Glossary

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


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.

1. Ames CP, et al. Cervical radiographical alignment: comprehensive assessment techniques and potential importance in cervical myelopathy. Spine. 2013. 
2. Benoist, M. Natural history of the aging spine. Eur Spine J. 2003.
3. Chen Y, et al. The change of cervical spine alignment along with aging in asymptomatic population: a preliminary analysis. Eur Spine J. 2017.
4. Määttä JH, etal. Phenotype profiling of Modic changes of the lumbar spine and its association with other MRI phenotypes: a large-scale population-based study. Spine J. 2015.
5. Le Huec JC, et al. Sagittal balance of the spine. Eur Spine J. 2019.
Iyer S, etal. Impact of cervical sagittal alignment parameters on neck disability. Spine. 2016.
6. Szpalski M, etal. The aging of the population: a growing concern for spine care in the twenty-first century. Eur Spine J. 2003.
7. Yeh KT, etal. Are there age- and sex-related differences in spinal sagittal alignment and balance among Taiwanese asymptomatic adults? Clin Orthop Relat Res. 2018.

Contributor: Youping Tao


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.

1] Strong DM. Tissue banking, biovigilance and the notify library. Cell Tissue Bank. 2018 Jun;19(2):187-195. doi: 10.1007/s10561-017-9639-0. Epub 2017 Jun 30. PMID: 28667461.
[2] Nikolaou VS, Giannoudis PV. History of osteochondral allograft transplantation. Injury. 2017 Jul;48(7):1283-1286. doi: 10.1016/j.injury.2017.05.005. Epub 2017 May 11. PMID: 28551056.

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.

1. Gobbi A, Espregueira-Mendes J, Lane J, Karahan M (eds). Bio-orthopaedics: a new approach. Berlin: Springer-Verlag, 2017.
2. Duarte Lana JFS, Andrade Santana MH, Dias Belangero W, Malheiros Luzo AC. Platelet-Rich Plasma: Regenerative Medicine: Sports Medicine, Orthopedic, and Recovery of Musculoskeletal Injuries. Berlin: Springer-Verlag, 2014.
3. Ross MH, Wojciech P (eds). Histology: a text and atlas: with correlated cell and molecular biology. 6th edn. Baltimore: Lippincott Williams and Wilkins, 2011.

Contributor: Theodorakys Marin


Atrophy

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

Contributor: Myron Spector


Augment (biologic)

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.

Smith B, Goldstein T, Ekstein C. Biologic adjuvants and bone: current use in orthopedic surgery. Curr Rev Musculoskelet Med. 2015;8(2):193-199. doi:10.1007/s12178-015-9265-z

Contributor: Richard Danilkowicz


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.

Sochacki KR, Varshneya K, Calcei JG, Safran MR, Abrams GD, Donahue J, Chu C, Sherman SL. Comparison of Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation of the Knee in a Large Insurance Database: Reoperation Rate, Complications, and Cost Analysis. Cartilage. 2020 Oct 27:1947603520967065. doi: 10.1177/1947603520967065. Epub ahead of print. PMID: 33106002.

Contributor: Georgios Chalatsis


Avascular Bone Necrosis

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

1. Bachiller FG, Caballer AP, Portal LF. Avascular necrosis of the femoral head after femoral neck fracture. Clin Orthop Relat Res. 2002 Jun. 87-109
2. Steffen RT, Athanasou NA, Gill HS, Murray DW. Avascular necrosis associated with fracture of the femoral neck after hip resurfacing: histological assessment of femoral bone from retrieval specimens. J Bone Joint Surg Br. 2010 Jun. 92(6):787-93.
3. Weinstein, S. L., & Buckwalter, J. A. (2005). Turek's orthopaedics: Principles and their application., p. 357  Philadelphia: Lippincott Williams & Wilkins.

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


Biologic

Products of living organisms, and the organisms themselves.

Contributor: Myron Spector


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


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.

[1] A.C. Moore, D.L. Burris, An analytical model to predict interstitial lubrication of cartilage in migrating contact areas, J. Biomech. 47 (2014) 148–153. doi:10.1016/j.jbiomech.2013.09.020.
[2] J. Charnley, The Lubrication of Animal Joints in Relation to Surgical Reconstruction by Arthroplasty, Ann. Rheum. Dis. 19 (1960) 10–19. doi:10.1136/Ard.19.1.10.
[3] E.D. Bonnevie, D. Galesso, C. Secchieri, I. Cohen, L.J. Bonassar, Elastoviscous transitions of articular cartilage reveal a mechanism of synergy between lubricin and hyaluronic acid, PLoS One. 10 (2015) 1–15. doi:10.1371/journal.pone.0143415.
[4] G.D. Jay, J.R. Torres, D.K. Rhee, H.J. Helminen, M.M. Hytinnen, C.J. Cha, K. Elsaid, K.S. Kim, Y. Cui, M.L. Warman, Association between friction and wear in diarthrodial joints lacking lubricin, Arthritis Rheum. (2007). doi:10.1002/art.22974.
[5] A.C. Moore, D.L. Burris, Tribological rehydration of cartilage and its potential role in preserving joint health, Osteoarthr. Cartil. 25 (2016) 99–107. doi:10.1016/j.joca.2016.09.018.
[6] J.P. Gleghorn, L.J. Bonassar, Lubrication mode analysis of articular cartilage using Stribeck surfaces, J. Biomech. 41 (2008) 1910–1918. doi:10.1016/j.jbiomech.2008.03.043.
[7] D. Dowson, V. Wright, M.D. Longfield, Human joint lubrication, Biomed. Eng. (NY). 4 (1969) 160–165.
[8] S.A. Maas, B.J. Ellis, G.A. Ateshian, J.A. Weiss, FEBio: Finite Elements for Biomechanics, J. Biomech. Eng. Asme. 134 (2012). doi:10.1115/1.4005694.
[9] M.A. Accardi, D. Dini, P.M. Cann, Experimental and numerical investigation of the behaviour of articular cartilage under shear loading-Interstitial fluid pressurisation and lubrication mechanisms, Tribol. Int. 44 (2011) 565–578. doi:10.1016/j.triboint.2010.09.009.
[10] D.H. Cortes, J.T. Nathan, J.F. DeLucca, E.M. Dawn, Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering, J. Biomech. 47 (n.d.) 2088–2094.
[11] V.C. Mow, S.C. Kuei, W.M. Lai, C.G. Armstrong, Biphasic Creep and Stress-Relaxation of Articular-Cartilage in Compression - Theory and Experiments, J. Biomech. Eng. Asme. 102 (1980) 73–84.
[12] C.W. McCutchen, The frictional properties of animal joints, Wear. 5 (1962) 1–17. doi:10.1016/0043-1648(62)90176-X.
[13] G.A. Ateshian, V. Rajan, N.O. Chahine, C.C. Guterl, C.T. Hung, Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena, J. Biomech. Eng. 131 (2009) 061003. doi:10.1115/1.3118773.
[14] A.C. Moore, J.F. DeLucca, D.M. Elliott, D.L. Burris, Quantifying Cartilage Contact Modulus, Tension Modulus, and Permeability With Hertzian Biphasic Creep., J. Tribol. 138 (2016) 414051–414057. doi:10.1115/1.4032917.
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. 
Link to Contributor: http://www.axelcmoore.com/
[1] A.C. Moore, D.L. Burris, An analytical model to predict interstitial lubrication of cartilage in migrating contact areas, J. Biomech. 47 (2014) 148–153. doi:10.1016/j.jbiomech.2013.09.020.
[2] J. Charnley, The Lubrication of Animal Joints in Relation to Surgical Reconstruction by Arthroplasty, Ann. Rheum. Dis. 19 (1960) 10–19. doi:10.1136/Ard.19.1.10.
[3] E.D. Bonnevie, D. Galesso, C. Secchieri, I. Cohen, L.J. Bonassar, Elastoviscous transitions of articular cartilage reveal a mechanism of synergy between lubricin and hyaluronic acid, PLoS One. 10 (2015) 1–15. doi:10.1371/journal.pone.0143415.

Contributor: Axel Moore


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.

1. Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full- thickness knee cartilage lesions. Cartilage 2011;2:286-299. 

Contributor: LEONARDO CAVINATTO


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.

1. Utsunomiya H, Gao X, Deng Z, et al. Improvement of Cartilage Repair With Biologically Regulated Marrow Stimulation by Blocking TGF-β1 in A Rabbit Osteochondral Defect Model. Orthop J Sports Med. 2019;7(7 suppl5):2325967119S00263. Published 2019 Jul 29. doi:10.1177/2325967119S00263

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).

1. Hubbard MJ. Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study. J Bone Joint Surg Br. 1996;78(2):217-219.
2. Gowd AK, Cvetanovich GL, Liu JN, et al. Management of Chondral Lesions of the Knee: Analysis of Trends and Short-Term Complications Using the National Surgical Quality Improvement Program Database. Arthroscopy. 2019;35(1):138-146.
3. McCormick F, Harris JD, Abrams GD, et al. Trends in the surgical treatment of articular cartilage lesions in the United States: an analysis of a large private-payer database over a period of 8 years. Arthroscopy. 2014;30(2):222-226.
4. Kang RW, Gomoll AH, Nho SJ, Pylawka TK, Cole BJ. Outcomes of mechanical debridement and radiofrequency ablation in the treatment of chondral defects: a prospective randomized study. J Knee Surg. 2008 Apr;21(2):116-21.
5. Gelse K, Angele P, Behrens P, et al. Debridement in Focal Cartilage Damage of the knee. Systematical review of the literature and recommendations of the working group “clinical tissue regeneration” of the German Society of Orthopaedics and Trauma (DGOU). Z Orthop Unfall. 2018 Aug;156(4):423-435.
6. Lubowitz, JH. Partial-Thickness Articular Cartilage Defects: Evaluation and Treatment. Operative Techniques in Orthopaedics. 2006; 16(4), 227–231.
7. Uribe J W. The Use of Radiofrequency Devices for Chondral Debridement. Sports Medicine and Arthroscopy Review. 2003; 11(4), 214–221.

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.

Alford JW, Cole BJ. Cartilage restoration, part 1: basic science, historical perspective, patient evaluation, and treatment options. Am J Sports Med. 2005;33(2):295-306.

Contributor: Jin Cheng


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.

Osteoarthritis. Sci Rep. 2017;7(1):16214.

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.

https://my.clevelandclinic.org/health/diseases/12564-edema

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.

Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noel D. Mesenchymal stem cells derived

Contributor: Luca Ambrosio


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.

Goutallier D, Postel JM, Bernageau J, Lavau L, Voisin MC. Fatty infiltration of disrupted rotator cuff muscles. Rev Rhum Engl Ed. 1995 Jun;62(6):415-22. PMID: 7552205.

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.

1. Carballo C, Nakagawa Y, Sekiya I, Rodeo S. Basic science of articular cartilage. Clin Sports Med, 2017; 36 (3), 413-425.
2. Ross MH, Wojciech P (eds). Histology: a text and atlas: with correlated cell and molecular biology. 6th edn. Baltimore: Lippincott Williams and Wilkins, 2011.
3. Gartner LP, Hiatt JL. Color Textbook of Histology. 3rd edn. Philadelphia: Saunders, 2007.

Contributor: Theodorakys Marin

See also:

Cartilage


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.

Hunter DJ. Viscosupplementation for osteoarthritis of the knee. N Engl J Med.
2015;372(11):1040-1047.

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.

Yang J, Zhang YS, Yue K, Khademhosseini A. Cell-laden hydrogels for osteochondral and
cartilage tissue engineering. Acta Biomater. 2017;57:1-25.

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


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].

1. Jurgens, W.J., et al., Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue. Cytotherapy, 2009. 11(8): p. 1052-64.
2. Vinardell, T., et al., Composition-function relations of cartilaginous tissues engineered from chondrocytes and mesenchymal stem cells isolated from bone marrow and infrapatellar fat pad. J Tissue Eng Regen Med, 2011. 5(9): p. 673-83.
3. Vinardell, T., et al., A comparison of the functionality and in vivo phenotypic stability of cartilaginous tissues engineered from different stem cell sources. Tissue Eng Part A, 2012. 18(11-12): p. 1161-70.
4. Almeida, H.V., et al., Controlled release of transforming growth factor-beta3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells. Acta Biomater, 2014. 10(10): p. 4400-9.
5. Liu, Y., et al., Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions. Tissue Engineering Part A, 2014. 20(21-22): p. 3050-3062.
6. Browe, D.C., et al., Glyoxal cross-linking of solubilized extracellular matrix to produce highly porous, elastic, and chondro-permissive scaffolds for orthopedic tissue engineering. J Biomed Mater Res A, 2019. 107(10): p. 2222-2234.
7. Hindle, P., et al., The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells with Increased Chondrogenic Potential for Regenerative Medicine. Stem Cells Transl Med, 2017. 6(1): p. 77-87.

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.

Kadow T, Sowa G, Vo N, Kang JD. Molecular basis of intervertebral disc degeneration and
herniations: what are the important translational questions? Clin Orthop Relat Res.
2015;473(6):1903-1912.

Contributor: Luca Ambrosio


Ligament

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

https://www.merriam-webster.com/dictionary/ligament

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.

1. Behrens P, Bitter T, Kurz B, et al. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)–5-year follow-up. Knee 2006;13(3): 194–202. 

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.

1. Utsunomiya H, Gao X, Deng Z, et al. Improvement of Cartilage Repair With Biologically Regulated Marrow Stimulation by Blocking TGF-β1 in A Rabbit Osteochondral Defect Model. Orthop J Sports Med. 2019;7(7 suppl5):2325967119S00263. Published 2019 Jul 29. doi:10.1177/2325967119S00263

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.

1. Lennon O, Totlis T. Rehabilitation and return to play following meniscal repair. Oper Tech Sports Med 2017;25:194-207
2. Eberbach H, Zwingmann J, Hohloch L, Bode G, Maier D, Niemeyer P, Südkamp NP, Feucht MJ. Sport-specific outcomes after isolated meniscal repair: A systematic review. Knee Surg Sports Traumatol Arthrosc 2018;26:762-771.
3. Kopf S, Beaufils P, Hirschmann MT, Rotigliano N, Ollivier M, Pereira H, Verdonk R, Darabos N, Ntagiopoulos P, Dejour D, Seil R, Becker R. Management of traumatic meniscus tears: the 2019 ESSKA meniscus consensus. Knee Surg Sports Traumatol Arthrosc. 2020 Apr;28(4):1177-1194.
4. Totlis T, Haunschild ED, Otountzidis N, Stamou K, Condron NB, Tsikopoulos K, Cole BJ. Return-to-Sport Rate and Activity Level Are High Following Arthroscopic All-Inside Meniscal Repair With and Without Concomitant Anterior Cruciate Ligament Reconstruction: A Systematic Review. Arthroscopy. 2021 Mar 19

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.).

1. Gasperini Luca, Mano João F. and Reis Rui L. 2014. Natural polymers for the microencapsulation of cells. J. R. Soc. Interface. 11: 20140817.
2. Oblasi, RM. 2015. Cell microencapsulation with synthetic polymers. J Biomed Mater Res Part A 2015: 103A: 846- 859.

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.

1. Rodrigo JJ, Steadman JR, Silliman JF, Fulstone HA. Improvement of full-thickness chondral defect healing in the human knee after debridement and microfracture using continuous passive motion. Am J Knee Surg 1994; 7(3): 109-16. 
2. Weber AE, Locker PH, Mayer EN, et al. Clinical Outcomes After Microfracture of the Knee: Midterm Follow-up. Orthop J Sport Med. 2018;6(2):1-7. doi:10.1177/2325967117753572 
3. Erggelet C, Vavken P. Microfracture for the treatment of cartilage defects in the knee joint – A golden standard? J Clin Orthop Trauma. 2016;7(3):145-152. doi:10.1016/j.jcot.2016.06.015

Contributor: Erick Gutierrez Cota


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.

1. Caplan AI. MSCs: The Sentinel and Safe-Guards of Injury. J Cell Physiol. 2016; 231(7):1413-6.
2. Caplan AI. There is no “Stem Cell Mess”. Tissue Eng Part B Rev. 2019;25(4):291-293.
3. Caplan AI. Mesenchymal Stem Cells: Time to Change the Name. Stem Cells Transl Med. 2017; 6(6):1445-1451. 
4. Caplan AI. New MSC: MSCs as pericytes are sentinels and gatekeepers. J Orthop Res. 2017;35(6):1151-1159. 

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


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


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.

1. S Glyn-Jones, A J R Palmer, R Agricola, A J Price, T L Vincent, H Weinans, A J Carr, Osteoarthritis, The Lancet, Volume 386, Issue 9991, 2015, Pages 376-387, 
https://doi.org/10.1016/S0140-6736(14)60802-3.
2. Li G, Yin J, Gao J, Cheng TS, Pavlos NJ, Zhang C, Zheng MH. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther. 2013;15(6):223. doi: 10.1186/ar4405. PMID: 24321104; PMCID: PMC4061721.

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.

Gracitelli GC, Tirico LE, McCauley JC, Pulido PA, Bugbee WD. Fresh
Osteochondral Allograft Transplantation for Fractures of the Knee. Cartilage.
2017 Apr;8(2):155-161. doi: 10.1177/1947603516657640.

Gracitelli GC, Meric G, Pulido PA, McCauley JC, Bugbee WD. Osteochondral
Allograft Transplantation for Knee Lesions after Failure of Cartilage Repair
Surgery. Cartilage. 2015 Apr;6(2):98-105. doi: 10.1177/1947603514566298.

Gracitelli GC, Meric G, Briggs DT, Pulido PA, McCauley JC, Belloti JC, Bugbee 
WD. Fresh osteochondral allografts in the knee: comparison of primary
transplantation versus transplantation after failure of previous subchondral
marrow stimulation. Am J Sports Med. 2015 Apr;43(4):885-91.

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


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.

1. Arkady Rutkovskiy, Kåre-Olav Stensløkken, and Ingvar Jarle Vaage. (2016) Osteoblast Differentiation at a Glance. Med Sci Monit Basic Res., 22: 95-106
https://en.wikipedia.org/wiki/Ossification
https://www.merriam-webster.com/dictionary/osteogenesis

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].

1.           Gertner, J.M. & Root, L. Osteogenesis imperfecta. Orthop Clin North Am 21, 151-162 (1990).
2.           Forlino, A. & Marini, J.C. Osteogenesis imperfecta. Lancet 387, 1657-1671 (2016).
3.           Baitner, A.C., Maurer, S.G., Gruen, M.B. & Di Cesare, P.E. The genetic basis of the osteochondrodysplasias. Journal of pediatric orthopedics 20, 594-605 (2000).
4.           Cole, W.G. Etiology and pathogenesis of heritable connective tissue diseases. Journal of pediatric orthopedics 13, 392-403 (1993).
5.           Kocher, M.S. & Shapiro, F. Osteogenesis imperfecta. The Journal of the American Academy of Orthopaedic Surgeons 6, 225-236 (1998).
6.           Hanscom, D.A., et al. Osteogenesis imperfecta. Radiographic classification, natural history, and treatment of spinal deformities. The Journal of bone and joint surgery. American volume 74, 598-616 (1992).
7.           Van Dijk, F.S. & Sillence, D.O. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. American journal of medical genetics. Part A 164A, 1470-1481 (2014).
8.           Krakow, D. Skeletal dysplasias. Clin Perinatol 42, 301-319, viii (2015).
9.           Ward, L.M., et al. Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone 31, 12-18 (2002).
10.         van Dijk, F.S., et al. Complete COL1A1 allele deletions in osteogenesis imperfecta. Genetics in medicine : official journal of the American College of Medical Genetics 12, 736-741 (2010).
11.         Namazi, H. Intravenous pamidronate therapy in osteogenesis imperfecta: response to treatment and factors influencing outcome: a novel molecular mechanism. Journal of pediatric orthopedics 29, 650-651 (2009).
12.         Wenger, D.R., Ward, W.T. & Herring, J.A. Legg-Calve-Perthes disease. The Journal of bone and joint surgery. American volume 73, 778-788 (1991).
13.         Orcel, P. & Beaudreuil, J. Bisphosphonates in bone diseases other than osteoporosis. Joint Bone Spine 69, 19-27 (2002).
14.         Borumandi, F., Aghaloo, T., Cascarini, L., Gaggl, A. & Fasanmade, K. Anti-resorptive Drugs and their Impact on Maxillofacial Bone among Cancer Patients. Anticancer Agents Med Chem 15, 736-743 (2015).
15.         Burnei, G., Vlad, C., Georgescu, I., Gavriliu, T.S. & Dan, D. Osteogenesis imperfecta: diagnosis and treatment. The Journal of the American Academy of Orthopaedic Surgeons 16, 356-366 (2008).
16.         Harrington, J., Sochett, E. & Howard, A. Update on the evaluation and treatment of osteogenesis imperfecta. Pediatric clinics of North America 61, 1243-1257 (2014).
17.         Esposito, P. & Plotkin, H. Surgical treatment of osteogenesis imperfecta: current concepts. Curr Opin Pediatr 20, 52-57 (2008).

Contributor: Ava Brozovich


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.

1. Bonasia DE, Governale G, Spolaore S, Rossi R, Amendola A. High tibial osteotomy. Curr Rev Musculoskelet Med. 2014 Dec; 7(4):292-301.
2. Rossi R, Bonasia DE, Amendola A. The role of high tibial osteotomy in the varus knee. J Am Acad Orthop Surg. 2011 Oct;19(10):590-9. Review
3. Pilone C, rosso F, Cottino U, Rossi R, Bonasia DE. Lateral opening wedge distal femoral osteotomy for lateral compartment arthrosis/overload. Clin Sports Med 2019 Jul;38(3):351-359. Epub 2019 Mar 26. Review.
4. Leong NL, Southworth TM, Cole BJ. Distal Femoral Osteotomy and Lateral Meniscus Allograft Transplant. Clin Sports Med. 2019 Jul;38(3):387-399. 

Contributor: Brian Lau


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.

[1] S.M. Kurtz, Chapter 1 - An Overview of PEEK Biomaterials, PEEK Biomaterials Handbook, William Andrew Publishing, Oxford, 2012, pp. 1-7.

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.

[1] S.A. Maas, B.J. Ellis, G.A. Ateshian, J.A. Weiss, FEBio: Finite Elements for Biomechanics, J. Biomech. Eng. Asme. 134 (2012). doi:10.1115/1.4005694.
[2] M.A. Accardi, D. Dini, P.M. Cann, Experimental and numerical investigation of the behaviour of articular cartilage under shear loading-Interstitial fluid pressurisation and lubrication mechanisms, Tribol. Int. 44 (2011) 565–578. doi:10.1016/j.triboint.2010.09.009.
[3] D.H. Cortes, J.T. Nathan, J.F. DeLucca, E.M. Dawn, Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering, J. Biomech. 47 2088–2094.
[4] V.C. Mow, S.C. Kuei, W.M. Lai, C.G. Armstrong, Biphasic Creep and Stress-Relaxation of Articular-Cartilage in Compression - Theory and Experiments, J. Biomech. Eng. Asme. 102 (1980) 73–84.
[5] C.W. McCutchen, The frictional properties of animal joints, Wear. 5 (1962) 1–17. doi:10.1016/0043-1648(62)90176-X.
[6] G.A. Ateshian, V. Rajan, N.O. Chahine, C.C. Guterl, C.T. Hung, Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena, J. Biomech. Eng. 131 (2009) 061003. doi:10.1115/1.3118773.
[7] A.C. Moore, J.F. DeLucca, D.M. Elliott, D.L. Burris, Quantifying Cartilage Contact Modulus, Tension Modulus, and Permeability With Hertzian Biphasic Creep., J. Tribol. 138 (2016) 414051–414057. doi:10.1115/1.4032917.

Contributor: Axel Moore


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.

DOI: 10.2106/JBJS.18.00005

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


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.

1. Cserjesi P, Brown D, Ligon KL, Lyons GE, Copeland NG, Gilbert DJ, Jenkins NA, Olson EN (April 1995). "Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis". Development. 121 (4): 1099–110
2. Brent AE, Schweitzer R, Tabin CJ (April 2003). "A somitic compartment of tendon progenitors". Cell. 113 (2): 235–48. doi:10.1016/S0092-8674(03)00268-X
3. Murchison ND1, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R., Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons., Development. 2007 Jul;134(14):2697-708, PMID: 17567668 DOI: 10.1242/dev.001933

Contributor: Mariya Hadzhinikolova


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.

https://www.medicinenet.com/script/main/art.asp?articlekey=10597

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.

Ramakrishna, H., Li, T., He, T. et al. Tissue engineering a tendon-bone junction with biodegradable braided scaffolds. Biomater Res 23, 11 (2019). https://doi.org/10.1186/s40824-019-0160-3

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.

1. Shukunami C, Oshima Y, Hiraki Y (February 2001). "Molecular cloning of tenomodulin, a novel chondromodulin-I related gene". Biochemical and Biophysical Research Communications. 280 (5): 1323–7. doi:10.1006/bbrc.2001.4271
2. Brandau O, Meindl A, Fässler R, Aszódi A (May 2001). "A novel gene, tendin, is strongly expressed in tendons and ligaments and shows high homology with chondromodulin-I". Developmental Dynamics. 221 (1): 72–80. doi:10.1002/dvdy.1126. PMID 11357195
3. Dex, S., Lin, D., Shukunami, C., & Docheva, D. (2016). TENOgenic MODULating INsider factor: systematic assessment on the functions of tenomodulin gene. Gene, 587(1), 1–17. doi:10.1016/j.gene.2016.04.051 

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


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.

1. Ahmed TA, Hincke MT. Strategies for articular cartilage lesion repair and functional restoration. Tissue Eng Part B Rev. 2010;16(3):305-329.
2. Nehrer S, Spector M, Minas T. Histologic analysis of tissue after failed cartilage repair procedures. Clin Orthop Relat Res. 1999(365):149-162.
3. Tang QO, Shakib K, Heliotis M, et al. TGF-beta3: A potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther. 2009;9(6):689-701.

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).

1. Katz, N.P., Paillard, F.C. & Ekman, E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surg Res 10, 24 (2015). https://doi.org/10.1186/s13018-014-0144-x
2. Karabis, A., Nikolakopoulos, S., Pandhi, S. et al. High correlation of VAS pain scores after 2 and 6 weeks of treatment with VAS pain scores at 12 weeks in randomised controlled trials in rheumatoid arthritis and osteoarthritis: meta-analysis and implications. Arthritis Res Ther 18, 73 (2016). https://doi.org/10.1186/s13075-016-0972-7

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.

Hunter DJ. Viscosupplementation for osteoarthritis of the knee. N Engl J Med.

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.

1. Davies JE, Walker JT, Keating A. Concise review: wharton’s jelly: the rich, but enigmatic, source of mesenchymal stromal cells. Stem Cells Transl Med. 2017 Jul;6(7):1620-1630. Doi: 10.1002/sctm.16-0492
2. Joerger-Messerli MS, Marx C, Oppliger B, et al. Mesenchymal stem cells from wharton’s jelly and amniotic fluid. Best Pract Res Clin Obstet Gynaecol. 2016;31:30-44. Doi: 10.1016/j.bpobgyn.2015.07.006

Contributor: Josiah Valk