Abstract
The management of rotator cuff tears continues to prove challenging for orthopaedic surgeons. Such tears affect most age groups and can lead to significant morbidity in patients. The aetiology of these tears is likely to be multifactorial; however, an understanding of the mechanisms involved is still under review. Despite advancements in surgical operative techniques and the materials used, post-operative recurrence rates after surgical repair remain high. A growing area of research surrounds biological adjuncts used to improve the healing potential of the repaired tissues. This review of recent publications focuses on the strengths and limitations of using stem cells and growth factors in rotator cuff repair.
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References
Gomoll AH, Katz JN, Warner JJP, Millett PJ (2004) Rotator cuff disorders: recognition and management among patients with shoulder pain. Arthritis Rheum 50(12):3751–3761
Meislin RJ, Sperling JW, Stitik TP (2005) Persistent shoulder pain: epidemiology, pathophysiology, and diagnosis. Am J Orthop 34(12 Suppl):5–9
Klatte Schulz F, Pauly S, Scheibel M, Greiner S, Gerhardt C, Hartwig J et al (2013) Characteristics and stimulation potential with BMP-2 and BMP-7 of tenocyte-like cells isolated from the rotator cuff of female donors. PLoS ONE 8(6):e67209
Baumgarten KM, Gerlach D, Galatz LM, Teefey SA, Middleton WD, Ditsios K et al (2010) Cigarette smoking increases the risk for rotator cuff tears. Clin Orthop Relat Res 468(6):1534–1541
Cross JA, Cole BJ, Spatny KP, Sundman E, Romeo AA, Nicholson GP et al (2015) Leukocyte-reduced platelet-rich plasma normalizes matrix metabolism in torn human rotator cuff tendons. Am J Sports Med 43(12):2898–2906
Hoppe S, Alini M, Benneker LM, Milz S, Boileau P, Zumstein MA (2013) Tenocytes of chronic rotator cuff tendon tears can be stimulated by platelet-released growth factors. J Shoulder Elb Surg 22(3):340–349
Jo CH, Shin JS, Park IW, Kim H, Lee SY (2013) Multiple channeling improves the structural integrity of rotator cuff repair. Am J Sports Med 41(11):2650–2657
Beck J, Evans D, Tonino PM, Yong S, Callaci JJ (2012) The biomechanical and histologic effects of platelet-rich plasma on rat rotator cuff repairs. Am J Sports Med 40(9):2037–2044
Dolkart O, Chechik O, Zarfati Y, Brosh T, Alhajajra F, Maman E (2014) A single dose of platelet-rich plasma improves the organization and strength of a surgically repaired rotator cuff tendon in rats. Arch Orthop Trauma Surg 134(9):1271–1277
Ersen A, Demirhan M, Atalar AC, Kapicioğlu M, Baysal G (2014) Platelet-rich plasma for enhancing surgical rotator cuff repair: evaluation and comparison of two application methods in a rat model. Arch Orthop Trauma Surg 134(3):405–411
Wu Y, Dong Y, Chen S, Li Y (2014) Effect of platelet-rich plasma and bioactive glass powder for the improvement of rotator cuff tendon-to-bone healing in a rabbit model. Int J Mol Sci 15:21980–21991
Chung SW, Song BW, Kim YH, Park KU, Oh JH (2013) Effect of platelet-rich plasma and porcine dermal collagen graft augmentation for rotator cuff healing in a rabbit model. Am J Sports Med 41(12):2909–2918
Bergeson AG, Tashjian RZ, Greis PE, Crim J, Stoddard GJ, Burks RT (2012) Effects of platelet-rich fibrin matrix on repair integrity of at-risk rotator cuff tears. Am J Sports Med 40(2):286–293
Castricini R, Longo UG, De Benedetto M, Panfoli N, Pirani P, Zini R, Maffulli N, Denaro V (2011) Platelet-rich plasma augmentation for arthroscopic rotator cuff repair: a randomized controlled trial. Am J Sports Med 39(2):258–265
Zumstein MA, Rumian A, Thélu CÉ, Lesbats V, O’Shea K, Schaer M et al (2016) SECEC Research Grant 2008 II: use of platelet- and leucocyte-rich fibrin (L-PRF) does not affect late rotator cuff tendon healing: a prospective randomized controlled study. J Shoulder Elb Surg 25(1):2–11
Hurley ET, Daren LF, Moran CJ, Mullett H (2018) The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials. Am J Sports Med. p 363546517751397. https://doi.org/10.1177/0363546517751397
Lipner J, Shen H, Cavinatto L, Liu W, Havlioglu N, Xia Y et al (2015) In vivo evaluation of adipose-derived stromal cells delivered with a nanofiber scaffold for tendon-to-bone repair. Tissue Eng Part A 21(21–22):2766–2774
Pauly S, Klatte F, Strobel C, Schmidmaier G, Greiner S, Scheibel M et al (2012) BMP-2 and BMP-7 affect human rotator cuff tendon cells in vitro. J Shoulder Elb Surg 21(4):464–473
Morihara T, Kabuto Y, Sukenari T, Kida Y, Oda R, Arai Y et al (2015) Stimulation of rotator cuff repair by sustained release of bone morphogenetic protein-7 using a gelatin hydrogel sheet. Tissue Eng Part A 21(13–14):2025–2033
Kim HM, Galatz LM, Das R, Havlioglu N, Rothermich SY, Thomopoulos S (2011) The role of transforming growth factor beta isoforms in tendon-to-bone healing. Connect Tissue Res 52(2):87–98
Kovacevic D, Fox AJ, Bedi A, Ying L, Deng XH, Warren RF et al (2011) Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair. Am J Sports Med 39(4):811–819
Manning CN, Kim HM, Sakiyama-Elbert S, Galatz LM, Havlioglu N, Thomopoulos S (2011) Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model. J Orthop Res 29(7):1099–1105
Hee CK, Dines JS, Dines DM, Roden CM, Wisner-Lynch LA, Turner AS et al (2011) Augmentation of a rotator cuff suture repair using rhPDGF-BB and a type I bovine collagen matrix in an ovine model. Am J Sports Med 39(8):1630–1639
Uggen C, Dines J, McGarry M, Grande D, Lee T, Limpisvasti O (2010) The effect of recombinant human platelet-derived growth factor BB-coated sutures on rotator cuff healing in a sheep model. Arthroscopy 26(11):1456–1462
Ide J, Kikukawa K, Hirose J, Iyama K-I, Sakamoto H, Mizuta H (2009) The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts. Arthroscopy: J Arthrosc Relat Surg 25(6):608–616
Peterson DR, Ohashi KL, Aberman HM, Piza PA, Crockett HC, Fernandez JI et al (2015) Evaluation of a collagen-coated, resorbable fiber scaffold loaded with a peptide basic fibroblast growth factor mimetic in a sheep model of rotator cuff repair. J Shoulder Elb Surg 24(11):1764–1773
Zhao S, Zhao J, Dong S, Huangfu X, Li Bin, Yang H et al (2014) Biological augmentation of rotator cuff repair using bFGF-loaded electrospun poly(lactide-co-glycolide) fibrous membranes. Int J Nanomed 9:2373–2385
Ross D, Maerz T, Kurdziel M, Hein J, Doshi S, Bedi A et al (2015) The effect of granulocyte-colony stimulating factor on rotator cuff healing after injury and repair. Clin Orthop Relat Res 473(5):1655–1664
Buchmann S, Sandmann GH, Walz L, Hoppe H, Beitzel K, Wexel G et al (2013) Refixation of the supraspinatus tendon in a rat model—influence of continuous growth factor application on tendon structure. J Orthop Res 31(2):300–305
Tao X, Liu J, Chen L, Zhou Y, Tang K (2015) EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair. Cell Physiol Biochem 35(2):699–709
Murray DH, Kubiak EN, Jazrawi LM, Araghi A, Kummer F, Loebenberg MI et al (2007) The effect of cartilage-derived morphogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. J Shoulder Elb Surg 16(2):251–254
Gulotta LV, Kovacevic D, Cordasco F, Rodeo SA (2011) Evaluation of tumor necrosis factor α blockade on early tendon-to-bone healing in a rat rotator cuff repair model. Arthroscopy: J Arthrosc Relat Surg 27(10):1351–1357
Cheng B, Ge H, Zhou J, Zhang Q (2014) TSG-6 mediates the effect of tendon derived stem cells for rotator cuff healing. Eur Rev Med Pharmacol Sci 18:247–251
MacLean S, Khan WS, Malik AA, Snow M, Anand S (2011) Tendon regeneration and repair with stem cells. Stem Cells Int 2012(4):1–6
Pelinkovic D, Lee JY, Engelhardt M, Rodosky M, Cummins J, Fu FH et al (2004) Muscle cell-mediated gene delivery to the rotator cuff. Tissue Eng 9(1):143–151
Meyer GA, Gibbons MC, Sato E, Lane JG, Ward SR, Engler AJ (2015) Epimuscular fat in the human rotator cuff is a novel beige depot. Stem Cells Transl Med 4(7):764–774
Meyer GA, Farris AL, Sato E, Gibbons M, Lane JG, Ward SR et al (2015) Muscle progenitor cell regenerative capacity in the torn rotator cuff. J Orthop Res 33(3):421–429
Chen H-S, Su Y-T, Chan T-M, Su Y-J, Syu W-S, Harn H-J et al (2015) Human adipose-derived stem cells accelerate the restoration of tensile strength of tendon and alleviate the progression of rotator cuff injury in a rat model. Cell Transpl 24(3):509–520
Mora MV, Antuña SA, Arranz MG, Carrascal MT, Barco R (2014) Application of adipose tissue-derived stem cells in a rat rotator cuff repair model. Injury 45:S22–S27
Kim SH, Chung SW, Oh JH (2014) Expression of insulin-like growth factor type 1 receptor and myosin heavy chain in rabbit’s rotator cuff muscle after injection of adipose-derived stem cell. Knee Surg Sports Traumatol Arthrosc 22(11):2867–2873
Park GY, Kwon DR, Lee SC (2015) Regeneration of Full-Thickness Rotator Cuff Tendon Tear After Ultrasound-Guided Injection With Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a rabbit model. Stem Cells Transl Med 4:1344–1351
Gumucio JP, Flood MD, Roche SM, Sugg KB, Momoh AO, Kosnik PE et al (2015) Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear. Int Orthop 40(4):759–764
Funakoshi T, Spector M (2010) Chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells. J Orthop Res 28(6):716–725
Song N, Armstrong D, Li F, Ouyang H, Niyibizi C (2013) Multipotent mesenchymal stem cells from human subacromial bursa: potential for cell based tendon tissue engineering. Tissue Eng Part A 20(1–2):239–249
Steinert AF, Kunz M, Prager P, Göbel S, Klein-Hitpass L, Ebert R et al (2015) Characterization of bursa subacromialis-derived mesenchymal stem cells. Stem Cell Res Ther 6(1):1–14
Utsunomiya H, Uchida S, Sekiya I, Sakai A, Moridera K, Nakamura T (2013) Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears. Am J Sports Med 41(3):0363546512473269–0363546512473668
Randelli P, Conforti E, Piccoli M, Ragone V, Creo P, Cirillo F et al (2013) Isolation and characterization of 2 new human rotator cuff and long head of biceps tendon cells possessing stem cell-like self-renewal and multipotential differentiation capacity. Am J Sports Med 41(7):1653–1664
Tsai C-C, Huang T-F, Ma H-L, Chiang E-R, Hung S-C (2013) Isolation of mesenchymal stem cells from shoulder rotator cuff: a potential source for muscle and tendon repair. Cell Transpl 22(3):413–422
Sundar S, Pendegrass CJ, Blunn GW (2009) Tendon bone healing can be enhanced by demineralized bone matrix: a functional and histological study. J Biomed Mater Res B Appl Biomater 88B(1):115–122
Chang C-H, Chen C-H, Su C-Y, Liu H-T, Yu C-M (2009) Rotator cuff repair with periosteum for enhancing tendon-bone healing: a biomechanical and histological study in rabbits. Knee Surg Sports Traumatol Arthrosc 17(12):1447–1453
Durant TJS, Dyment N, McCarthy MBR, Cote MP, Arciero RA, Mazzocca AD et al (2014) Mesenchymal stem cell response to growth factor treatment and low oxygen tension in 3-dimensional construct environment. Muscles Ligaments Tendons J 4(1):46–51
Hernigou P, Merouse G, Duffiet P, Chevalier N, Rouard H (2015) Reduced levels of mesenchymal stem cells at the tendon-bone interface tuberosity in patients with symptomatic rotator cuff tear. Int Orthop 39(6):1219–1225
Mazzocca AD, McCarthy MBR, Chowaniec DM, Cote MP, Arciero RA, Drissi H (2010) Rapid isolation of human stem cells (connective tissue progenitor cells) from the proximal humerus during arthroscopic rotator cuff surgery. Am J Sports Med 38(7):1438–1447
Kida Y, Morihara T, Matsuda K-I, Kajikawa Y, Tachiiri H, Iwata Y et al (2013) Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff. J Shoulder Elb Surg 22(2):197–205
Levy DM, Saifi C, Perri JL, Zhang R, Gardner TR, Ahmad CS (2013) Rotator cuff repair augmentation with local autogenous bone marrow via humeral cannulation in a rat model. J Shoulder Elb Surg 22(9):1256–1264
Gulotta LV, Kovacevic D, Montgomery S, Ehteshami JR, Packer JD, Rodeo SA (2010) Stem cells genetically modified with the developmental gene MT1-MMP improve regeneration of the supraspinatus tendon-to-bone insertion site. Am J Sports Med 38(7):1429–1437
Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA (2011) Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med 39(6):1282–1289
Loeffler BJ, Scannell BP, Peindl RD, Connor P, Davis DE, Hoelscher GL et al (2013) Cell-based tissue engineering augments tendon-to-bone healing in a rat supraspinatus model. J Orthop Res 31(3):407–412
Tornero-Esteban P, Hoyas JA, Villafuertes E, Rodríguez-Bobada C, López-Gordillo Y, Rojo FJ et al (2015) Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold. J Orthop Surg Res 10(1):1
Omi R, Gingery A, Steinmann SP, Amadio PC, An K-N, Zhao C (2016) Rotator cuff repair augmentation in a rat model that combines a multilayer xenograft tendon scaffold with bone marrow stromal cells. J Shoulder Elb Surg 25(3):469–477
Kim Y-S, Lee H-J, Ok J-H, Park J-S, Kim D-W (2013) Survivorship of implanted bone marrow-derived mesenchymal stem cells in acute rotator cuff tear. J Shoulder Elb Surg 22(8):1037–1045
Gomes JLE, da Silva RC, Silla LMR, Abreu MR, Pellanda R (2012) Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells. Knee Surg Sports Traumatol Arthrosc 20(2):373–377
Hernigou P, Lachaniette CHF, Delambre J, Zilber S, Duffiet P, Chevallier N et al (2014) Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop 38(9):1811–1818
Taniguchi N, Suenaga N, Oizumi N, Miyoshi N, Yamaguchi H, Inoue K et al (2015) Bone marrow stimulation at the footprint of arthroscopic surface-holding repair advances cuff repair integrity. J Shoulder Elb Surg 24(6):860–866
Grambart ST (2015) Sports medicine and platelet-rich plasma. Clin Podiatr Med Surg 32(1):99–107
Moraes VY, Lenza M, Tamaoki MJ (2014) Platelet-rich therapies for musculoskeletal soft tissue injuries. Database Syst Rev 12:CD010071
Cai Y-Z, Zhang C, Lin X-J (2015) Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis. J Shoulder Elb Surg 24(12):1852–1859
Ahmad Z, Wardale J, Brooks R, Henson F, Noorani A, Rushton N (2012) Exploring the application of stem cells in tendon repair and regeneration. Arthroscopy: J Arthrosc Relat Surg 28(7):1018–1029
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Tsekes, D., Konstantopoulos, G., Khan, W.S. et al. Use of stem cells and growth factors in rotator cuff tendon repair. Eur J Orthop Surg Traumatol 29, 747–757 (2019). https://doi.org/10.1007/s00590-019-02366-x
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DOI: https://doi.org/10.1007/s00590-019-02366-x