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Physiology and Homeostasis of Musculoskeletal Structures, Injury Response, Healing Process, and Regenerative Medicine Approaches

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Bio-orthopaedics

Abstract

Kaitlyn E. Whitney, Ioanna K. Bolia, Jorge Chahla, Hajime Utsunomiya, Thos A. Evans, Matthew Provencher, Peter J. MilletThe Steadman Clinic and Steadman Philippon Research Institute, Vail, CO, USAJohnny HuardThe Steadman Clinic and Steadman Philippon Research Institute, Vail, CO, USADepartment of Orthopedic Surgery, University of Texas Health Science Center at Houston, Houston, Texas, USA

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References

  1. Hoffmann A, Gross G. Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene-therapeutic approaches. Int Orthop. 2007;31(6):791–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Almekinders LC, Temple JD. Etiology, diagnosis, and treatment of tendonitis: an analysis of the literature. Med Sci Sports Exerc. 1998;30(8):1183–90.

    Article  CAS  PubMed  Google Scholar 

  3. Matava MJ. Patellar tendon ruptures. J Am Acad Orthop Surg. 1996;4(6):287–96.

    Article  CAS  PubMed  Google Scholar 

  4. Vilaboa N, Voellmy R. Regulatable gene expression systems for gene therapy. Curr Gene Ther. 2006;6(4):421–38.

    Article  CAS  PubMed  Google Scholar 

  5. Xu Y, Murrell GA. The basic science of tendinopathy. Clin Orthop Relat Res. 2008;466(7):1528–38.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hoffmann A, Gross G. Tendon and ligament engineering: from cell biology to in vivo application. Regen Med. 2006;1(4):563–74.

    Article  CAS  PubMed  Google Scholar 

  7. Hunziker EB, Rosenberg LC. Repair of partial-thickness defects in articular cartilage: cell recruitment from the synovial membrane. J Bone Joint Surg Am. 1996;78(5):721–33.

    Article  CAS  PubMed  Google Scholar 

  8. Maffulli N, Moller HD, Evans CH. Tendon healing: can it be optimised? Br J Sports Med. 2002;36(5):315–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gage BE, et al. Epidemiology of 6.6 million knee injuries presenting to United States emergency departments from 1999 through 2008. Acad Emerg Med. 2012;19(4):378–85.

    Article  PubMed  Google Scholar 

  10. Farrokhi S, et al. Altered tibiofemoral joint contact mechanics and kinematics in patients with knee osteoarthritis and episodic complaints of joint instability. Clin Biomech (Bristol, Avon). 2014;29(6):629–35.

    Article  Google Scholar 

  11. Miyamoto RG, Bosco JA, Sherman OH. Treatment of medial collateral ligament injuries. J Am Acad Orthop Surg. 2009;17(3):152–61.

    Article  PubMed  Google Scholar 

  12. Bhargava MM, et al. The effect of cytokines on the proliferation and migration of bovine meniscal cells. Am J Sports Med. 1999;27(5):636–43.

    CAS  PubMed  Google Scholar 

  13. Niyibizi C, et al. Type V collagen is increased during rabbit medial collateral ligament healing. Knee Surg Sports Traumatol Arthrosc. 2000;8(5):281–5.

    Article  CAS  PubMed  Google Scholar 

  14. Frank C, Amiel D, Akeson WH. Healing of the medial collateral ligament of the knee. A morphological and biochemical assessment in rabbits. Acta Orthop Scand. 1983;54(6):917–23.

    Article  CAS  PubMed  Google Scholar 

  15. Knapik DM, et al. Mechanosignaling in bone health, trauma and inflammation. Antioxid Redox Signal. 2014;20(6):970–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sims NA, Vrahnas C. Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts. Arch Biochem Biophys. 2014;561:22–8.

    Article  CAS  PubMed  Google Scholar 

  17. Regan J, Long F. Notch signaling and bone remodeling. Curr Osteoporos Rep. 2013;11(2):126–9.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Canalis E, et al. Notch signaling in osteocytes differentially regulates cancellous and cortical bone remodeling. J Biol Chem. 2013;288(35):25614–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zanotti S, Canalis E. Notch signaling in skeletal health and disease. Eur J Endocrinol. 2013;168(6):R95–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hojo H, Ohba S, Chung U-i. Signaling pathways regulating the specification and differentiation of the osteoblast lineage. Regen Ther. 2015;1:57–62.

    Article  Google Scholar 

  21. Wu M, Chen G, Li YP. TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pickarski M, et al. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord. 2011;12:197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Buckland-Wright JC, MacFarlane DG, Lynch JA. Relationship between joint space width and subchondral sclerosis in the osteoarthritic hand: a quantitative microfocal radiographic study. J Rheumatol. 1992;19(5):788–95.

    CAS  PubMed  Google Scholar 

  24. Firth EC. The response of bone, articular cartilage and tendon to exercise in the horse. J Anat. 2006;208(4):513–26.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Burr DB. The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998;10(3):256–62.

    Article  CAS  PubMed  Google Scholar 

  26. Marijnissen AC, et al. Ankle images digital analysis (AIDA): digital measurement of joint space width and subchondral sclerosis on standard radiographs. Osteoarthritis Cartil. 2001;9(3):264–72.

    Article  CAS  Google Scholar 

  27. Crema MD, et al. The relationship between subchondral sclerosis detected with MRI and cartilage loss in a cohort of subjects with knee pain: the knee osteoarthritis progression (KOAP) study. Osteoarthritis Cartil. 2014;22(4):540–6.

    Article  CAS  Google Scholar 

  28. Barr AJ, et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther. 2015;17:228.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Gomoll AH, et al. Triad of cartilage restoration for unicompartmental arthritis treatment in young patients: meniscus allograft transplantation, cartilage repair and osteotomy. J Knee Surg. 2009;22(2):137–41.

    Article  PubMed  Google Scholar 

  30. Zhang, W., et al., VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation. Eur Cell Mater. 2014;27:1–11; discussion 11–2.

    Google Scholar 

  31. Peng H, et al. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest. 2002;110(6):751–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Usas A, et al. Bone regeneration mediated by BMP4-expressing muscle-derived stem cells is affected by delivery system. Tissue Eng Part A. 2009;15(2):285–93.

    Article  CAS  PubMed  Google Scholar 

  33. Huard J, Li Y, Fu FH. Muscle injuries and repair: current trends in research. J Bone Joint Surg Am. 2002;84-A(5):822–32.

    Article  PubMed  Google Scholar 

  34. Gharaibeh B, et al. Biological approaches to improve skeletal muscle healing after injury and disease. Birth Defects Res C Embryo Today. 2012;96(1):82–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bondesen BA, et al. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol Cell Physiol. 2004;287(2):C475–83.

    Article  CAS  PubMed  Google Scholar 

  36. Menetrey J, et al. Growth factors improve muscle healing in vivo. J Bone Joint Surg Br. 2000;82(1):131–7.

    Article  CAS  PubMed  Google Scholar 

  37. Terada S, et al. Use of an antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury. J Bone Joint Surg Am. 2013;95(11):980–8.

    Article  PubMed  Google Scholar 

  38. Bader DL, Salter DM, Chowdhury TT. Biomechanical influence of cartilage homeostasis in health and disease. Arthritis. 2011;2011:979032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Creaby MW, et al. Dynamic knee loading is related to cartilage defects and tibial plateau bone area in medial knee osteoarthritis. Osteoarthritis Cartil. 2010;18(11):1380–5.

    Article  CAS  Google Scholar 

  40. Natoli RM, Scott CC, Athanasiou KA. Temporal effects of impact on articular cartilage cell death, gene expression, matrix biochemistry, and biomechanics. Ann Biomed Eng. 2008;36(5):780–92.

    Article  PubMed  Google Scholar 

  41. Furukawa T, et al. Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee. J Bone Joint Surg Am. 1980;62(1):79–89.

    Article  CAS  PubMed  Google Scholar 

  42. Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1993;75(4):532–53.

    Article  CAS  PubMed  Google Scholar 

  43. Mithoefer K, et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J Bone Joint Surg Am. 2005;87(9):1911–20.

    PubMed  Google Scholar 

  44. Siclari A, et al. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year. Clin Orthop Relat Res. 2012;470(3):910–9.

    Article  PubMed  Google Scholar 

  45. Steadman JR, Rodkey WG, Singleton SB, Briggs KK. Microfracture technique for full-thickness chondral defects: technique and clinical results. Oper Tech Orthop. 1997;7(4):300–4.

    Article  Google Scholar 

  46. Steadman JR, et al. The microfracture technique in the treatment of full-thickness chondral lesions of the knee in National Football League players. J Knee Surg. 2003;16(2):83–6.

    PubMed  Google Scholar 

  47. Steadman JR, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res. 2001;391(Suppl):S362–9.

    Article  Google Scholar 

  48. Frisbie DD, et al. Early events in cartilage repair after subchondral bone microfracture. Clin Orthop Relat Res. 2003;407:215–27.

    Article  Google Scholar 

  49. Steadman JR, et al. Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy. 2003;19(5):477–84.

    Article  PubMed  Google Scholar 

  50. Bedi A, Feeley BT, Williams III RJ. Management of articular cartilage defects of the knee. J Bone Joint Surg Am. 2010;92(4):994–1009.

    Article  PubMed  Google Scholar 

  51. Green CJ, et al. The biology and clinical evidence of microfracture in hip preservation surgery. J Hip Preserv Surg. 2016;3(2):108–23.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Barenius B, et al. Increased risk of osteoarthritis after anterior cruciate ligament reconstruction: a 14-year follow-up study of a randomized controlled trial. Am J Sports Med. 2014;42(5):1049–57.

    Article  PubMed  Google Scholar 

  53. Carter TE, et al. In vivo cartilage strain increases following medial meniscal tear and correlates with synovial fluid matrix metalloproteinase activity. J Biomech. 2015;48(8):1461–8.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wyland DJ, et al. Chondropathy after meniscal tear or partial meniscectomy in a canine model. J Orthop Res. 2002;20(5):996–1002.

    Article  PubMed  Google Scholar 

  55. Petty CA, Lubowitz JH. Does arthroscopic partial meniscectomy result in knee osteoarthritis? A systematic review with a minimum of 8 years’ follow-up. Arthroscopy. 2011;27(3):419–24.

    Article  PubMed  Google Scholar 

  56. Brophy RH, et al. Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear. J Bone Joint Surg Am. 2012;94(5):385–93.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Rongen JJ, et al. Societal and economic effect of meniscus scaffold procedures for irreparable meniscus injuries. Am J Sports Med. 2016;44(7):1724–34.

    Article  PubMed  Google Scholar 

  58. Brandt KD, Dieppe P, Radin EL. Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am. 2008;34(3):531–59.

    Article  PubMed  Google Scholar 

  59. Osawa A, et al. The use of blood vessel-derived stem cells for meniscal regeneration and repair. Med Sci Sports Exerc. 2013;45(5):813–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Freymann U, et al. Effect of human serum and 2 different types of platelet concentrates on human meniscus cell migration, proliferation, and matrix formation. Arthroscopy. 2016;32(6):1106–16.

    Article  PubMed  Google Scholar 

  61. Hennerbichler A, et al. Regional differences in prostaglandin E2 and nitric oxide production in the knee meniscus in response to dynamic compression. Biochem Biophys Res Commun. 2007;358(4):1047–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Webber RJ, et al. An organ culture model for assaying wound repair of the fibrocartilaginous knee joint meniscus. Am J Sports Med. 1989;17(3):393–400.

    Article  CAS  PubMed  Google Scholar 

  63. Arnoczky SP, Warren RF. The microvasculature of the meniscus and its response to injury. An experimental study in the dog. Am J Sports Med. 1983;11(3):131–41.

    Article  CAS  PubMed  Google Scholar 

  64. Abrams GD, et al. Trends in meniscus repair and meniscectomy in the United States, 2005-2011. Am J Sports Med. 2013;41(10):2333–9.

    Article  PubMed  Google Scholar 

  65. Andersson-Molina H, Karlsson H, Rockborn P. Arthroscopic partial and total meniscectomy: a long-term follow-up study with matched controls. Arthroscopy. 2002;18(2):183–9.

    Article  PubMed  Google Scholar 

  66. Ferguson SJ, et al. An in vitro investigation of the acetabular labral seal in hip joint mechanics. J Biomech. 2003;36(2):171–8.

    Article  CAS  PubMed  Google Scholar 

  67. Philippon MJ, et al. The hip fluid seal—part I: the effect of an acetabular labral tear, repair, resection, and reconstruction on hip fluid pressurization. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):722–9.

    Article  PubMed  Google Scholar 

  68. Nepple JJ, et al. The hip fluid seal—part II: the effect of an acetabular labral tear, repair, resection, and reconstruction on hip stability to distraction. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):730–6.

    Article  PubMed  Google Scholar 

  69. Haddad B, Konan S, Haddad FS. Debridement versus re-attachment of acetabular labral tears: a review of the literature and quantitative analysis. Bone Joint J. 2014;96-B(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  70. Philippon MJ, et al. Arthroscopic management of femoroacetabular impingement: osteoplasty technique and literature review. Am J Sports Med. 2007;35(9):1571–80.

    Article  PubMed  Google Scholar 

  71. Ayeni OR, et al. The hip labrum reconstruction: indications and outcomes—a systematic review. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):737–43.

    Article  PubMed  Google Scholar 

  72. Chahla J, et al. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sports Med. 2016;4(1):2325967115625481.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Bauer DC, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartil. 2006;14(8):723–7.

    Article  CAS  Google Scholar 

  74. Ohlendieck K. Proteomic identification of biomarkers of skeletal muscle disorders. Biomark Med. 2013;7(1):169–86.

    Article  CAS  PubMed  Google Scholar 

  75. Barbe MF, Gallagher S, Popoff SN. Serum biomarkers as predictors of stage of work-related musculoskeletal disorders. J Am Acad Orthop Surg. 2013;21(10):644–6.

    Article  PubMed  Google Scholar 

  76. Pruna R, et al. Genetic biomarkers in non-contact muscle injuries in elite soccer players. Knee Surg Sports Traumatol Arthrosc [Internet]. 2016;24(4):1–8. DOI: 10.1007/s00167-016-4081-6 [Cited 2017 Mar 30].

  77. Strecker W, et al. Early biochemical characterization of soft-tissue trauma and fracture trauma. J Trauma. 1999;47(2):358–64.

    Article  CAS  PubMed  Google Scholar 

  78. Bedi A, et al. Elevation in circulating biomarkers of cartilage damage and inflammation in athletes with femoroacetabular impingement. Am J Sports Med. 2013;41(11):2585–90.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Clohisy JC, John LCS, Schutz AL. Surgical treatment of femoroacetabular impingement: a systematic review of the literature. Clin Orthop Relat Res. 2010;468(2):555–64.

    Article  PubMed  Google Scholar 

  80. Hunter DJ, et al. Biomarkers for osteoarthritis: current position and steps towards further validation. Best Pract Res Clin Rheumatol. 2014;28(1):61–71.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Nepple JJ, et al. What is the utility of biomarkers for assessing the pathophysiology of hip osteoarthritis? A systematic review. Clin Orthop Relat Res. 2015;473(5):1683–701.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Trusheim MR, Berndt ER, Douglas FL. Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers. Nat Rev Drug Discov. 2007;6(4):287–93.

    Article  CAS  PubMed  Google Scholar 

  83. Clark AG, et al. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheum. 1999;42(11):2356–64.

    Article  CAS  PubMed  Google Scholar 

  84. Elliott AL, et al. Serum hyaluronan levels and radiographic knee and hip osteoarthritis in African Americans and Caucasians in the Johnston County Osteoarthritis Project. Arthritis Rheum. 2005;52(1):105–11.

    Article  CAS  PubMed  Google Scholar 

  85. Garnero P, et al. Association between spine disc degeneration and type II collagen degradation in postmenopausal women: the OFELY study. Arthritis Rheum. 2004;50(10):3137–44.

    Article  PubMed  Google Scholar 

  86. Kraus VB, et al. Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis. Osteoarthritis Cartil. 2011;19(5):515–42.

    Article  CAS  Google Scholar 

  87. Arden N, et al. Can we identify patients with high risk of osteoarthritis progression who will respond to treatment? A focus on biomarkers and frailty. Drugs Aging. 2015;32(7):525–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Lanzer WL, Komenda G. Changes in articular cartilage after meniscectomy. Clin Orthop Relat Res. 1990;252:41–8.

    Google Scholar 

  89. Tortorella MD, et al. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Science. 1999;284(5420):1664–6.

    Article  CAS  PubMed  Google Scholar 

  90. Tortorella MD, et al. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthritis Cartil. 2001;9(6):539–52.

    Article  CAS  Google Scholar 

  91. Lim SS, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–60.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Prieto-Alhambra D, et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann Rheum Dis. 2014;73(9):1659–64.

    Article  PubMed  Google Scholar 

  93. Abbaszade I, et al. Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family. J Biol Chem. 1999;274(33):23443–50.

    Article  CAS  PubMed  Google Scholar 

  94. Murphy G, et al. Matrix metalloproteinases in arthritic disease. Arthritis Res. 2002;4(Suppl 3):S39–49.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Roach HI, et al. Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum. 2005;52(10):3110–24.

    Article  CAS  PubMed  Google Scholar 

  96. Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001;44(3):585–94.

    Article  CAS  PubMed  Google Scholar 

  97. Wu W, et al. Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. Arthritis Rheum. 2002;46(8):2087–94.

    Article  CAS  PubMed  Google Scholar 

  98. Kapoor M, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42.

    Article  CAS  PubMed  Google Scholar 

  99. Yamanaka S. Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif. 2008;41(Suppl 1):51–6.

    PubMed  Google Scholar 

  100. Aigner T, McKenna L. Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002;59(1):5–18.

    Article  CAS  PubMed  Google Scholar 

  101. Thibault M, Poole AR, Buschmann MD. Cyclic compression of cartilage/bone explants in vitro leads to physical weakening, mechanical breakdown of collagen and release of matrix fragments. J Orthop Res. 2002;20(6):1265–73.

    Article  CAS  PubMed  Google Scholar 

  102. Eyre DR, et al. Recent developments in cartilage research: matrix biology of the collagen II/IX/XI heterofibril network. Biochem Soc Trans. 2002;30(Pt 6):893–9.

    CAS  PubMed  Google Scholar 

  103. Stevens AL, et al. Mechanical injury and cytokines cause loss of cartilage integrity and upregulate proteins associated with catabolism, immunity, inflammation, and repair. Mol Cell Proteomics. 2009;8(7):1475–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115–26.

    Article  PubMed  Google Scholar 

  105. Foster TE, Pusaka BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med. 2009;37(11):2259–72.

    Article  PubMed  Google Scholar 

  106. Italiano Jr JE, et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008;111(3):1227–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sundman EA, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35–41.

    Article  PubMed  Google Scholar 

  108. Osterman C, McCarthy MB, Cote MP, Beitzel K, Bradley J, Polkowski G, Mazzocca AD. Platelet-rich plasma increases anti-inflammatory markers in a human coculture model for osteoarthritis. Am J Sports Med. 2015;43(6):1474–84.

    Article  PubMed  Google Scholar 

  109. Dragoo JL, et al. Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. Am J Sports Med. 2014;42(3):610–8.

    Article  PubMed  Google Scholar 

  110. Cavallo C, et al. Comparison of platelet-rich plasma formulations for cartilage healing: an in vitro study. J Bone Joint Surg Am. 2014;96(5):423–9.

    Article  PubMed  Google Scholar 

  111. Filardo G, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2082–91.

    Article  PubMed  Google Scholar 

  112. Kon E, et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011;27(11):1490–501.

    Article  PubMed  Google Scholar 

  113. Hart R, et al. Allograft alone versus allograft with bone marrow concentrate for the healing of the instrumented posterolateral lumbar fusion. Spine J. 2014;14(7):1318–24.

    Article  PubMed  Google Scholar 

  114. Jungbluth P, et al. The early phase influence of bone marrow concentrate on metaphyseal bone healing. Injury. 2013;44(10):1285–94.

    Article  CAS  PubMed  Google Scholar 

  115. Akcay S, Kazimoglu C. Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res. 2014;472(7):2301–2.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Smyth NA, et al. Establishing proof of concept: platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus. World J Orthod. 2012;3(7):101–8.

    Article  Google Scholar 

  117. Gigante A, et al. Arthroscopic knee cartilage repair with covered microfracture and bone marrow concentrate. Arthrosc Tech. 2012;1(2):e175–80.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Fortier LA, et al. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010;92(10):1927–37.

    Article  PubMed  Google Scholar 

  119. Gobbi A, et al. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up. Cartilage. 2011;2(3):286–99.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Gobbi A, et al. One-step surgery with multipotent stem cells and hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc [Internet]. 2016;24(1):1–8. DOI: 10.1007/s00167-016-3984-6 [Cited 2017 Mar 30].

  121. Kim JD, et al. Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection in degenerative arthritis of the knee. Eur J Orthop Surg Traumatol. 2014;24(8):1505–11.

    Article  PubMed  Google Scholar 

  122. LaPrade RF, et al. Biologic treatments for sports injuries II think tank—current concepts, future research, and barriers to advancement, part 1: biologics overview, ligament injury, tendinopathy. Am J Sports Med. 2016;44(12):3270–3283.

    Google Scholar 

  123. Chu CR. The challenge and the promise of bone marrow cells for human cartilage repair. Cartilage. 2015;6(2 Suppl):36S–45S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Cassano JM, Kennedy JG, Ross KA, Fraser EJ, Goodale MB, Fortier LA. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. Knee Surg Sports Traumatol Arthrosc [Internet]. 2016;24(2):1–10. DOI: 10.1007/s00167-016-3981-9 [Cited 2017 Mar 30].

  125. Indrawattana N, et al. Growth factor combination for chondrogenic induction from human mesenchymal stem cell. Biochem Biophys Res Commun. 2004;320(3):914–9.

    Article  CAS  PubMed  Google Scholar 

  126. Diekman BO, et al. Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng Part A. 2010;16(2):523–33.

    Article  CAS  PubMed  Google Scholar 

  127. Grigolo B, et al. Novel nano-composite biomimetic biomaterial allows chondrogenic and osteogenic differentiation of bone marrow concentrate derived cells. J Mater Sci Mater Med. 2015;26(4):173.

    Article  PubMed  CAS  Google Scholar 

  128. Nejadnik H, et al. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38(6):1110–6.

    Article  PubMed  Google Scholar 

  129. Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol. 2015;11(4):234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Gerich TG, et al. Gene transfer to the rabbit patellar tendon: potential for genetic enhancement of tendon and ligament healing. Gene Ther. 1996;3(12):1089–93.

    CAS  PubMed  Google Scholar 

  131. Hildebrand KA, et al. Early expression of marker genes in the rabbit medial collateral and anterior cruciate ligaments: the use of different viral vectors and the effects of injury. J Orthop Res. 1999;17(1):37–42.

    Article  CAS  PubMed  Google Scholar 

  132. Nakamura N, et al. Early biological effect of in vivo gene transfer of platelet-derived growth factor (PDGF)-B into healing patellar ligament. Gene Ther. 1998;5(9):1165–70.

    Article  CAS  PubMed  Google Scholar 

  133. Bolt P, et al. BMP-14 gene therapy increases tendon tensile strength in a rat model of Achilles tendon injury. J Bone Joint Surg Am. 2007;89(6):1315–20.

    Article  PubMed  Google Scholar 

  134. Huard J, et al. Gene transfer to muscle using herpes simplex virus-based vectors. Neuromuscul Disord. 1997;7(5):299–313.

    Article  CAS  PubMed  Google Scholar 

  135. Huard J, et al. LacZ gene transfer to skeletal muscle using a replication-defective herpes simplex virus type 1 mutant vector. Hum Gene Ther. 1997;8(4):439–52.

    Article  CAS  PubMed  Google Scholar 

  136. Goto H, et al. Gene therapy for meniscal injury: enhanced synthesis of proteoglycan and collagen by meniscal cells transduced with a TGFbeta(1)gene. Osteoarthritis Cartil. 2000;8(4):266–71.

    Article  CAS  Google Scholar 

  137. Goto H, et al. Transfer of lacZ marker gene to the meniscus. J Bone Joint Surg Am. 1999;81(7):918–25.

    Article  CAS  PubMed  Google Scholar 

  138. Yokoo N, et al. Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector. Arthritis Rheum. 2005;52(1):164–70.

    Article  CAS  PubMed  Google Scholar 

  139. Kuroda R, et al. Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum. 2006;54(2):433–42.

    Article  CAS  PubMed  Google Scholar 

  140. McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 2001;8(16):1248–54.

    Article  CAS  PubMed  Google Scholar 

  141. Yu X, et al. How does the pathophysiological context influence delivery of bone growth factors? Adv Drug Deliv Rev. 2015;84:68–84.

    Article  CAS  PubMed  Google Scholar 

  142. Burnouf T, et al. Human platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials. 2016;76:371–87.

    Article  CAS  PubMed  Google Scholar 

  143. Prasad VK, et al. Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant. 2011;17(4):534–41.

    Article  CAS  PubMed  Google Scholar 

  144. Barrilleaux B, et al. Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng. 2006;12(11):3007–19.

    Article  CAS  PubMed  Google Scholar 

  145. Filipczyk A, et al. Network plasticity of pluripotency transcription factors in embryonic stem cells. Nat Cell Biol. 2015;17(10):1235–46.

    Article  CAS  PubMed  Google Scholar 

  146. Girlovanu M, et al. Stem cells—biological update and cell therapy progress. Clujul Med. 2015;88(3):265–71. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632881/.

  147. Kim YS, Choi YJ, Koh YG. Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes. Am J Sports Med. 2015;43(9):2293–301.

    Article  PubMed  Google Scholar 

  148. Kim YS, et al. Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthritis Cartil. 2016;24(2):237–45.

    Article  CAS  Google Scholar 

  149. Samsonraj RM, et al. Establishing criteria for human mesenchymal stem cell potency. Stem Cells. 2015;33(6):1878–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Whitaker MJ, et al. Growth factor release from tissue engineering scaffolds. J Pharm Pharmacol. 2001;53(11):1427–37.

    Article  CAS  PubMed  Google Scholar 

  151. Wei J, et al. The role of cell seeding, bio-scaffolds, and the in-vivo microenvironment in the guided generation of osteochondral composite tissue. Tissue Eng Part A. 2016;22(23-24):1337–1347.

    Google Scholar 

  152. Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv Drug Deliv Rev. 2012;64(12):1292–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Pennesi G, et al. Regulatory influence of scaffolds on cell behavior: how cells decode biomaterials. Curr Pharm Biotechnol. 2011;12(2):151–9.

    Article  CAS  PubMed  Google Scholar 

  154. Beitzel K, et al. US definitions, current use, and FDA stance on use of platelet-rich plasma in sports medicine. J Knee Surg. 2015;28(1):29–34.

    Article  PubMed  Google Scholar 

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Whitney, K.E. et al. (2017). Physiology and Homeostasis of Musculoskeletal Structures, Injury Response, Healing Process, and Regenerative Medicine Approaches. In: Gobbi, A., Espregueira-Mendes, J., Lane, J., Karahan, M. (eds) Bio-orthopaedics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-54181-4_6

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