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

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

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 Marin

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 Alm

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

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

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

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 Marin

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

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

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

Development

The process of growth and differentiation of tissues and organs.

Contributor: Myron Spector

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

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

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

Growth Factor

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

Contributor: Fabrizio Russo

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 Marin

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

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

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

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
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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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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