Tendon explant models for physiologically relevant invitro study of tissue biology – a perspective

References

• Kaux JF, Forthomme B, Goff CL, Crielaard J-M, Croisier J-L. Current opinions on tendinopathy. J Sports Sci Med. 2011;10(2):238–253.
   PubMed Web of Science ®Google Scholar
• Scott A, Backman LJ, Speed C. Tendinopathy: update on pathophysiology. J Orthop Sports Phys Ther. 2015;45(11):833–841. doi:10.2519/jospt.2015.5884.
   PubMed Web of Science ®Google Scholar
• Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med. 2003;22(4):675–692. doi:10.1016/S0278-5919(03)00004-8.
   PubMed Web of Science ®Google Scholar
• McCreesh K, Lewis J. Continuum model of tendon pathology - where are we now? Int J Exp Pathol. 2013;94(4):242–247. doi:10.1111/iep.12029.
   PubMed Web of Science ®Google Scholar
• Hopkins C, Fu S-C, Chua E, Hu X, Rolf C, Mattila VM, Qin L, Yung PS-H, Chan K-M. Critical review on the socio-economic impact of tendinopathy. Asia Pac J Sports Med Arthrosc Rehabil Technol. 2016;4:9–20. doi:10.1016/j.asmart.2016.01.002.
   PubMed Web of Science ®Google Scholar
• Riley G. Tendinopathy–from basic science to treatment. Nat Clin Pract Rheumatol. 2008;4(2):82–89. doi:10.1038/ncprheum0700.
   PubMedGoogle Scholar
• Ranger TA, Wong AMY, Cook JL, Gaida JE. Is there an association between tendinopathy and diabetes mellitus? A systematic review with meta-analysis. Br J Sports Med. 2016;50(16):982–989. doi:10.1136/bjsports-2015-094735.
   PubMed Web of Science ®Google Scholar
• Burner TW, Rosenthal AK. Diabetes and rheumatic diseases. Curr Opin Rheumatol. 2009;21(1):50–54. doi:10.1097/BOR.0b013e32831bc0c4.
   PubMed Web of Science ®Google Scholar
• Gaida JE, Ashe MC, Bass SL, Cook JL. Is adiposity an under-recognized risk factor for tendinopathy? A systematic review. Arthritis Rheum. 2009;61(6):840–849. doi:10.1002/art.v61:6.
   PubMed Web of Science ®Google Scholar
• Abate M, Schiavone C, Salini V, Andia I. Occurrence of tendon pathologies in metabolic disorders. Rheumatology (Oxford). 2013;52(4):599–608. doi:10.1093/rheumatology/kes395.
   PubMed Web of Science ®Google Scholar
• Oliva F, Piccirilli E, Berardi AC, Frizziero A, Tarantino U, Maffulli N. Hormones and tendinopathies: the current evidence. Br Med Bull. 2016;117(1):39–58. doi:10.1093/bmb/ldv054.
   PubMed Web of Science ®Google Scholar
• Xu Y, Murrell GA. The basic science of tendinopathy. Clin Orthop Relat Res. 2008;466(7):1528–1538. doi:10.1007/s11999-008-0286-4.
   PubMed Web of Science ®Google Scholar
• Kaeding C, Best TM. Tendinosis: pathophysiology and nonoperative treatment. Sports Health. 2009;1(4):284–292. doi:10.1177/1941738109337778.
   PubMedGoogle Scholar
• Millar NL, Murrell GA, McInnes IB. Inflammatory mechanisms in tendinopathy - towards translation. Nat Rev Rheumatol. 2017;13(2):110–122. doi:10.1038/nrrheum.2016.213.
   PubMed Web of Science ®Google Scholar
• Andarawis-Puri N, Flatow EL, Soslowsky LJ. Tendon basic science: development, repair, regeneration, and healing. J Orthop Res. 2015;33(6):780–784. doi:10.1002/jor.22869.
   PubMed Web of Science ®Google Scholar
• Docheva D, Müller SA, Majewski M, Evans CH. Biologics for tendon repair. Adv Drug Deliv Rev. 2015;84:222–239. doi:10.1016/j.addr.2014.11.015.
   PubMed Web of Science ®Google Scholar
• Handsfield GG, Slane LC, Screen HR. Nomenclature of the tendon hierarchy: an overview of inconsistent terminology and a proposed size-based naming scheme with terminology for multi-muscle tendons. J Biomech. 2016. doi:10.1016/j.jbiomech.2016.06.028.
   Web of Science ®Google Scholar
• Svensson RB, Herchenhan A, Starborg T, Larsen M, Kadler KE, Qvortrup K, Magnusson SP. Evidence of structurally continuous collagen fibrils in tendon. Acta Biomater. 2017. doi:10.1016/j.actbio.2017.01.006.
   PubMed Web of Science ®Google Scholar
• Thorpe CT, Birch HL, Clegg PD, Screen HRC. Tendon physiology and mechanical behavior: structure-function relationships. In: Gomes M, Reis R, Rodrigues, M, editors. Tendon regeneration understanding tissue physiology and development to engineer functional substitutes. London (UK): Elsevier; 2015. p. 3–39.
   Google Scholar
• Williams I, McCullagh K, Silver I. The distribution of types I and III collagen and fibronectin in the healing equine tendon. Connect Tissue Res. 1984;12(3–4):211–227. doi:10.3109/03008208409013684.
   PubMed Web of Science ®Google Scholar
• Riley G, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL. Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis. 1994;53(6):359–366. doi:10.1136/ard.53.6.359.
   PubMed Web of Science ®Google Scholar
• Pingel J, Lu Y, Starborg T, Fredberg U, Langberg H, Nedergaard A, Weis M, Eyre D, Kjaer M, Kadler KE. 3-D ultrastructure and collagen composition of healthy and overloaded human tendon: evidence of tenocyte and matrix buckling. J Anat. 2014;224(5):548–555. doi:10.1111/joa.2014.224.issue-5.
   PubMed Web of Science ®Google Scholar
• Birk DE, Fitch JM, Babiarz JP, Doane KJ, Linsenmayer TF. Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J Cell Sci. 1990;95(4):649–657.
   PubMed Web of Science ®Google Scholar
• Fichard A, Kleman J-P, Ruggiero F. Another look at collagen V and XI molecules. Matrix Biol. 1995;14(7):515–531. doi:10.1016/S0945-053X(05)80001-0.
   PubMed Web of Science ®Google Scholar
• Wenstrup RJ, Florer JB, Brunskill EW, Bell SM, Chervoneva I, Birk DE. Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem. 2004;279(51):53331–53337. doi:10.1074/jbc.M409622200.
   PubMed Web of Science ®Google Scholar
• Wenstrup RJ, Smith SM, Florer JB, Zhang G, Beason DP, Seegmiller RE, Soslowsky LJ, Birk DE. Regulation of collagen fibril nucleation and initial fibril assembly involves coordinate interactions with collagens V and XI in developing tendon. J Biol Chem. 2011;286(23):20455–20465. doi:10.1074/jbc.M111.223693.
   PubMed Web of Science ®Google Scholar
• Sun M, Connizzo BK, Adams SM, Freedman BR, Wenstrup RJ, Soslowsky LJ, Birk DE. Targeted deletion of collagen V in tendons and ligaments results in a classic Ehlers-Danlos syndrome joint phenotype. Am J Pathol. 2015;185(5):1436–1447. doi:10.1016/j.ajpath.2015.01.031.
   PubMed Web of Science ®Google Scholar
• Thakkar D, Grant TM, Hakimi O, Carr AJ. Distribution and expression of type VI collagen and elastic fibers in human rotator cuff tendon tears. Connect Tissue Res. 2014;55(5–6):397–402. doi:10.3109/03008207.2014.959119.
   PubMed Web of Science ®Google Scholar
• Banos CC, Thomas AH, Kuo CK. Collagen fibrillogenesis in tendon development: current models and regulation of fibril assembly. Birth Defects Res Part C: Embryo Today: Rev. 2008;84(3):228–244. doi:10.1002/bdrc.v84:3.
   PubMedGoogle Scholar
• Thorpe CT, Birch HL, Clegg PD, Screen HRC. The role of the non-collagenous matrix in tendon function. Int J Exp Pathol. 2013;94(4):248–259. doi:10.1111/iep.12027.
   PubMed Web of Science ®Google Scholar
• Taye N, Karoulias SZ, Hubmacher D. The “other” 15–40%: the role of non-collagenous extracellular matrix proteins and minor collagens in tendon. J Orthop Res. 2019. doi:10.1002/jor.24440.
   PubMed Web of Science ®Google Scholar
• Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports. 2000;10(6):312–320. doi:10.1034/j.1600-0838.2000.010006312.x.
   PubMed Web of Science ®Google Scholar
• Banes AJ, Link GW, Bevin AG, Peterson HD, Gillespie Y, Bynum D, Watts S, Dahners L. Tendon synovial cells secrete fibronectin in vivo and in vitro. J Orthop Res. 1988;6(1):73–82. doi:10.1002/jor.1100060110.
   PubMed Web of Science ®Google Scholar
• Jozsa L, Lehto M, Kannus P, Kvist M, Reffy A, Vieno T, Järvinen M, Demel S, Elek E. Fibronectin and laminin in Achilles tendon. Acta Orthop Scand. 1989;60(4):469–471. doi:10.3109/17453678909149322.
   PubMed Web of Science ®Google Scholar
• Smith R, Gerard M, Dowling B, Dart AJ, Birch HL, Goodship AE. Correlation of cartilage oligomeric matrix protein (COMP) levels in equine tendon with mechanical properties: a proposed role for COMP in determining function‐specific mechanical characteristics of locomotor tendons. Equine Vet J. 2002;34(S34):241–244.
   Google Scholar
• Martin J, Mehr D, Pardubsky PD, Buckwalter JA. The role of tenascin‐C in adaptation of tendons to compressive loading. Biorheology. 2003;40(1, 2, 3):321–329.
   PubMed Web of Science ®Google Scholar
• Kohrs RT, Zhao C, Sun YL, Jay GD, Zhang L, Warman ML, An KN, Amadio PC. Tendon fascicle gliding in wild type, heterozygous, and lubricin knockout mice. J Orthop Res. 2011;29(3):384–389. doi:10.1002/jor.21247.
   PubMed Web of Science ®Google Scholar
• Frolova EG, Drazba J, Krukovets I, Kostenko V, Blech L, Harry C, Vasanji A, Drumm C, Sul P, Jenniskens GJ, Plow EF, Stenina-Adognravi O. Control of organization and function of muscle and tendon by thrombospondin-4. Matrix Biol. 2014;37:35–48. doi:10.1016/j.matbio.2014.02.003.
   PubMed Web of Science ®Google Scholar
• Järvinen M, Kannus P, Kvist M, Isola J, Lehto M, Jozsa L. Macromolecular composition of the myotendinous junction. Exp Mol Pathol. 1991;55(3):230–237. doi:10.1016/0014-4800(91)90003-G.
   PubMed Web of Science ®Google Scholar
• Merrilees MJ, Flint MH. Ultrastructural study of tension and pressure zones in a rabbit flexor tendon. Am J Anat. 1980;157(1):87–106.
   PubMedGoogle Scholar
• Birk DE, Trelstad RL. Extracellular compartments in tendon morphogenesis: collagen fibril, bundle, and macroaggregate formation. J Cell Biol. 1986;103(1):231–240. doi:10.1083/jcb.103.1.231.
   PubMed Web of Science ®Google Scholar
• Best KT, Loiselle AE. Scleraxis lineage cells contribute to organized bridging tissue during tendon healing and identify a subpopulation of resident tendon cells. FASEB J. 2019;33(7):8578–8587. doi:10.1096/fj.201900130RR.
   PubMed Web of Science ®Google Scholar
• Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ. Analysis of the tendon cell fate using scleraxis, a specific marker for tendons and ligaments. Development. 2001;128(19):3855–3866.
   PubMed Web of Science ®Google Scholar
• Delgado Caceres M, Pfeifer CG, Docheva D. Understanding tendons: lessons from transgenic mouse models. Stem Cells Dev. 2018;27(17):1161–1174. doi:10.1089/scd.2018.0121.
   PubMed Web of Science ®Google Scholar
• Eadie AL, Titus AJ, Brunt KR. Getting to the heart of myofibroblast differentiation: implications for scleraxis in ECM remodeling and therapeutic targeting. Am J Physiol Heart Circ Physiol. 2018;315(5):H1232–H1235. doi:10.1152/ajpheart.00381.2018.
   PubMed Web of Science ®Google Scholar
• Yin Z, Hu JJ, Yang L, Zheng ZF, An CR, Wu BB, Zhang C, Shen WL, Liu HH, Chen JL, Heng BC. Single-cell analysis reveals a nestin+ tendon stem/progenitor cell population with strong tenogenic potentiality. Sci Adv. 2016;2(11):e1600874. doi:10.1126/sciadv.1600874.
   PubMed Web of Science ®Google Scholar
• Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJF, Smith RDJ, Wheway K, Watkins B, Roche L, Carr AJ. Inflammation activation and resolution in human tendon disease. Sci Transl Med. 2015;7(311):311ra173–311ra173. doi:10.1126/scitranslmed.aac4269.
   PubMed Web of Science ®Google Scholar
• Swanson JB, De Micheli AJ, Disser NP, Martinez LM, Walker NR, Cosgrove BD, Mendias CL. A single-cell transcriptional atlas identifies extensive heterogeneity in the cellular composition of tendons. BioRXiv. 2019.
   Google Scholar
• Eliasson P, Andersson T, Hammerman M, Aspenberg P. Primary gene response to mechanical loading in healing rat Achilles tendons. J Appl Physiol (1985). 2013;114(11):1519–1526. doi:10.1152/japplphysiol.01500.2012.
   PubMed Web of Science ®Google Scholar
• Arnoczky SP, Lavagnino M, Whallon JH, Hoonjan A. In situ cell nucleus deformation in tendons under tensile load; a morphological analysis using confocal laser microscopy. J Orthop Res. 2002;20(1):29–35. doi:10.1016/S0736-0266(01)00080-8.
   PubMed Web of Science ®Google Scholar
• Andersson T, Eliasson P, Hammerman M, Sandberg O, Aspenberg P. Low-level mechanical stimulation is sufficient to improve tendon healing in rats. J Appl Physiol (1985). 2012;113(9):1398–1402. doi:10.1152/japplphysiol.00491.2012.
   PubMed Web of Science ®Google Scholar
• Freedman BR, Rodriguez AB, Leiphart RJ, Newton JB, Ban E, Sarver JJ, Mauck RL, Shenoy VB, Soslowsky LJ. Dynamic loading and tendon healing affect multiscale tendon properties and ECM stress transmission. Sci Rep. 2018;8(1):10854. doi:10.1038/s41598-018-29060-y.
   PubMed Web of Science ®Google Scholar
• Arnoczky SP, Lavagnino M, Egerbacher M. The mechanobiological aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation of tendon cells? Int J Exp Pathol. 2007;88(4):217–226. doi:10.1111/j.1365-2613.2007.00548.x.
   PubMed Web of Science ®Google Scholar
• Snedeker JG, Gautieri A. The role of collagen crosslinks in ageing and diabetes - the good, the bad, and the ugly. Muscles Ligaments Tendons J. 2014;4(3):303–308. doi:10.32098/mltj.03.2014.07.
   PubMedGoogle Scholar
• Nourissat G, Berenbaum F, Duprez D. Tendon injury: from biology to tendon repair. Nat Rev Rheumatol. 2015;11(4):223. doi:10.1038/nrrheum.2015.26.
   PubMed Web of Science ®Google Scholar
• Killian ML, Cavinatto L, Galatz LM, Thomopoulos S. The role of mechanobiology in tendon healing. J Shoulder Elbow Surg. 2012;21(2):228–237. doi:10.1016/j.jse.2011.11.002.
   PubMed Web of Science ®Google Scholar
• Lebaschi A, Deng X-H, Zong J, Cong G-T, Carballo CB, Album ZM, Camp C, Rodeo SA. Animal models for rotator cuff repair. Ann N Y Acad Sci. 2016;1383(1):43–57. doi:10.1111/nyas.2016.1383.issue-1.
   PubMed Web of Science ®Google Scholar
• Bottagisio M, Lovati AB. A review on animal models and treatments for the reconstruction of Achilles and flexor tendons. J Mater Sci Mater Med. 2017;28(3):45. doi:10.1007/s10856-017-5858-y.
   PubMed Web of Science ®Google Scholar
• Brehm MA, Shultz LD, Luban J, Greiner DL. Overcoming current limitations in humanized mouse research. J Infect Dis. 2013;208(Suppl 2):S125–30. doi:10.1093/infdis/jit319.
   PubMed Web of Science ®Google Scholar
• Nunan R, Harding KG, Martin P. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Dis Model Mech. 2014;7(11):1205–1213. doi:10.1242/dmm.016782.
   PubMed Web of Science ®Google Scholar
• Marr C, McMillan I, Boyd JS, Wright NG, Murray M. Ultrasonographic and histopathological findings in equine superficial digital flexor tendon injury. Equine Vet J. 1993;25(1):23–29. doi:10.1111/evj.1993.25.issue-1.
   PubMed Web of Science ®Google Scholar
• Muir P, Johnson K. Supraspinatus and biceps brachii tendinopathy in dogs. J Small Anim Pract. 1994;35(5):239–243. doi:10.1111/j.1748-5827.1994.tb03268.x.
   Web of Science ®Google Scholar
• Smith MM, Sakurai G, Smith SM, Young AA, Melrose J, Stewart CM, Appleyard RC, Peterson JL, Gillies RM, Dart AJ, Sonnabend DH, Little CB. Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain. Arthritis Rheum. 2008;58(4):1055–1066. doi:10.1002/art.23388.
   PubMed Web of Science ®Google Scholar
• Hast M, Zuskov A, Soslowsky L. The role of animal models in tendon research. Bone Joint Res. 2014;3(6):193–202. doi:10.1302/2046-3758.36.2000281.
   PubMed Web of Science ®Google Scholar
• Vigano M, Perucca Orfei C, Colombini A, Stanco D, Randelli P, Sansone V, de Girolamo L. Different culture conditions affect the growth of human tendon stem/progenitor cells (TSPCs) within a mixed tendon cells (TCs) population. J Exp Orthop. 2017;4(1):8. doi:10.1186/s40634-017-0082-8.
   PubMedGoogle Scholar
• Russell WMS, Burch RL, Hume CW. The principles of humane experimental technique. London (UK): Methuen; 1959.
   Google Scholar
• Kastelic J, Galeski A, Baer E. The multicomposite structure of tendon. Connect Tissue Res. 1978;6(1):11–23. doi:10.3109/03008207809152283.
   PubMed Web of Science ®Google Scholar
• Robinson PS, Huang T-F, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ. Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice. J Biomech Eng. 2005;127(1):181–185. doi:10.1115/1.1835363.
   PubMed Web of Science ®Google Scholar
• Sasaki N, Odajima S. Elongation mechanism of collagen fibrils and force-strain relations of tendon at each level of structural hierarchy. J Biomech. 1996;29(9):1131–1136. doi:10.1016/0021-9290(96)00024-3.
   PubMed Web of Science ®Google Scholar
• Fessel G, Snedeker JG. Evidence against proteoglycan mediated collagen fibril load transmission and dynamic viscoelasticity in tendon. Matrix Biol. 2009;28(8):503–510. doi:10.1016/j.matbio.2009.08.002.
   PubMed Web of Science ®Google Scholar
• Rigozzi S, Mueller R, Snedeker JG. Collagen fibril morphology and mechanical properties of the Achilles tendon in two inbred mouse strains. J Anat. 2010;216(6):724–731. doi:10.1111/j.1469-7580.2010.01225.x.
   PubMed Web of Science ®Google Scholar
• Li Y, Fessel G, Georgiadis M, Snedeker JG. Advanced glycation end-products diminish tendon collagen fiber sliding. Matrix Biol. 2013;32(3–4):169–177. doi:10.1016/j.matbio.2013.01.003.
   PubMed Web of Science ®Google Scholar
• Gautieri A, Passini FS, Silván U, Guizar-Sicairos M, Carimati G, Volpi P, Moretti M, Schoenhuber H, Redaelli A, Berli M, Snedeker JG. Advanced glycation end-products: mechanics of aged collagen from molecule to tissue. Matrix Biol. 2017; 59:95–108. doi:10.1016/j.matbio.2016.09.001.
   Web of Science ®Google Scholar
• Szczesny SE, Elliott DM. Interfibrillar shear stress is the loading mechanism of collagen fibrils in tendon. Acta Biomater. 2014;10(6):2582–2590. doi:10.1016/j.actbio.2014.01.032.
   PubMed Web of Science ®Google Scholar
• Thorpe CT, Riley GP, Birch HL, Clegg PD, Screen HRC. Effect of fatigue loading on structure and functional behaviour of fascicles from energy-storing tendons. Acta Biomater. 2014;10(7):3217–3224. doi:10.1016/j.actbio.2014.04.008.
   PubMed Web of Science ®Google Scholar
• Szczesny SE, Aeppli C, David A, Mauck RL. Fatigue loading of tendon results in collagen kinking and denaturation but does not change local tissue mechanics. J Biomech. 2018;71:251–256. doi:10.1016/j.jbiomech.2018.02.014.
   PubMed Web of Science ®Google Scholar
• Snedeker JG, Foolen J. Tendon injury and repair - A perspective on the basic mechanisms of tendon disease and future clinical therapy. Acta Biomater. 2017;63:18–36. doi:10.1016/j.actbio.2017.08.032.
   PubMed Web of Science ®Google Scholar
• Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res. 2007;25(2):230–240. doi:10.1002/(ISSN)1554-527X.
   PubMed Web of Science ®Google Scholar
• Ikeda J, Zhao C, Moran SL, An K-N, Amadio PC. Effects of synovial interposition on healing in a canine tendon explant culture model. J Hand Surg Am. 2010;35(7):1153–1159. doi:10.1016/j.jhsa.2010.03.023.
   PubMed Web of Science ®Google Scholar
• Costa-Almeida R, Berdecka D, Rodrigues MT, Reis RL, Gomes ME. Tendon explant cultures to study the communication between adipose stem cells and native tendon niche. J Cell Biochem. 2018;119(4):3653–3662. doi:10.1002/jcb.v119.4.
   PubMed Web of Science ®Google Scholar
• Connizzo BK, Grodzinsky AJ. Release of pro-inflammatory cytokines from muscle and bone causes tenocyte death in a novel rotator cuff in vitro explant culture model. Connect Tissue Res. 2018;59:423–436. doi:10.1080/03008207.2018.1439486.
   PubMed Web of Science ®Google Scholar
• Fessel G, Cadby J, Wunderli S, van Weeren R, Snedeker JG. Dose and time dependent effects of genipin cross-linking on cell viability and tissue mechanics - toward clinical application for tendon repair. Acta Biomater. 2014;10(5):1897–1906. doi:10.1016/j.actbio.2013.12.048.
   PubMed Web of Science ®Google Scholar
• Abrahamsson SO, Lundborg G, Lohmander LS. Recombinant human insulin‐like growth factor‐I stimulates in vitro matrix synthesis and cell proliferation in rabbit flexor tendon. J Orthop Res. 1991;9(4):495–502. doi:10.1002/jor.1100090405.
   PubMed Web of Science ®Google Scholar
• Yoshikawa Y, Abrahamsson SO. Dose-related cellular effects of platelet-derived growth factor-BB differ in various types of rabbit tendons in vitro. Acta Orthop Scand. 2001;72(3):287–292. doi:10.1080/00016470152846646.
   PubMed Web of Science ®Google Scholar
• Wong MW, Lui WT, Chuen Fu S, Man Lee K. The effect of glucocorticoids on tendon cell viability in human tendon explants. Acta Orthop. 2009;80(3):363–367. doi:10.3109/17453670902988386.
   PubMed Web of Science ®Google Scholar
• Wang T, Lin Z, Ni M, Thien C, Day RE, Gardiner B, Rubenson J, Kirk TB, Smith DW, Wang A, Lloyd DG. Cyclic mechanical stimulation rescues Achilles tendon from degeneration in a bioreactor system. J Orthop Res. 2015;33(12):1888–1896.
   PubMed Web of Science ®Google Scholar
• Wang T, Lin Z, Day RE, Gardiner B, Landao-Bassonga E, Rubenson J, Kirk TB, Smith DW, Lloyd DG, Hardisty G, Wang A, Zheng Q, Zheng MH. Programmable mechanical stimulation influences tendon homeostasis in a bioreactor system. Biotechnol Bioeng. 2013;110(5):1495–1507. doi:10.1002/bit.v110.5.
   PubMed Web of Science ®Google Scholar
• Adekanmbi I, Franklin S, Thompson MS. A novel in vitro loading system for high frequency loading of cultured tendon fascicles. Med Eng Phys. 2013;35(2):205–210. doi:10.1016/j.medengphy.2012.08.015.
   PubMed Web of Science ®Google Scholar
• Abreu EL, Leigh D, Derwin KA. Effect of altered mechanical load conditions on the structure and function of cultured tendon fascicles. J Orthop Res. 2008;26(3):364–373. doi:10.1002/(ISSN)1554-527X.
   PubMed Web of Science ®Google Scholar
• Pörtner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM. Bioreactor design for tissue engineering. J Biosci Bioeng. 2005;100(3):235–245. doi:10.1263/jbb.100.235.
   PubMed Web of Science ®Google Scholar
• Youngstrom DW, Rajpar I, Kaplan DL, Barrett JG. A bioreactor system for in vitro tendon differentiation and tendon tissue engineering. J Orthop Res. 2015;33(6):911–918. doi:10.1002/jor.22848.
   PubMed Web of Science ®Google Scholar
• Hannafin JA, Arnoczky SP. Effect of cyclic and static tensile loading on water content and solute diffusion in canine flexor tendons: an in vitro study. J Orthop Res. 1994;12(3):350–356. doi:10.1002/(ISSN)1554-527X.
   PubMed Web of Science ®Google Scholar
• Abousleiman RI, Reyes Y, McFetridge P, Sikavitsas V. Tendon tissue engineering using cell-seeded umbilical veins cultured in a mechanical stimulator. Tissue Eng Part A. 2008;15(4):787–795. doi:10.1089/ten.tea.2008.0102.
   Web of Science ®Google Scholar
• Wunderli SL, Widmer J, Amrein N, Foolen J, Silvan U, Leupin O, Snedeker JG. Minimal mechanical load and tissue culture conditions preserve native cell phenotype and morphology in tendon-a novel ex vivo mouse explant model. J Orthop Res. 2018;36(5):1383–1390. doi:10.1002/jorr.v36.5.
   PubMed Web of Science ®Google Scholar
• Hamilton B, Purdam C. Patellar tendinosis as an adaptive process: a new hypothesis. Br J Sports Med. 2004;38(6):758–761. doi:10.1136/bjsm.2003.005157.
   PubMed Web of Science ®Google Scholar
• Almekinders LC, Weinhold PS, Maffulli N. Compression etiology in tendinopathy. Clin Sports Med. 2003;22(4):703–710. doi:10.1016/S0278-5919(03)00067-X.
   PubMed Web of Science ®Google Scholar
• Szczesny SE, Caplan JL, Pedersen P, Elliott DM. Quantification of interfibrillar shear stress in aligned soft collagenous tissues via notch tension testing. Sci Rep. 2015;5:14649. doi:10.1038/srep14649.
   PubMed Web of Science ®Google Scholar
• Carpenter JE, Flanagan CL, Thomopoulos S, Yian EH, Soslowsky LJ. The effects of overuse combined with intrinsic or extrinsic alterations in an animal model of rotator cuff tendinosis. Am J Sports Med. 1998;26(6):801–807. doi:10.1177/03635465980260061101.
   PubMed Web of Science ®Google Scholar
• Lee AH, Elliott DM. Multi-scale loading and damage mechanisms of plantaris and rat tail tendons. J Orthop Res. 2019;37:1827–1837. doi:10.1002/jorr.v37.8.
   Web of Science ®Google Scholar
• Szczesny SE, Fetchko KL, Dodge GR, Elliott DM. Evidence that interfibrillar load transfer in tendon is supported by small diameter fibrils and not extrafibrillar tissue components. J Orthop Res. 2017;35:2127–2134. doi:10.1002/jor.v35.10.
   PubMed Web of Science ®Google Scholar
• Screen HR, Shelton JC, Chhaya VH, Kayser MV, Bader DL, Lee DA. The influence of noncollagenous matrix components on the micromechanical environment of tendon fascicles. Ann Biomed Eng. 2005;33(8):1090–1099. doi:10.1007/s10439-005-5777-9.
   PubMed Web of Science ®Google Scholar
• Screen HR, Lee DA, Bader DL, Shelton JC. An investigation into the effects of the hierarchical structure of tendon fascicles on micromechanical properties. Proc Inst Mech Eng H. 2004;218(2):109–119. doi:10.1243/095441104322984004.
   PubMed Web of Science ®Google Scholar
• Flick J, Devkota A, Tsuzaki M, Almekinders L, Weinhold P. Cyclic loading alters biomechanical properties and secretion of PGE2 and NO from tendon explants. Clin Biomech (Bristol, Avon). 2006;21(1):99–106. doi:10.1016/j.clinbiomech.2005.08.008.
   PubMed Web of Science ®Google Scholar
• Devkota AC, Tsuzaki M, Almekinders LC, Banes AJ, Weinhold PS. Distributing a fixed amount of cyclic loading to tendon explants over longer periods induces greater cellular and mechanical responses. J Orthop Res. 2007;25(8):1078–1086. doi:10.1002/(ISSN)1554-527X.
   PubMed Web of Science ®Google Scholar
• Thorpe CT, Chaudhry S, Lei II, Varone A, Riley GP, Birch HL, Clegg PD, Screen HRC. Tendon overload results in alterations in cell shape and increased markers of inflammation and matrix degradation. Scand J Med Sci Sports. 2015;25(4):e381–391.
   PubMed Web of Science ®Google Scholar
• Spiesz EM, Thorpe CT, Chaudhry S, Riley GP, Birch HL, Clegg PD, Screen HRC. Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise. J Orthop Res. 2015;33(6):889–897. doi:10.1002/jor.22879.
   PubMed Web of Science ®Google Scholar
• Legerlotz K, Jones GC, Screen HRC, Riley GP. Cyclic loading of tendon fascicles using a novel fatigue loading system increases interleukin-6 expression by tenocytes. Scand J Med Sci Sports. 2013;23(1):31–37. doi:10.1111/sms.2013.23.issue-1.
   PubMed Web of Science ®Google Scholar
• Legerlotz K, Jones ER, Screen HRC, Riley GP. Increased expression of IL-6 family members in tendon pathology. Rheumatology (Oxford). 2012;51(7):1161–1165. doi:10.1093/rheumatology/kes002.
   PubMed Web of Science ®Google Scholar
• Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum. 2006;54(3):832–842. doi:10.1002/(ISSN)1529-0131.
   PubMed Web of Science ®Google Scholar
• Hannafin JA, Arnoczky SP, Hoonjan A, Torzilli PA. Effect of stress deprivation and cyclic tensile loading on the material and morphologic properties of canine flexor digitorum profundus tendon: an in vitro study. J Orthop Res. 1995;13(6):907–914. doi:10.1002/(ISSN)1554-527X.
   PubMed Web of Science ®Google Scholar
• Gardner K, Arnoczky SP, Caballero O, Lavagnino M. The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: an in vitro experimental study. Disabil Rehabil. 2008;30(20–22):1523–1529. doi:10.1080/09638280701785395.
   PubMed Web of Science ®Google Scholar
• Thornton GM, Shao X, Chung M, Sciore P, Boorman RS, Hart DA, Lo IKY. Changes in mechanical loading lead to tendonspecific alterations in MMP and TIMP expression: influence of stress deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons. Br J Sports Med. 2010;44(10):698–703. doi:10.1136/bjsm.2008.050575.
   PubMed Web of Science ®Google Scholar
• Wunderli S, Blache U, Piccoli AB, Niederoest B, Holenstein CN, Passini F, Silvan U, Bundgaard L, Auf Dem Keller U, Snedeker JG. Tendon response to matrix unloading is determined by the patho-physiological niche. Matrix Biol. 2019. doi:10.1016/j.matbio.2019.12.003.
   Google Scholar
• Shepherd JH, Riley GP, Screen HR. Early stage fatigue damage occurs in bovine tendon fascicles in the absence of changes in mechanics at either the gross or micro-structural level. J Mech Behav Biomed Mater. 2014;38:163–172. doi:10.1016/j.jmbbm.2014.06.005.
   PubMed Web of Science ®Google Scholar
• Rigby BJ, Hirai N, Spikes JD, Eyring H. The mechanical properties of rat tail tendon. J Gen Physiol. 1959;43(2):265–283. doi:10.1085/jgp.43.2.265.
   PubMed Web of Science ®Google Scholar
• Robinson PS, Lin TW, Jawad AF, Iozzo RV, Soslowsky LJ. Investigating tendon fascicle structure–function relationships in a transgenic-age mouse model using multiple regression models. Ann Biomed Eng. 2004;32(7):924–931. doi:10.1023/B:ABME.0000032455.78459.56.
   PubMed Web of Science ®Google Scholar
• Fessel G, Snedeker JG. Equivalent stiffness after glycosaminoglycan depletion in tendon — an ultra-structural finite element model and corresponding experiments. J Theor Biol. 2011;268(1):77–83. doi:10.1016/j.jtbi.2010.10.007.
   PubMed Web of Science ®Google Scholar
• Arnoczky S, Tian T, Lavagnino M, Gardner K. Ex vivo static tensile loading inhibits MMP-1 expression in rat tail tendon cells through a cytoskeletally based mechanotransduction mechanism. J Orthop Res. 2004;22(2):328–333. doi:10.1016/S0736-0266(03)00185-2.
   PubMed Web of Science ®Google Scholar
• Lavagnino M, Arnoczky SP, Egerbacher M, Gardner KL, Burns ME. Isolated fibrillar damage in tendons stimulates local collagenase mRNA expression and protein synthesis. J Biomech. 2006;39(13):2355–2362. doi:10.1016/j.jbiomech.2005.08.008.
   PubMed Web of Science ®Google Scholar
• Stauber T, Blache U, Snedeker JG. Tendon tissue microdamage and the limits of intrinsic repair. Matrix Biol. 2019. doi:10.1016/j.matbio.2019.07.008.
   PubMed Web of Science ®Google Scholar
• Lavagnino M, Brooks AE, Oslapas AN, Gardner KL, Arnoczky SP. Crimp length decreases in lax tendons due to cytoskeletal tension, but is restored with tensional homeostasis. J Orthop Res. 2017;35(3):573–579. doi:10.1002/jor.v35.3.
   PubMed Web of Science ®Google Scholar
• Gardner K, Lavagnino M, Egerbacher M, Arnoczky SP. Re-establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin-mediated cellular contraction of the extracellular matrix. J Orthop Res. 2012;30(11):1695–1701. doi:10.1002/jor.v30.11.
   PubMed Web of Science ®Google Scholar
• Lavagnino M, Arnoczky SP, Gardner K. In situ deflection of tendon cell-cilia in response to tensile loading: an in vitro study. J Orthop Res. 2011;29(6):925–930. doi:10.1002/jor.v29.6.
   PubMed Web of Science ®Google Scholar
• Jafari L, Savard M, Gobeil F, Langelier E. Characterization of moderate tendinopathy in ex vivo stress-deprived rat tail tendons. Biomed Eng Online. 2019;18(1):54. doi:10.1186/s12938-019-0673-y.
   PubMed Web of Science ®Google Scholar
• Cousineau-Pelletier P, Langelier E. Relative contributions of mechanical degradation, enzymatic degradation, and repair of the extracellular matrix on the response of tendons when subjected to under- and over- mechanical stimulations in vitro. J Orthop Res. 2010;28(2):204–210. doi:10.1002/jor.20982.
   PubMed Web of Science ®Google Scholar
• Choi R, Smith M, Clarke E, Little C. Cellular, matrix, and mechano-biological differences in load-bearing versus positional tendons throughout development and aging: a narrative review. Connect Tissue Res. 2018;59(5):483–494. doi:10.1080/03008207.2018.1504929.
   Web of Science ®Google Scholar
• Maganaris CN, Paul JP. In vivo human tendon mechanical properties. J Physiol. 1999;521(1):307–313. doi:10.1111/tjp.1999.521.issue-1.
   PubMed Web of Science ®Google Scholar
• Wren TA, Yerby SA, BeauprÈ GS, Carter DR. Mechanical properties of the human achilles tendon. Clin Biomech. 2001;16(3):245–251. doi:10.1016/S0268-0033(00)00089-9.
   PubMed Web of Science ®Google Scholar
• Arble JR, Lalley AL, Dyment NA, Joshi P, Shin D-G, Gooch C, Grawe B, Rowe D, Shearn JT. The LG/J murine strain exhibits near-normal tendon biomechanical properties following a full-length central patellar tendon defect. Connect Tissue Res. 2016;57(6):496–506. doi:10.1080/03008207.2016.1213247.
   PubMed Web of Science ®Google Scholar
• Heinemeier KM, Schjerling P, Heinemeier J, Magnusson SP, Kjaer M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C. FASEB J. 2013;27(5):2074–2079. doi:10.1096/fj.12-225599.
   PubMed Web of Science ®Google Scholar
• Heinemeier KM, Schjerling P, Øhlenschlæger TF, Eismark C, Olsen J, Kjær M. Carbon-14 bomb pulse dating shows that tendinopathy is preceded by years of abnormally high collagen turnover. FASEB J. 2018;32(9):4763–4775. doi:10.1096/fj.201701569R.
   PubMed Web of Science ®Google Scholar
• Grinstein M, Dingwall HL, O’Connor LD, Zou K, Capellini TD, Galloway JL. A distinct transition from cell growth to physiological homeostasis in the tendon. eLife. 2019;8:e48689. doi:10.7554/eLife.48689.
   PubMed Web of Science ®Google Scholar
• Arnoczky SP, Lavagnino M, Egerbacher M, Caballero O, Gardner K. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med. 2007;35(5):763–769. doi:10.1177/0363546506296043.
   PubMed Web of Science ®Google Scholar
• Garner W, McDonald JA, Kuhn C, Weeks PM. Autonomous healing of chicken flexor tendons in vitro. J Hand Surg Am. 1988;13(5):697–700. doi:10.1016/S0363-5023(88)80127-8.
   PubMed Web of Science ®Google Scholar
• Abrahamsson S-O, Lundborg G, Lohmander LS. Tendon healing in vivo: an experimental model. Scand J Plast Reconstr Surg. 1989;23(3):199–205. doi:10.3109/02844318909075118.
   Web of Science ®Google Scholar
• Screen HR, Shelton JC, Bader DL, Lee DA. Cyclic tensile strain upregulates collagen synthesis in isolated tendon fascicles. Biochem Biophys Res Commun. 2005;336(2):424–429. doi:10.1016/j.bbrc.2005.08.102.
   PubMed Web of Science ®Google Scholar
• Usmani S, Aurand ER, Medelin M, Fabbro A, Scaini D, Laishram J, Rosselli FB, Ansuini A, Zoccolan D, Scarselli M, De Crescenzi M, Bosi S, Prato M, Ballerini L. 3D meshes of carbon nanotubes guide functional reconnection of segregated spinal explants. Sci Adv. 2016;2(7):e1600087. doi:10.1126/sciadv.1600087.
   PubMed Web of Science ®Google Scholar
• Imler SM, Doshi AN, Levenston ME. Combined effects of growth factors and static mechanical compression on meniscus explant biosynthesis. Osteoarthritis Cartilage. 2004;12(9):736–744. doi:10.1016/j.joca.2004.05.007.
   PubMed Web of Science ®Google Scholar
• Wang X, Zhang J, Li G, Sai N, Han J, Hou Z, Kachelmeier A, Shi X. Vascular regeneration in adult mouse cochlea stimulated by VEGF-A165 and driven by NG2-derived cells ex vivo. Hear Res. 2019;377:179–188. doi:10.1016/j.heares.2019.03.010.
   PubMed Web of Science ®Google Scholar
• Maeda T, Sakabe T, Sunaga A, Sakai K, Rivera AL, Keene DR, Sasaki T, Stavnezer E, Iannotti J, Schweitzer R, Ilic D. Conversion of mechanical force into TGF-beta-mediated biochemical signals. Curr Biol. 2011;21(11):933–941. doi:10.1016/j.cub.2011.04.007.
   PubMed Web of Science ®Google Scholar
• Lavagnino M, Arnoczky SP, Tian T, Vaupel Z. Effect of amplitude and frequency of cyclic tensile strain on the inhibition of MMP-1 mRNA expression in tendon cells: an in vitro study. Connect Tissue Res. 2003;44(3–4):181–187. doi:10.1080/03008200390215881.
   PubMed Web of Science ®Google Scholar
• Spiesz EM, Thorpe CT, Thurner PJ, Screen HR. Structure and collagen crimp patterns of functionally distinct equine tendons, revealed by quantitative polarised light microscopy (qPLM). Acta Biomater. 2018;70:281–292. doi:10.1016/j.actbio.2018.01.034.
   PubMed Web of Science ®Google Scholar
• Shepherd JH, Legerlotz K, Demirci T, Klemt C, Riley GP, Screen HR. Functionally distinct tendon fascicles exhibit different creep and stress relaxation behaviour. Proc Inst Mech Eng H. 2014;228(1):49–59. doi:10.1177/0954411913509977.
   PubMed Web of Science ®Google Scholar
• Lavagnino M, Brooks AE, Oslapas AN, Gardner KL, Arnoczky SP. Crimp length decreases in lax tendons due to cytoskeletal tension, but is restored with tensional homeostasis. J Orthop Res. 2017;35(3):573–579. doi:10.1002/jor.23489.
   PubMed Web of Science ®Google Scholar
• Camp RJ, Liles M, Beale J, Saeidi N, Flynn BP, Moore E, Murthy SK, Ruberti JW. Molecular mechanochemistry: low force switch slows enzymatic cleavage of human type I collagen monomer. J Am Chem Soc. 2011;133(11):4073–4078. doi:10.1021/ja110098b.
   PubMed Web of Science ®Google Scholar
• Ruberti JW, Hallab NJ. Strain-controlled enzymatic cleavage of collagen in loaded matrix. Biochem Biophys Res Commun. 2005;336(2):483–489. doi:10.1016/j.bbrc.2005.08.128.
   PubMed Web of Science ®Google Scholar
• Saini K, Cho S, Dooling LJ, Discher DE. Tension in fibrils suppresses their enzymatic degradation - A molecular mechanism for ‘use it or lose it’. Matrix Biol. 2019. doi:10.1016/j.matbio.2019.06.001.
   PubMed Web of Science ®Google Scholar
• Carreau A, Hafny-Rahbi BE, Matejuk A, Grillon C, Kieda C. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med. 2011;15(6):1239–1253. doi:10.1111/jcmm.2011.15.issue-6.
   PubMed Web of Science ®Google Scholar
• Kubo K, Ikebukuro T, Tsunoda N, Kanehisa H. Noninvasive measures of blood volume and oxygen saturation of human Achilles tendon by red laser lights. Acta Physiol (Oxf). 2008;193(3):257–264. doi:10.1111/j.1748-1716.2008.01841.x.
   PubMed Web of Science ®Google Scholar
• Avery N, Bailey A. Restraining cross-links responsible for the mechanical properties of collagen fibers: natural and artificial. In: Fratzl P, editor. Collagen. Boston (MA): Springer; 2008. p. 81–110.
   Google Scholar
• Makris EA, Responte DJ, Paschos NK, Hu JC, Athanasiou KA. Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking. Proc Natl Acad Sci U S A. 2014;111(45):E4832–41. doi:10.1073/pnas.1414271111.
   PubMed Web of Science ®Google Scholar