Disability Index (ODI) was developed in 1980 using interviews with low back pain patients (1). Since then, the version has been modified several times. The ODI is now a widely used questionnaire for assessing the functional status and quality-of-life impairment in patients with low back pain in research and clinical settings. The ODI includes 10 items and assesses the functional status and quality-of-life impairment in patients with low back pain. The index asks about functional limitations in various activities of daily living. Among others, sexual life (optional), pain intensity, personal care, walking, lifting, sitting, sleeping, and social life are assessed by the patient. In addition, the questionnaire has been adapted and validated for many different languages (including German, French, Chinese, Brazilian Portuguese, Arabic, Turkish, Polish). Completion of the questionnaire takes approximately 3-5 minutes (1). Each question can be answered on a scale of 0-5, where a 5 means maximum impairment. A sum is formed from the points given, which is then divided by the maximum value (50 points). If only one question remains unanswered, the maximum value drops accordingly to 45 points, and the score can be evaluated as usual. The calculated value is multiplied by 100 to arrive at a score in percentage points. Interpretation of the score (1): 0 - 20 %: mild disability; 21 - 40 %: moderate disability; 41 - 60 %: severe disability; 61 - 80 %: crippled; 81 - 100 %: bed-bound or exaggeration of symptoms

Contributor: Babak Saravi

Paracrine

Denoting influence of one cell on other cells in the vicinity.

Contributor: Myron Spector

Particulated Juvenile Cartilage Implant (PJCI)

Particulated Juvenile Cartilage Implant (PJCI) is a cartilage restorative technique used for the repair of articular cartilage damage. Juvenil cartilage obtained from a donor usually not older then 13 years of age is minced in small pieces, implanted into the defect, and usually fixed with fibrin glue. The advantages of the PJAC is the single-staged procedure, moderate costs and off-the-shelf availability. Juvenile allograft cartilage contains 10x greater chondrocyte density than adult tissue and does not elicit an allogeneic immune response. PJAC is indicated both in small and large defects and has shown to provide hyaline-like cartilage. Short term patient reported outcomes are good to excellent. Disadvantages are the limited high-level evidence with no long-term data as well as the limited availability of donor tissue.

1. Adkisson, H. D., et al. The potential of human allogenic juvenile chondrocytes for restoration of articular cartilage. American Journal of Sports Medicine. 38(7):1324-33, 2010.
2. Adkisson, H. D., et al. Immune evasion by neocartilage-derived chondrocytes: Implications for biologic repair of joint 1. articular cartilage. Stem Cell Research. 4:57-68, 2010.
3. Federer, J., et al. The Promise of Chondral Repair Using Neocartilage. In Sandell, J. S., et al (red) Tissue Engineering in Musculoskeletal Clinical Practice. American Sample Copy Deck 2019 Academy of Orthopaedic Surgeons. Chapter 22, pp. 219-226, 2004.
4. Runer A, Salzmann GM (2022) Moving towards single stage cartilage repair—is there evidence for the minced cartilage procedure? Journal of Cartilage & Joint Preservation 2(2):

Contributor: Armin Runer

PEEK

Polyetheretherketone is a “high-performance” polymer that is biocompatible and belongs to polyaryletherketone (PAEK) family. PEEK has a comparable elastic modulus to cortical bone compared to metallic implants and therefore is widely used for orthopedic, trauma and spinal implants.

Contributor: Cemile Basgul

Piezoelectric materials

Piezoelectric materials, which can be both of organic and inorganic nature, can convert an applied mechanical force into an electric signal, and vice versa (reverse piezoelectric effect). The mechanisms that rule this phenomenon are different depending on the nature of the material. For organic materials, this process is related to the reorientation of the molecular dipoles inside the bulk polymer structure (polarization), which is promoted by either the stretching of the material or the application of an electrical field. This leads to the formation of a high net dipole moment that, in turn, induces an electrical stimulus. For inorganic materials, the piezoelectric phenomenon is associated with the displacement of ions inside the crystalline structure. This displacement occurs when the crystal is placed under mechanical stress, leading to changes in the atomic structure of the material and, therefore, shifts in the balance of ions in the structure and the creation of a dipole moment.

1. Chorsi, M. T., Curry, E. J., Chorsi, H. T., Das, R., Baroody, J., Purohit, P. K., Illies, H., & Nguyen, T. D. (2019). Piezoelectric biomaterials for sensors and actuators. Advanced Materials, 31(1), 1802084.

2. Khare, D., Basu, B., & Dubey, A. K. (2020). Electrical stimulation and piezoelectric biomaterials for bone tissue engineering applications. Biomaterials, 258, 120280.

3. Ribeiro, C., Sencadas, V., Correia, D. M., & Lanceros-Méndez, S. (2015). Piezoelectric polymers as biomaterials for tissue engineering applications. Colloids and Surfaces B: Biointerfaces, 136, 46-55.

4. Barbosa, F., Ferreira, F. C., & Silva, J. C. (2022). Piezoelectric electrospun fibrous scaffolds for bone, articular cartilage and osteochondral tissue engineering. International Journal of Molecular Sciences, 23(6), 2907.

Contributor: João C. Silva

Poroelasticity

A theoretical framework to describe the mechanical response (e.g. interstitial fluid pressure, friction, contact stiffness) of hydrated materials. The theory has been routinely applied to articular cartilage [1,2] and intervertebral disc [3]. At the most fundamental level, poroelasticity describes the interaction between a solid phase and fluid phase [4,5]. Increasing the number of constituents (e.g. fibers [6]) and their non-linear properties (hyper-elasticity [7]) have led to significant improvements in predicting the mechanical response of poroelastic materials.

Contributor: Axel Moore

Posterior root tears of the lateral meniscus

The lateral meniscus posterior root (LMPR) presents one attachment site of the meniscus to the tibial plateau and is part of the posterolateral suspensory complex which includes also the popliteomeniscal fascicles and the meniscofemoral ligaments [4, 9]. LMPR tears are highly associated with anterior cruciate ligament (ACL) injury. Their prevalence in ACL-injured patients is reported to be between 7% and 17% [7, 8]. According to Forkel et al. three different types of LMPR tears can be distinguished: (1) avulsion injury of the posterior LM root, (2) radial tear of the LM posterior horn close to the root, and (3) complete detachment with root tear and rupture of the meniscofemoral ligament [3]. In addition, referred to as type four lesion, Jacquet et al. described the elongation of the posterior root without arthroscopically visible interruption of meniscal tissue [5]. Since magnetic resonance imaging is not sensitive enough to detect LMPR tears, arthroscopy is the gold standard to diagnose these lesions [6]. In addition to the evaluation of the LMPR through the anterior portals, it is recommended to examine the posterolateral compartment also through a posterolateral portal [1]. Further, arthroscopic stability testing of the LMPR is recommended since instability and its biomechanical consequence is not determined by visible LMPR injury alone [5]. As LMPR tears were shown to significantly influence rotational knee laxity in ACL-injured patients, their repair is necessary to restore anatomical knee conditions [10, 11]. Depending on the type of injury, a transtibial refixation or an all-inside suture technique can be considered [2].

1.            Ahn JH, Oh I (2006) Arthroscopic all-inside lateral meniscus suture using posterolateral portal. Arthroscopy 22:572.e571-574

2.            Balke M, Metzlaff S, Faber S, Niethammer T, Roessler PP, Henkelmann R, et al. (2021) Posteriore Wurzelverletzungen der Menisken. Knie Journal 3:255-267

3.            Forkel P, Reuter S, Sprenker F, Achtnich A, Herbst E, Imhoff A, et al. (2015) Different patterns of lateral meniscus root tears in ACL injuries: application of a differentiated classification system. Knee Surg Sports Traumatol Arthrosc 23:112-118

4.            Frank JM, Moatshe G, Brady AW, Dornan GJ, Coggins A, Muckenhirn KJ, et al. (2017) Lateral Meniscus Posterior Root and Meniscofemoral Ligaments as Stabilizing Structures in the ACL-Deficient Knee: A Biomechanical Study. Orthop J Sports Med 5:2325967117695756

5.            Jacquet C, Mouton C, Magosch A, Komnos GA, Menetrey J, Ollivier M, et al. (2022) The aspiration test reveals an instability of the posterior horn of the lateral meniscus in almost one-third of ACL-injured patients. Knee Surg Sports Traumatol Arthrosc 30:2329-2335

6.            Krych AJ, Wu IT, Desai VS, Murthy NS, Collins MS, Saris DBF, et al. (2018) High Rate of Missed Lateral Meniscus Posterior Root Tears on Preoperative Magnetic Resonance Imaging. Orthop J Sports Med 6:2325967118765722

7.            Magosch A, Mouton C, Nührenbörger C, Seil R (2021) Medial meniscus ramp and lateral meniscus posterior root lesions are present in more than a third of primary and revision ACL reconstructions. Knee Surg Sports Traumatol Arthrosc 29:3059-3067

8.            Praz C, Vieira TD, Saithna A, Rosentiel N, Kandhari V, Nogueira H, et al. (2019) Risk Factors for Lateral Meniscus Posterior Root Tears in the Anterior Cruciate Ligament-Injured Knee: An Epidemiological Analysis of 3956 Patients From the SANTI Study Group. Am J Sports Med 47:598-605

9.            Shin HK, Lee HS, Lee YK, Bae KC, Cho CH, Lee KJ (2012) Popliteomeniscal fascicle tear: diagnosis and operative technique. Arthrosc Tech 1:e101-106

10.          Song GY, Zhang H, Liu X, Zhang J, Xue Z, Qian Y, et al. (2017) Complete posterolateral meniscal root tear is associated with high-grade pivot-shift phenomenon in noncontact anterior cruciate ligament injuries. Knee Surg Sports Traumatol Arthrosc 25:1030-1037

11.          Tang X, Marshall B, Wang JH, Zhu J, Li J, Smolinski P, et al. (2019) Lateral Meniscal Posterior Root Repair With Anterior Cruciate Ligament Reconstruction Better Restores Knee Stability. Am J Sports Med 47:59-65

Contributor: Amanda Magosch

Posterolateral Corner (PLC)

The posterolateral corner (PLC) is a collection of multiple structures on the lateral side of the knee consisting of primarily the lateral collateral ligament (LCL), popliteus tendon, and popliteofibular ligament (PLF). Secondary stabilizers include the arcuate ligament, lateral patellofemoral ligament, fabellofibular ligament, lateral head of the gastrocnemius, iliotibial band, and the long head of the biceps femoris. The PLC acts as a restraint to varus stress and external rotation of the tibia.

• Dean RS, LaPrade RF. ACL and Posterolateral Corner Injuries. Curr Rev Musculoskelet Med. 2020 Feb;13(1):123-132. doi: 10.1007/s12178-019-09581-3. PMID: 31884674; PMCID: PMC7083988.
  
• Maniar AR, White AE, Musahl V, Ranawat A. Posterolateral Corner of the Knee: An Update on Current Evaluation and Management Strategies. J Am Acad Orthop Surg. 2024 Jan 1;32(1):e13-e23. doi: 10.5435/JAAOS-D-23-00278. Epub 2023 Jul 19. PMID: 37476845.
• Ranawat A, Baker CL 3rd, Henry S, Harner CD. Posterolateral corner injury of the knee: evaluation and management. J Am Acad Orthop Surg. 2008 Sep;16(9):506-18. PMID: 18768708.
  
  

Contributor: Michael Gaudiani

Post-traumatic osteoarthritis (PTOA)

Osteoarthritis (OA) is one of the most common forms of joint abnormalities. Traumatic joint injuries that damage the articular cartilage surface result in the onset and progression of osteoarthritis, referred to as posttraumatic osteoarthritis (PTOA)1-3. Further, the trauma that results in intra-articular fracture, meniscal tearing, ligamentous and chondral injuries significantly increases the risk of establishment and progression of the disease 4-6. PTOA can occur in any joint and at any age, and the leading cause of PTOA includes any acute physical trauma, such as sports-related injuries, vehicle accidents, and exercise. PTOA also frequently occurs in military personnel due to intense physical activity and military combat. PTOA in the knee joint is more common than in the other joints. PTOA affects around 5 million individuals each year and constitutes 10-12% of all arthritis cases imposing significant clinical and financial burdens 7. Currently, there are no disease-modifying treatments for PTOA; however, various approaches, including the anti-inflammatory treatment, have provided promising avenues to combat the disease more efficiently 8,9.

1          Trivedi, J., Betensky, D., Desai, S. & Jayasuriya, C. T. Post-Traumatic Osteoarthritis Assessment in Emerging and Advanced Pre-Clinical Meniscus Repair Strategies: A Review. Front Bioeng Biotechnol 9, 787330 (2021). https://doi.org:10.3389/fbioe.2021.787330

2          Watt, F. E. Posttraumatic osteoarthritis: what have we learned to advance osteoarthritis? Curr Opin Rheumatol 33, 74-83 (2021). https://doi.org:10.1097/bor.0000000000000760

3          Little, C. B. & Hunter, D. J. Post-traumatic osteoarthritis: from mouse models to clinical trials. Nat Rev Rheumatol 9, 485-497 (2013). https://doi.org:10.1038/nrrheum.2013.72

4          Jiménez, G., Cobo-Molinos, J., Antich, C. & López-Ruiz, E. Osteoarthritis: Trauma vs Disease. Adv Exp Med Biol 1059, 63-83 (2018). https://doi.org:10.1007/978-3-319-76735-2_3

5          Borrelli, J., Jr. et al. Understanding Articular Cartilage Injury and Potential Treatments. J Orthop Trauma 33 Suppl 6, S6-s12 (2019). https://doi.org:10.1097/bot.0000000000001472

6          Favero, M., Ramonda, R., Goldring, M. B., Goldring, S. R. & Punzi, L. Early knee osteoarthritis. RMD Open 1, e000062 (2015). https://doi.org:10.1136/rmdopen-2015-000062

7          Punzi, L. et al. Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation. RMD Open 2, e000279 (2016). https://doi.org:10.1136/rmdopen-2016-000279

8          Hsia, A. W. et al. Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice. Osteoarthritis Cartilage 29, 1709-1719 (2021). https://doi.org:10.1016/j.joca.2021.09.014

9          Khella, C. M., Horvath, J. M., Asgarian, R., Rolauffs, B. & Hart, M. L. Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches. Int J Mol Sci 22 (2021). https://doi.org:10.3390/ijms22158005

Contributor: Jay Trivedi

Primary Bone Healing

Primary bone healing, also known as direct bone healing, occurs when the broken ends of the bone are closely aligned and rigidly fixed, allowing for the direct remodeling of bone without the formation of a callus. This process mimics normal bone remodeling and is typically achieved through surgical intervention, such as open reduction and internal fixation (ORIF). In primary bone healing, osteoclasts and osteoblasts work in tandem to create "cutting cones" that cross the fracture line. These cones facilitate the formation of new Haversian systems, leading to the restoration of the bone's original structure. This method is characterized by minimal interfragmentary motion and good vascularity at the site of the fracture, ensuring effective healing.

1.         Fracture Healing: Back to Basics and Latest Advances | SpringerLink. Accessed July 10, 2024. https://link.springer.com/chapter/10.1007/978-3-319-68628-8_1

2.         Willenegger H, Perren SM, Schenk R. [Primary and secondary healing of bone fractures]. Chir Z Alle Geb Oper Medizen. 1971;42(6):241-252.

3.         Kaderly RE. Primary bone healing. Semin Vet Med Surg (Small Anim). 1991;6(1):21-25.

Contributor: Nirav Mungalpara

Progenitor Cell

All normal adult tissue sources contain stem cells and progenitor cells that help in maintaining tissue homeostasis. While stem cells have the capacity to asymmetrically divide and self-renew, progenitor cells possess the capacity to divide symmetrically, often for many cell divisions to yield abundance of progeny. The progenitor cells ultimately differentiate into mature cells in the tissue.

Contributor: Venkata Mantripragada

Proteoglycan

Proteoglycans are complex high molecular weight biomolecules that are commonly found in the extraceullar matrix of soft tissues. They consist of a backbone core protein connected to glycosaminoglycan (GAG) side chains that form a structure to similar to a pipe brush. GAGs are highly negatively charged molecules and, as the pipe brush structure allows for a large reactive surface area, the GAG sidechains of a proteoglycan attract a significant amount of water into the tissue, defining the tissue's biomechanical and biochemical behavior.

Contributor: John Martin

Proteoglycan-4

Proteoglycan 4, also known as lubricin, is a protein that is encoded by the PRG4 gene in humans. It is primarily known for its role as a joint lubricant and is found in synovial fluid and on the surface of articular cartilage. Its presence is important for maintaining synovial homeostasis and for preventing friction and wear between moving joint surfaces. Initially, lubricin was identified as "superficial zone protein" (SZP) due to its location in the superficial layer of articular cartilage. It was later discovered that the 32-kDa amino terminal fragment of lubricin could stimulate the growth of megakaryocytes in vitro, leading to the protein being called "megakaryocyte-stimulating factor" (MSF). However, lubricin, MSF, and SZP are now collectively referred to as Proteoglycan 4 (PRG4). Although there is some debate over whether lubricin is actually a proteoglycan, it has been detected in various tissues throughout the body, including tendon, meniscus, lung, liver, heart, bone, ligament, muscle, and skin. It is even present in human plasma, where it binds to neutrophils via L-selectin. Overall, lubricin is an important protein for joint health and mobility, as well as for the normal functioning of various other tissues in the body.

Swann DA, Slayter HS, Silver FH. The molecular structure of lubricating glycoprotein-I, the boundary lubricant for articular cartilage. J Biol Chem. 1981 Jun 10;256(11):5921-5. PMID: 7240180.

Jay GD, Waller KA. The biology of lubricin: near frictionless joint motion. Matrix Biol. 2014 Oct;39:17-24. doi: 10.1016/j.matbio.2014.08.008. Epub 2014 Aug 27. PMID: 25172828.

Contributor: Austyn Matheson

PRP

Platelet-Rich Plasma: a blood-derived product exploiting the potential of platelet concentrates to provide a high concentration of growth factors and bioactive molecules for the promotion of tissue regeneration, repair, and homeostasis

Contributor: Giuseppe Filardo

Ramp lesions of the medial meniscus

Ramp lesions, also frequently referred to as “hidden lesions”, are lesions of the posterior horn of the medial meniscus located at the meniscocapsular or meniscosynovial junction. Most commonly, ramp lesions occur in association with anterior cruciate ligament (ACL) injuries. The pooled prevalence of ramp lesions is reported to be 22%, though varying from 9% to 42% depending on the study [5]. The diagnosis of ramp lesions with magnetic resonance imaging (MRI) or through the standard anterior arthroscopic portals is inadequate [2, 8]. Inspection of the posterior compartment through the anterolateral portal performing a trans-notch-view is possible. However, certain areas of the meniscal ramp are often still not visible. Therefore, additional palpation of the ramp with a needle through a posteromedial portal is recognized to be the gold standard to establish the diagnosis of a ramp lesion. Direct visualization of the ramp through the posteromedial portal is recommended if a ramp lesion is suspected or in any case of doubt [4, 8]. Various factors are described to be associated with the presence of a ramp lesion. Strong evidence is provided for a posteromedial tibial edema on MRI, age below 30 years, and complete ACL rupture, male sex and concomitant lateral meniscal tears provide moderate evidence, while the evidence for chronicity of ACL injury is low [5]. As ramp lesions were shown to significantly influence rotational knee laxity in ACL-injured patients, their repair is necessary to restore anatomical knee conditions [3, 6, 9]. Various techniques have been described to this end, including all-inside techniques and repair through a single or through two posteromedial portals [1, 7, 10].

1.            Acosta J, Ravaei S, Brown SM, Mulcahey MK (2020) Examining Techniques for Treatment of Medial Meniscal Ramp Lesions During Anterior Cruciate Ligament Reconstruction: A Systematic Review. Arthroscopy 36:2921-2933

2.            Greif DN, Baraga MG, Rizzo MG, Mohile NV, Silva FD, Fox T, et al. (2020) MRI appearance of the different meniscal ramp lesion types, with clinical and arthroscopic correlation. Skeletal Radiol 49:677-689

3.            Hatayama K, Terauchi M, Saito K, Takase R, Higuchi H (2020) Healing Status of Meniscal Ramp Lesion Affects Anterior Knee Stability After ACL Reconstruction. Orthop J Sports Med 8:2325967120917674

4.            Hoffmann A, Mouton C, Pape DD, Seil R (2017) VKB-assoziierte Rampenläsionen des medialen Meniskus. Arthroskopie 30:92-99

5.            Kunze KN, Wright-Chisem J, Polce EM, DePhillipo NN, LaPrade RF, Chahla J (2021) Risk Factors for Ramp Lesions of the Medial Meniscus: A Systematic Review and Meta-analysis. Am J Sports Med 49:3749-3757

6.            Mouton C, Magosch A, Pape D, Hoffmann A, Nührenbörger C, Seil R (2020) Ramp lesions of the medial meniscus are associated with a higher grade of dynamic rotatory laxity in ACL-injured patients in comparison to patients with an isolated injury. Knee Surg Sports Traumatol Arthrosc 28:1023-1028

7.            Siboni R, Pioger C, Jacquet C, Mouton C, Seil J, Toanen C, et al. (2022) Meniscal Ramp Repair: A 2-Portal Posteromedial Approach. Arthroscopy Techniques 11:e1163-e1169

8.            Sonnery-Cottet B, Conteduca J, Thaunat M, Gunepin FX, Seil R (2014) Hidden lesions of the posterior horn of the medial meniscus: a systematic arthroscopic exploration of the concealed portion of the knee. Am J Sports Med 42:921-926

9.            Stephen JM, Halewood C, Kittl C, Bollen SR, Williams A, Amis AA (2016) Posteromedial Meniscocapsular Lesions Increase Tibiofemoral Joint Laxity With Anterior Cruciate Ligament Deficiency, and Their Repair Reduces Laxity. Am J Sports Med 44:400-408

10.          Thaunat M, Fayard JM, Guimaraes TM, Jan N, Murphy CG, Sonnery-Cottet B (2016) Classification and Surgical Repair of Ramp Lesions of the Medial Meniscus. Arthroscopy Techniques 5:e871-e875

Contributor: Amanda Magosch

Rapidly destructive osteoarthritis

Rapidly destructive osteoarthritis (RDOA, a.k.a. rapidly progressive osteoarthritis, RPOA) is a rare clinical entity that has so far been described only for the hip and shoulder joints. RDOA presents with a quick onset and evolution that is clearly shown in radiographic imaging, which is the only diagnostic tool of this disease, along with the exclusion of other causes of rapidly evolving joint disease such as sepsis, rheumatoid arthritis, crystalline arthropathy or osteonecrosis.

Baroncini, A., et al. (2022). Rapidly destructive osteoarthritis of the spine: Lessons learned from the first reported case.
https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-022-05686-y

Contributor: Tim Ludwig Tuengler

Reamer-Irrigator-Aspirator (RIA) System

The Reamer-Irrigator-Aspirator (RIA) System, is a surgical drill device that enables intramedullary reaming of long bones with a significant reduction of intraosseus pressure and donor site morbidity. The RIA head simultaneously flushes the reaming canal with physiological saline and harvests bone marrow along with morselized bone chips for autograft transplantation. This technique is especially used when high volumes of autologous bone graft, e.g. in large bone and non-union defects, are needed. The device generates a solid transplant and a "wash through" phase that also contains a plethora of viable cells and growth factors.

Contributor: Sebastian Haeusner

Regeneration

The renewal of a tissue or organ at the completion of healing.

Contributor: Myron Spector

Regenerative Medicine

A multidisciplinary approach which utilises aspects of cell biology, material science and engineering in order to regenerate tissues through a combination of cells, biomaterial scaffolds, and signalling factors.

Contributor: Eamon Sheehy

Regulatory T-Cells (Tregs)

Tregs are a specialized type of CD4+ T-cell that express the transcription factor Foxp3, with a wide range of functions. Broadly, Tregs are involved in immune tolerance and are known for their role in suppressing over active immune responses. More recently, Tregs have been identified as cells with important roles in tissue regeneration by secreting cytokines that promote activation and proliferation of resident stem cell and progenitor cells and by modulating the local immune environment to a pro-regenerative immune landscape.

Contributor: Varun Arvind

Remodeling/ Maintenance/ Turnover

The process by which extracellular matrix is replaced in a process of degradation followed by synthesis.

Contributor: Myron Spector

Repair

The formation of scar at a site of injury at the completion of healing. In musculoskeletal tissue, scar comprises fibrous tissue, and in neural tissue, "scar" refers to a neuroma.

Contributor: Myron Spector

Rotator Cuff Injury

Rotator cuff injury (RCI) is associated with trauma and aging. Acute high-impact trauma including anterior dislocation of the shoulder and humerus head fracture damages connective tissue surrounding the shoulder. Internal subacromial impingement may arise from the curved and hooked acromion. Chronic subacromial impingement accelerates the supraspinatus degeneration and rotator cuff tear. On the other hand, with the lack of mechanical loading stimulation, supraspinatus tendon cells start to go through apoptosis and lose the orientation of collagen fiber.

1. Fu, C., Huang, A. H., Galatz, L. M. and Han, W. M. (2021). Cellular and molecular modulation of rotator cuff muscle pathophysiology. J Orthop Res. 39, 2310-2322.

2. Fang, F., Schwartz, A. G., Moore, E. R., Sup, M. E. and Thomopoulos, S. (2020). Primary cilia as the nexus of biophysical and hedgehog signaling at the tendon enthesis. Sci Adv. 6 (44):eabc1799.

3. Lawrence, R. L., Moutzouros, V. and Bey, M. J. (2019). Asymptomatic Rotator Cuff Tears. JBJS Rev. 7, e9. 

Contributor: Meng Feng

Scaffold

Biomaterial that act as template for tissue regeneration, to guide the growth of new tissue. Main features are: 1) allow cell attachment and migration; 2) deliver and retain cells and biochemical factors; 3) enable diffusion of vital cell nutrients and expressed products; 4) exert certain mechanical and biological influences to modify cells behavior

Contributor: Fabrizio Russo

Scleraxis

A protein member of bHLH transcript factors, marker for tendon and ligament progenitors and is continuously expressed trough differentiation into the mature tendons.

Contributor: Mariya Hadzhinikolova

Secretome

Secretome: cell-secreted proteins (e.g., growth factors, cytokines, chemokines enzymes, shed receptors, extracellular matrix constituents) that regulate numerous biological processes through autocrine and paracrine signaling mechanisms. In particular, the secretome from mesenchymal stem cells (MSCs) has emerged as a promising candidate for an acellular therapeutic to augment tissue repair and regeneration.

Contributor: Jason C. Marvin

Self-Assembly

Tissue engineering process in which biomimetic and functional tissue can be created without the influence of external energy or force. The self-assembling process is scaffoldless and mimics developmental biology by using a nonadherent substrate to support high-density cell seeding, thereby minimizing tissue free energy and facilitating cell-cell adherence and interaction. Self-assembly can be used to generate functional cartilaginous tissue (e.g., hyaline articular cartilage, meniscal fibrocartilage, fibrocartilage of the temporomandibular joint) with characteristics similar to native tissue.

1. Lee JK, Link JM, Hu JC, Athanasiou KA.The Self-Assembling Process and Applications in Tissue Engineering. Cold Spring Harb Perspect Med. 2017 Nov 1;7(11):a025668.

2. Hu JC, Athanasiou KA. A self-assembling process in articular cartilage tissue engineering. Tissue Eng. 2016 Apr;12(4):969-79.

Contributor: Dean Wang

Semitendinosus

A uniquely structured posterior thigh muscle split into two separate neuromuscular compartments by a tendinous inscription. Its main actions are to flex the knee and extend the hip, but it also plays a role in tibial internal rotation and reducing load imposed on the anterior cruciate ligament. Functionally, the semitendinosus muscle is generally hypertrophied in sprinters. Clinically, (i) the muscle is often affected in cerebral palsy, and (ii) the distal tendon is often harvested for anterior cruciate ligament reconstruction.

1. Haberfehlner, H., Maas, H., Harlaar, J., Becher, J.G., Buizer, A.I. & Jaspers, R.T. (2016). Freehand three-dimensional ultrasound to assess semitendinosus muscle morphology. Journal of Anatomy, 229(4):591–599. https://doi.org/10.1111/joa.12501 

2. Handsfield, G.G., Knaus, K.R., Fiorentino, N.M., Meyer, C.H., Hart, J.M. & Blemker, S.S. (2017). Adding muscle where you need it: non-uniform hypertrophy patterns in elite sprinters. Scandinavian Journal of Medicine & Science in Sports, 27(10):1050– 1060. https://doi.org/10.1111/sms.12723 

3. Kositsky, A., Saxby, D.J., Lesch, K.J., Barrett, R.S., Kröger, H., Lahtinen, O. et al. (2022). In vivo assessment of the passive stretching response of the bicompartmental human semitendinosus muscle using shear-wave elastography. Journal of Applied Physiology, 132(2):438–447. https://doi.org/10.1152/japplphysiol.00473.2021 

4. Kositsky, A., Maas, H., Barrett, R.S., Kennedy, B., Stenroth, L., Korhonen, R.K., Vertullo, C.J., Diamond, L.E., Saxby, D.J. (2023). Morphology of proximal and distal human semitendinosus compartments and the effects of distal tendon harvesting for anterior cruciate ligament reconstruction. Journal of Anatomy, 243(2):297-310. https://doi.org/10.1111/joa.13869 

Contributor: Adam Kositsky

Senescence

A state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype—SASP). It can be induced in primary cells in response to a variety of noxious stimuli such as DNA damage, oxidative stress, and oncogene expression, among others. Senescence was first described by Hayflick in 1961. Senescence in general persists even after removal of the inducing stimulus, albeit senescent cancer cells may be the exception to this rule. It can be distinguished from quiescence. Senescence is a tumor-suppressive barrier to cancer formation. Studies have reported that the re-expression of p53 within p53-deficient solid tumors leads to reactivation of senescence in tumor cells. However, prolonged aberrant persistence of senescent cells can have detrimental effects in promoting cancer. Senescent cells have functional roles in embryonic development, regeneration and reprogramming. The controlled induction of senescence appears to be beneficial in many conditions including tumor suppression, development, reprogramming and regeneration.

Contributor: Rafael Llombart

Senotherapy

An umbrella term that encompasses therapies targeting cellular senescence and/or the cognate Senescence Associated Secretory Phenotype (SASP). These typically include two classes of pharmacologics: Senolytics, which selectively eliminate senescent cells, and senomorphics which reduce the pro-inflammatory and anti-regenerative SASP factors released by senescent cells.

Niedernhofer LJ & Robbins PD. Senotherapeutics for healthy aging. Nature Reviews: Drug Discovery. 2018. doi.org/10.1038/nrd.2018.44

Raffaele M & Vinciguerra M. The costs and benefits of senotherapeutics for human health. Lancet: Healthy Longevity. 2022. doi.org/10.1016/S2666-7568(21)00300-7

Contributor: sealy hambright

Skeletal Innervation

Bone is innervated by both the sensory and autonomic nervous system. In both long bones and the calvaria, the periosteum is densely innervated, while the bone marrow exhibits fewer nerves. Cortical bone itself is not innervated, however, nerves travel along with blood vessels through transcortical canals to reach the marrow space. Skeletal nerves exist as free nerve endings and secrete neuropeptides and respond to changes in the bone microenvironment.

1.     Hassan MG, Horenberg AL, et al. Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications. Current Osteoporosis Reports. 2023; 21, 503–518

Contributor: Allison Horenberg

SLAP

A SLAP lesion (Superior Labrum from Anterior to Posterior tear) generally occurs as result of overuse injury to the shoulder in overhead athletes or traumatic falls in older patients and can result in deep shoulder pain and biceps tendonitis. They can be classified in: Type I: Labral and biceps fraying, anchor intact. Type II: Labral fraying with detached biceps tendon anchor Type III: Bucket handle tear, intact biceps tendon anchor Type IV: Bucket handle tear with detached biceps tendon anchor Type V: Type II + anteroinferior labral extension Type VI: Type II + unstable flap Type VII: Type II + MGHL injury Type VIII: Type II + posterior extension Typer IX: Circumferential Type X: Type II + posteroinferior extension

Contributor: Marcos González Alonso

Spontaneous osteonecrosis of the knee (SONK)

Spontaneous osteonecrosis of the knee (SONK) is a phenomenon of localized vascular insufficiency that results in subchondral necrosis and disruption of nutrient flow to overlying cartilage typically found in middle-aged women at the articular portion of the medial femoral condyle. Debate still exists regarding the exact etiology, the influence of meniscal insufficiency, and correct management algorithms.

1) Sibilska, Aleksandra, et al. "Spontaneous osteonecrosis of the knee: what do we know so far? A literature review." International Orthopaedics 44 (2020): 1063-1069.

2) Breer, S., et al. "Spontaneous osteonecrosis of the knee (SONK)." Knee Surgery, Sports Traumatology, Arthroscopy 21 (2013): 340-345.

Contributor: Joe Kocan

Stem Cells

Undifferentiated cells that retain the ability to divide throughout life and give rise to cells that can become highly specialized and take the place of cells that die or are lost. Stem cells contribute to the body's ability to renew and repair its tissues.

Contributor: Travis Frantz

Subchondral Bone

One component of the osteochondral unit found in joints including the ankle, knee, shoulder and hip. While there is inconsistency in defining where the subchondral bone starts, as defined by Madry et al. it begins immediately after and deep to the calcified cartilage as separated by the cement line. Functions of the subchondral bone include maintaining the joint shape, resisting stress, shock absorption and delivering nutrients through its vascular network.

 -  Madry, H.; van Dijk, C.N.; Mueller-Gerbl, M. The basic science of the subchondral bone. Knee Surg. Sports Traumatol. Arthrosc. 2010, 18, 419–433. 

-  Kawcak, C.E.; McIlwraith, C.W.; Norrdin, R.W.; Park, R.D.; James, S.P. The role of subchondral bone in joint disease: A review. Equine Vet. J. 2001, 33, 120–126.

Contributor: Stephanie Doyle

synovial fluid

Synovial fluid is the viscous, non-Newtonian fluid within the cavity of synovial joints. It is made from blood plasma ultrafiltrate and contains several putative lubricating molecules, including hyaluronic acid (HA), lubricin/PRG4, and surface active phospholipids. Synovial fluid's primary functions are to lubricate the cartilage surface and exchange nutrients and waste products with cartilage via diffusion.

Contributor: Meghan Kupratis

TBJ

The tendon-bone junction (TBJ), also called enthesis, is a functionally graded tissue material that provides the transition from a soft tissue tendon to hard mineralized bone. It consists of four layers: tendon, fibrocartilage, mineralized fibrocartilage and bone. The native TBJ plays a crucial role in transferring mechanical forces between muscles and bones and in maintaining joint stability.

Contributor: Wouter Van Genechten

Tendon

Fibrous connective tissue that connects muscle to bone. Tendons primarily function by transmitting the contraction force produced by muscle to bone, thereby enabling movement. Tendons are composed of 55–70% water, and the extracellular matrix is primarily composed of aligned type I collagen fibers.

Contributor: Natalie Leong

Tenocytes

Tenocytes are fibroblastic cells formed from tenoblasts. They are responsible for the synthesis and turnover of their extracellular matrix comprising type I collagen tendon fibres and and noncollagenous proteins. Furthemore, tenocytes react to external mechanical as well as chemical stimuli and subsequently facilitate the functional adaptation of the tendon to its mechanical requirements.

Kannus P. Structure of the tendon connective tissue. Scandinavian Journal of Medicine and Science in Sports. 2000; 10: 312-320.

Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling. Journal of Musculoskeletal Neuronal Interact. 2006; 6 (2): 181-190.

Contributor: Eoghan Hurley

Tenomoduline

A type II transmembrane glycoprotein, encoded by TNMD gene, predominantly expressed in tendons and ligaments.

Contributor: Mariya Hadzhinikolova

Theranostic

Theranostic - a single treatment system that can simultaneously improve and aid in monitoring areas of the body exhibiting signs of disease. The combination of therapeutic and diagnostic.

Contributor: Anisha Joenathan

Tibial slope

The tibial slope, known as posterior or proximal tibial slope (PTS), represents the inclination of the tibial plateau and is determined by the angle formed between the vertical line of the tibial anatomical axis and the tangent of the tibial plateau. It plays a crucial role in maintaining knee joint stability and influencing biomechanics. Research has shown a correlation between a higher tibial slope and an increased risk of anterior cruciate ligament (ACL) injuries or failure following ACL reconstruction. Recent expert opinions recommend addressing the elevated tibial slope as part of the revision procedure in revision ACL surgeries.

1. Winkler PW, Godshaw BM, Karlsson J, Getgood AMJ, Musahl V. Posterior tibial slope: the fingerprint of the tibial bone. Knee Surg Sports Traumatol Arthrosc. 2021;29(6):1687-1689. doi:10.1007/s00167-021-06578-9

2. Vivacqua T, Thomassen S, Winkler PW, et al. Closing-Wedge Posterior Tibial Slope-Reducing Osteotomy in Complex Revision ACL Reconstruction. Orthop J Sports Med. 2023;11(1):23259671221144786. Published 2023 Jan 11. doi:10.1177/23259671221144786

Contributor: M. Enes Kayaalp

Tibialis Anterior

The tibialis anterior is a muscle situated in the anterior-lateral side of the tibia. The origin is the upper two parts of the lateral side of the tibia, the interosseus membrane and the deep surface of the fascia cruris. Its long tendon inserts at the medial and plantar cuneiform bone, and the base of metatarsal bone one. The tibialis anterior muscle is responsible for dorsiflexion and inversion of the foot and therefore important for the first phase of the gait.

Contributor: Kristina Hüsers

Tibiofibular syndesmosis

Composed of multiple ligaments and a broad interosseous membrane spanning the entire length of the tibia and fibula, the tibiofibular syndesmosis plays a vital role in ankle stability (1). Its distal osseous portion is made up of four components: the anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), transverse tibiofibular ligament, and the interosseous membrane.

Hermans JJ, Beumer A, de Jong TA et-al. Anatomy of the distal tibiofibular syndesmosis in adults: a pictorial essay with a multimodality approach. J. Anat. 2011;217 (6): 633-45.

Contributor: Bedri Karaismailoglu

Tissue

An aggregation of similarly specialized cells united in the performance of a particular function. Cells serving the same general function and having the same extracellular matrix.

Contributor: Myron Spector

Tissue Engineering

Tissue Engineering (TE) is a multidisciplinary approach which utilises aspects of cell biology, material science and engineering in order to regenerate tissues through a combination of cells, biomaterial scaffolds, and signalling factors.

Contributor: Eamon Sheehy

Transcriptomics

Molecular biology discipline that uses RNA-sequencing to characterize the gene expression profiles of tissues by quantifying protein-coding RNA. This can include whole tissue or single-cell methods and allows for the unbiased study of the underlying biology of musculoskeletal tissues. Additionally, this methodology is useful to understand and compare gene expression profiles of tissues in different anatomical regions (ex. upper vs. lower extremity) or phenotypic states (ex. healthy vs. injured), ultimately helping provide the foundation for targeted orthoregenerational therapies.

Ayturk U. RNA-seq in Skeletal Biology. Curr Osteoporos Rep. 2019 Aug;17(4):178-185. doi: 10.1007/s11914-019-00517-x. PMID: 31093870.

Sarmiento P, Little D. Tendon and multiomics: advantages, advances, and opportunities. NPJ Regen Med. 2021 Oct 1;6(1):61. doi: 10.1038/s41536-021-00168-6. PMID: 34599188.

Thomas SM, Ackert-Bicknell CL, Zuscik MJ, Payne KA. Understanding the Transcriptomic Landscape to Drive New Innovations in Musculoskeletal Regenerative Medicine. Curr Osteoporos Rep. 2022 Apr;20(2):141-152. doi: 10.1007/s11914-022-00726-x. Epub 2022 Feb 14. PMID: 35156183.

Contributor: Nathaniel Disser

Trans-Iliac Antibiotic-Labelled Bone Biopsy

One important step in diagnosing metabolic bone disease (MBD) is differentiating between calcified and uncalcified bone matrix. Tetracycline double labelled bone biopsy dates back at least to 1969 [1,2] and takes advantage of the property of this class of antibiotics to be deposited along the front of active calcification in bone and therefore allows visualization of active bone formation under fluorescent microscopy. Patients are given tetracycline or declomycin prior to bone biopsy to allow for dynamic analysis of osteoblastic/osteoclastic activity and mineralization processes, which can help distinguish low turnover from high turnover disease [3-5]. Bone biopsy allows for evaluation of histomorphometric patterns, which vary significantly between MBD’s and can therefore assist in diagnosis. Bone biopsy is indicated to further clarify cases of unexplained fragility fractures or to evaluate the effects of different treatments on bone [6-8], such as antiresorptive or anabolic drugs and their potential side effects [9]. The study of localization, levels of expression, and synthesis of important targets in bone and its microenvironment is now possible through application of in situ hybridization histochemistry (ISHH) and/or immunohistochemistry (IHC). ISHH allows study of specific mRNA expression and IHC determines the presence and distribution of target protein in cells. Combining the established bone histomorphometric techniques with ISHH and IHC has the ability to elevate the diagnostic and therapeutic utility of this procedure [10].

1.       Frost HM, Vilanueva AR, Jett S, Eyring E (1969) Tetracycline-based analysis of bone remodelling in osteopetrosis. Clinical orthopaedics and related research 65:203-217

2.       Frost HM (1969) Tetracycline-based histological analysis of bone remodeling. Calcif Tissue Res 3:211-237

3.       Wu K, Frost HM (1969) Bone formation in osteoporosis. Appositional rate measured by tetracycline labeling. Arch Pathol 88:508-510

4.       Dalle Carbonare L, Valenti MT, Giannini S, Gallieni M, Stefani F, Ciresa R, Politi C, Fusaro M (2021) Bone Biopsy for Histomorphometry in Chronic Kidney Disease (CKD): State-of-the-Art and New Perspectives. J Clin Med 10:

5.       Dalle Carbonare L, Giannini S (2004) [Histologic diagnosis of metabolic bone diseases: bone histomorphometry]. Reumatismo 56:15-23

6.       Dempster DW, Cosman F, Kurland ES, et al. (2001) Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16:1846-1853

7.       Dempster DW, Roschger P, Misof BM, Zhou H, Paschalis EP, Alam J, Ruff VA, Klaushofer K, Taylor KA (2016) Differential Effects of Teriparatide and Zoledronic Acid on Bone Mineralization Density Distribution at 6 and 24 Months in the SHOTZ Study. J Bone Miner Res 31:1527-1535

8.       Dempster DW, Zhou H, Recker RR, et al. (2016) Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study. J Clin Endocrinol Metab 101:1353-1363

9.       Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294-1301

10.       Langub MC, Faugere MC, Malluche HH (2000) Molecular bone morphometry. Pediatr Nephrol 14:629-635

Contributor: Juan Manuel Colazo

Translational Research

Applying methodology and knowledge of scientific research in the area of basic science and/or clinical science, to address current needs and answer important or novel questions in clinical medicine, with the ultimate to improve the health of all.

Contributor: Alvin Weii Su

Type 1 Fibrocartilage

Mesenchymal stem cells repair articular cartilage defects following bone marrow venting principally with fibrocartilage comprising chondrocytes in lacunae within an extracellular matrix made up of type I collagen in a fibrous structure (1). Type 1 fibrocartilage is characterized by bundles of thick clearly defined type-I collagen fibers, with unicellular islands of hyaline cartilage arranged in small chains (2). Fibrocartilage has moderate proteoglycans but low content of glycosaminoglycans. As we age the amount of fibrocartilage increases as hyaline cartilage transforms into fibrocartilage (3). Fibrocartilage is suited to meet the functional/mechanical demands of meniscus and labrum, but is biomechanically inferior to hyaline cartilage for the articularing surface of joints.

Contributor: Hayden Baker

VAS

Visual Analogue Scale is a 10-point likert scale used to measure a patient's perceived pain. It may be recorded pre- and post-operatively as a measurement of treatment success. It is an important tool for the assessment of regenerative therapies. A change of 2.5 points is considered to be the minimum clinically important difference (MCID).

Contributor: Eoghan Hurley

Velpeau

Velpeau is a special shoulder radiograph method which is an alternative to the axial shoulder X-Ray if an adequate abduction of the shoulder is not possible. In an acute trauma situation or in case of advanced arthrotic deformations, this might often be the case. For the velpeau radiograph the arm is in adduction to the body. The upper body is reclined for about 30° and the X-Ray is taken from above. The velpeau X-Ray allows a good view to the joint space, an evaluation of glenohumeral distances and uncertain dislocations.

https://www.dvse.info/downloads/bildgebung.html

Contributor: Johanna Habarta

Viscosupplementation

Exogenous intraarticular administration of hyaluronic acid for the treatment of symptomatic osteoarthritis. Viscosupplementation has the goal to increase joint lubrication as well as to exert antiinflammatory and analgesic effects.

Contributor: Luca Ambrosio

Voxel-based Morphometry

Voxel-based morphometry is an automated whole-brain analysis technique used to investigate regional and subregional microstructural changes in the brain. It allows researchers to compare brain images from different individuals or groups, such as those born prematurely, to identify differences in gray matter volume, white matter integrity, and other structural features. By analyzing voxel-wise differences, VBM provides insights into brain development, aging, and various neurological conditions

 Ortibus, E. L., De Cock, P. P., & Lagae, L. G. (2011). Visual perception in preterm children: what are we currently measuring? Pediatric Neurology, 45(1), 1-10. doi: 10.1016/j.pediatrneurol.2011.02.008

Contributor: belma nalbant

Wharton’s Jelly

Connective tissue found in the umbilical cord that is rich in mesenchymal stem cells. Advantages of Wharton’s jelly derived stem cells include minimally invasive harvest, high cell yield, differentiation potential, and low immunogenicity.

Contributor: Josiah Valk

WOMAC

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is one of the most utilized clinical scores to assess the impact of knee and hip osteoarthritis. It consists of a self-administered questionnaire with 24 items subdivided into 3 sub scales: pain (5 items: during walking, using stairs, in bed, sitting or lying, and standing upright), stiffness (2 items: after first waking and later in the day) and function (17 items: using stairs, rising from sitting, standing, bending, walking, getting in/out of a car, shopping, putting on/taking off socks, rising from bed, lying in bed, getting in/out of bath, sitting, getting on/off toilet, heavy domestic duties, light domestic duties). Each item is graded on a scale of 0-4, corresponding to: none (0), mild (1), moderate (2), severe (3), and extreme (4). Higher scores indicate an increased burden of disease.

Contributor: Luca Ambrosio