Top

Clinical Orthopaedics and Related Research®

Published in:

01-03-2008 | Symposium: New Approaches to Shoulder Surgery

Biological Augmentation of Rotator Cuff Tendon Repair

Authors: David Kovacevic, BS, Scott A. Rodeo, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 3/2008

Abstract

A histologically normal insertion site does not regenerate following rotator cuff tendon-to-bone repair, which is likely due to abnormal or insufficient gene expression and/or cell differentiation at the repair site. Techniques to manipulate the biologic events following tendon repair may improve healing. We used a sheep infraspinatus repair model to evaluate the effect of osteoinductive growth factors and BMP-12 on tendon-to-bone healing. Magnetic resonance imaging and histology showed increased formation of new bone and fibrocartilage at the healing tendon attachment site in the treated animals, and biomechanical testing showed improved load-to-failure. Other techniques with potential to augment repair site biology include use of platelets isolated from autologous blood to deliver growth factors to a tendon repair site. Modalities that improve local vascularity, such as pulsed ultrasound, have the potential to augment rotator cuff healing. Important information about the biology of tendon healing can also be gained from studies of substances that inhibit healing, such as nicotine and antiinflammatory medications. Future approaches may include the use of stem cells and transcription factors to induce formation of the native tendon-bone insertion site after rotator cuff repair surgery.

Alvarez CM, Litchfield R, Jackowski D, Griffin S, Kirkley A. A prospective, double-blind, randomized clinical trial comparing subacromial injection of betamethasone and xylocaine to xylocaine alone in chronic rotator cuff tendinosis. Am J Sports Med. 2005;33:255–262.PubMedCrossRef

Asou Y, Nifuji A, Tsuji K, Shinomiya K, Olson EN, Koopman P, Noda M. Coordinated expression of scleraxis and Sox9 genes during embryonic development of tendons and cartilage. J Orthop Res. 2002;20:827–833.PubMedCrossRef

Aspenberg P, Forslund C. Enhanced tendon healing with GDF 5 and 6. Acta Orthop Scand. 1999;70:51–54.PubMed

Aspenberg P, Forslund C. Bone morphogenetic proteins and tendon repair. Scand J Med Sci Sports. 2000;10:372–375.PubMedCrossRef

Balasubramaniam P, Prathap K. The effect of injection of hydrocortisone into rabbit calcaneal tendons. J Bone Joint Surg Br. 1972;54:729–734.PubMed

Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab. 2001;86:5108–5117.PubMedCrossRef

Biberthaler P, Wiedemann E, Nerlich A, Kettler M, Mussack T, Deckelmann S, Mutschler W. Microcirculation associated with degenerative rotator cuff lesions: in vivo assessment with orthogonal polarization spectral imaging during arthroscopy of the shoulder. J Bone Joint Surg Am. 2003;85:475–480.PubMed

Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. 2005;87:1229–1240.PubMedCrossRef

Bray RC, Shrive NG, Frank CB, Chimich DD. The early effects of joint immobilization on medial collateral ligament healing in an ACL-deficient knee: a gross anatomic and biomechanical investigation in the adult rabbit model. J Orthop Res. 1992;10:157–166.PubMedCrossRef

10.

Brent AE, Schweitzer R, Tabin CJ. A somitic compartment of tendon progenitors. Cell. 2003;113:235–248.PubMedCrossRef

11.

Carpenter JE, Thomopoulos S, Flanagan CL, DeBano CM, Soslowsky LJ. Rotator cuff defect healing: a biomechanical and histologic analysis in an animal model. J Shoulder Elbow Surg. 1998;7:599–605.PubMedCrossRef

12.

Chan BP, Fu SC, Qin L, Rolf C, Chan KM. Supplementation-time dependence of growth factors in promoting tendon healing. Clin Orthop Relat Res. 2006;448:240–247.PubMedCrossRef

13.

Chhabra A, Tsou D, Clark RT, Gaschen V, Hunziker EB, Mikic B. GDF-5 deficiency in mice delays Achilles tendon healing. J Orthop Res. 2003;21:826–835.PubMedCrossRef

14.

Choi HR, Kondo S, Hirose K, Ishiguro N, Hasegawa Y, Iwata H. Expression and enzymatic activity of MMP-2 during healing process of the acute supraspinatus tendon tear in rabbits. J Orthop Res. 2002;20:927–933.PubMedCrossRef

15.

Clark SC, Jones MW, Choudhury RR, Smith E. Bilateral patellar tendon rupture secondary to repeated local steroid injections. J Accid Emerg Med. 1995;12:300–301.PubMed

16.

Cohen DB, Kawamura S, Ehteshami JR, Rodeo SA. Indomethacin and celecoxib impair rotator cuff tendon-to-bone healing. Am J Sports Med. 2006;34:362–369.PubMedCrossRef

17.

Cope MR, Ali A, Bayliss NC. Biceps rupture in body builders: three case reports of rupture of the long head of the biceps at the tendon-labrum junction. J Shoulder Elbow Surg. 2004;13:580–582.PubMedCrossRef

18.

Darlington LG, Coomes EN. The effects of local steroid injection for supraspinatus tears. Rheumatol Rehabil. 1977;16:172–179.PubMed

19.

David HG, Green JT, Grant AJ, Wilson CA. Simultaneous bilateral quadriceps rupture: a complication of anabolic steroid abuse. J Bone Joint Surg Br. 1995;77:159–160.PubMed

20.

Docheva D, Hunziker EB, Fässler R, Brandau O. Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol Cell Biol. 2005;25:699–705.PubMedCrossRef

21.

Evans NA. Current concepts in anabolic-androgenic steroids. Am J Sports Med. 2004;32:534–542.PubMedCrossRef

22.

Fealy S, Adler RS, Drakos MC, Kelly AM, Allen AA, Cordasco FA, Warren RF, O’Brien SJ. Patterns of vascular and anatomical response after rotator cuff repair. Am J Sports Med. 2006;34:120–127.PubMedCrossRef

23.

Forslund C, Aspenberg P. Tendon healing stimulated by injected CDMP-2. Med Sci Sports Exerc. 2001;33:685–687.PubMed

24.

Forslund C, Aspenberg P. Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2. Am J Sports Med. 2003;31:555–559.PubMed

25.

Forslund C, Rueger D, Aspenberg P. A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2, and -3 for tendon healing in rats. J Orthop Res. 2003;21:617–621.PubMedCrossRef

26.

Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am. 2004;86:219–224.PubMed

27.

Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006;88:2027–2034.PubMedCrossRef

28.

Gazielly DF, Gleyze P, Montagnon C. Functional and anatomical results after rotator cuff repair. Clin Orthop Relat Res. 1994;304:43–53.PubMed

29.

Gelberman RH, Woo SL, Lothringer K, Akeson WH, Amiel D. Effects of intermittent passive mobilization on healing canine flexor tendons. J Hand Surg Am. 1982;7:170–175.PubMed

30.

Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. 2000;82:505–515.PubMed

31.

Gerber C, Schneeberger AG, Perren SM, Nyffeler RW. Experimental rotator cuff repair. a preliminary study. J Bone Joint Surg Am. 1999;81:1281–1290.PubMed

32.

Gomez M, Woo SL, Amiel D, Harwood F, Kitabayashi L, Matyas J. The effects of increased tension on healing medial collateral ligaments. Am J Sports Med. 1991;19:347–354.PubMedCrossRef

33.

Haraldsson BT, Langberg H, Aagaard P, Zuurmond AM, van El B, Degroot J, Kjaer M, Magnusson SP. Corticosteroids reduce the tensile strength of isolated collagen fascicles. Am J Sports Med. 2006;34:1992–1997.PubMedCrossRef

34.

Harryman DT, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA. Repairs of the rotator cuff: correlation of functional results with integrity of the cuff. J Bone Joint Surg Am. 1991;73:982–989.PubMed

35.

Holmbeck K, Bianco P, Chrysovergis K, Yamada S, Birkedal-Hansen H. MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth. J Cell Biol. 2003;163:661–671.PubMedCrossRef

36.

Inhofe PD, Grana WA, Egle D, Min KW, Tomasek J. The effects of anabolic steroids on rat tendon: an ultrastructural, biomechanical, and biochemical analysis. Am J Sports Med. 1995;23:227–232.PubMedCrossRef

37.

Kawamura S, Ying L, Kim HJ, Dynybil C, Rodeo SA. Macrophages accumulate in the early phase of tendon-bone healing. J Orthop Res. 2005;23:1425–1432.PubMed

38.

Kennedy JC, Willis RB. The effects of local steroid injections on tendons: a biomechanical and microscopic correlation study. Am J Sports Med. 1976;4:11–21.PubMedCrossRef

39.

Kobayashi M, Itoi E, Minagawa H, Miyakoshi N, Takahashi S, Tuoheti Y, Okada K, Shimada Y. Expression of growth factors in the early phase of supraspinatus tendon healing in rabbits. J Shoulder Elbow Surg. 2006;15:371–377.PubMedCrossRef

40.

Laseter JT, Russell JA. Anabolic steroid-induced tendon pathology: a review of the literature. Med Sci Sports Exerc. 1991;23:1–3.PubMed

41.

Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH. Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy. 2004;20:899–910.PubMed

42.

Lin TW, Cardenas L, Glaser DL, Soslowsky LJ. Tendon healing in interleukin-4 and interleukin-6 knockout mice. J Biomech. 2006;39:61–69.PubMedCrossRef

43.

Liow RY, Tavares S. Bilateral rupture of the quadriceps tendon associated with anabolic steroids. Br J Sports Med. 1995;29:77–79.PubMed

44.

Lou J, Tu Y, Burns M, Silva MJ, Manske P. BMP-12 gene transfer augmentation of lacerated tendon repair. J Orthop Res. 2001;19:1199–1202.PubMedCrossRef

45.

Lu H, Qin L, Fok P, Cheung W, Lee K, Guo X, Wong W, Leung K. Low-intensity pulsed ultrasound accelerates bone-tendon junction healing: a partial patellectomy model in rabbits. Am J Sports Med. 2006;34:1287–1296.PubMedCrossRef

46.

Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes: a constant threat. Toxicol Lett. 2005;158:167–175.PubMedCrossRef

47.

Marqueti RC, Parizotto NA, Chriguer RS, Perez SE, Selistre-de-Araujo HS. Androgenic-anabolic steroids associated with mechanical loading inhibit matrix metallopeptidase activity and affect the remodeling of the achilles tendon in rats. Am J Sports Med. 2006;34:1274–1280.PubMedCrossRef

48.

Miles JW, Grana WA, Egle D, Min KW, Chitwood J. The effect of anabolic steroids on the biomechanical and histological properties of rat tendon. J Bone Joint Surg Am. 1992;74:411–422.PubMed

49.

Murray DH, Kubiak EN, Jazrawi LM, Araghi A, Kummer F, Loebenberg MI, Zuckerman JD. The effect of cartilage-derived morphogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. J Shoulder Elbow Surg. 2007;16:251–254.PubMedCrossRef

50.

Nakase T, Sugamoto K, Miyamoto T, Tsumaki N, Luyten FP, Inui H, Myoui A, Tomita T, Yoshikawa H. Activation of cartilage-derived morphogenetic protein-1 in torn rotator cuff. Clin Orthop Relat Res. 2002;399:140–145.PubMedCrossRef

51.

Paoloni JA, Appleyard RC, Nelson J, Murrell GA. Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial. Am J Sports Med. 2005;33:806–813.PubMedCrossRef

52.

Perry SM, McIlhenny SE, Hoffman MC, Soslowsky LJ. Inflammatory and angiogenic mRNA levels are altered in a supraspinatus tendon overuse animal model. J Shoulder Elbow Surg. 2005;14:S79–S83.CrossRef

53.

Rickert M, Jung M, Adiyaman M, Richter W, Simank HG. A growth and differentiation factor-5 (GDF-5) coated suture stimulates tendon healing in an Achilles tendon model in rats. Growth Factors. 2001;19:115–126.PubMedCrossRef

54.

Rickert M, Wang H, Wieloch P, Lorenz H, Steck E, Sabo D, Richter W. Adenovirus-mediated gene transfer of growth and differentiation factor-5 into tenocytes and the healing rat achilles tendon. Connect Tiss Res. 2005;46:175–183.CrossRef

55.

Rodeo SA, Potter HG, Kawamura S, Turner AS, Kim HJ, Atkinson BL. Biologic augmentation of rotator cuff tendon healing using a mixture of osteoinductive growth factors: an experimental study in sheep. J Bone Joint Surg Am. 2007;89:2485–2497.PubMedCrossRef

56.

Rubin C, Bolander M, Ryaby JP, Hadjiargyrou M. The use of low-intensity ultrasound to accelerate the healing of fractures. J Bone Joint Surg Am. 2001;83:259–270.PubMedCrossRef

57.

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;128:3855–3866.PubMed

58.

Scutt N, Rolf CG, Scutt A. Glucocorticoids inhibit tenocyte proliferation and tendon progenitor cell recruitment. J Orthop Res. 2006;24:173–182.PubMedCrossRef

59.

Shukunami C, Takimoto A, Oro M, Hiraki Y. Scleraxis positively regulates the expression of tenomodulin, a differentiation marker of tenocytes. Dev Biol. 2006;298:234–247.PubMedCrossRef

60.

Smith AG, Kosygan K, Williams H, Newman RJ. Common extensor tendon rupture following corticosteroid injection for lateral tendinosis of the elbow. Br J Sports Med. 1999;33:423–424.PubMedCrossRef

61.

Sollender JL, Rayan GM, Barden GA. Triceps tendon rupture in weight lifters. J Shoulder Elbow Surg. 1998;7:151–153.PubMedCrossRef

62.

Spindler KP, Dawson JM, Stahlman GC, Davidson JM, Nanney LB. The biomechanical response to doses of TGF-beta 2 in the healing rabbit medial collateral ligament. J Orthop Res. 2003;21:245–249.PubMedCrossRef

63.

Stannard JP, Bucknell AL. Rupture of the triceps tendon associated with steroid injections. Am J Sports Med. 1993;21:482–485.PubMedCrossRef

64.

Sweetnam R. Corticosteroid arthropathy and tendon rupture. J Bone Joint Surg Br. 1969;51:397–398.PubMed

65.

Taylor DC, Brooks DE, Ryan JB. Anabolic-androgenic steroid administration causes hypertrophy of immobilized and nonimmobilized skeletal muscle in a sedentary rabbit model. Am J Sports Med. 1999;27:718–727.PubMed

66.

Thomopoulos S, Soslowsky LJ, Flanagan CL, Tun S, Keefer CC, Mastaw J, Carpenter JE. The effect of fibrin clot on healing rat supraspinatus tendon defects. J Shoulder Elbow Surg. 2002;11:239–247.PubMedCrossRef

67.

Thomopoulos S, Williams GR, Soslowsky LJ. Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels. J Biomech Eng. 2003;125:106–113.PubMedCrossRef

68.

Triantafillopoulos IK, Banes AJ, Bowman KF Jr, Maloney M, Garrett WE Jr, Karas SG. Nandrolone decanoate and load increase remodeling and strength in human supraspinatus bioartificial tendons. Am J Sports Med. 2004;32:934–943.PubMedCrossRef

69.

Tsai WC, Tang FT, Wong MK, Pang JH. Inhibition of tendon cell migration by dexamethasone is correlated with reduced alpha-smooth muscle actin gene expression: a potential mechanism of delayed tendon healing. J Orthop Res. 2003;21:265–271.PubMedCrossRef

70.

Uggen JC, Dines J, Uggen CW, Mason JS, Razzano P, Dines D, Grande DA. Tendon gene therapy modulates the local repair environment in the shoulder. J Am Osteopath Assoc. 2005;105:20–21.PubMed

71.

Virchenko O, Fahlgren A, Skoglund B, Aspenberg P. CDMP-2 injection improves early tendon healing in a rabbit model for surgical repair. Scand J Med Sci Sports. 2005;15:260–264.PubMedCrossRef

72.

Visuri T, Lindholm H. Bilateral distal biceps tendon avulsions with use of anabolic steroids. Med Sci Sports Exerc. 1994;26:941–944.PubMed

73.

Walsh WR, Stephens P, Vizesi F, Bruce W, Huckle J, Yu Y. Effects of low-intensity pulsed ultrasound on tendon-bone healing in an intra-articular sheep knee model. Arthroscopy. 2007;23:197–204.PubMedCrossRef

74.

Wei AS, Callaci JJ, Juknelis D, Marra G, Tonino P, Freedman KB, Wezeman FH. The effect of corticosteroid on collagen expression in injured rotator cuff tendon. J Bone Joint Surg Am. 2006;88:1331–1338.PubMedCrossRef

75.

Wolfman NM, Hattersley G, Cox K, Celeste AJ, Nelson R, Yamaji N, Dube JL, DiBlasio-Smith E, Nove J, Song JJ, Wozney JM, Rosen V. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest. 1997;100:321–330.PubMed

Title: Biological Augmentation of Rotator Cuff Tendon Repair
Authors: David Kovacevic, BS
Scott A. Rodeo, MD
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Clinical Orthopaedics and Related Research® / Issue 3/2008
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-007-0112-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biological Augmentation of Rotator Cuff Tendon Repair

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2008

Case Report

Reverse Shoulder Arthroplasty Combined with a Modified Latissimus Dorsi and Teres Major Tendon Transfer for Shoulder Pseudoparalysis Associated with Dropping Arm

Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

Case Report

Aneurysmal Bone Cysts Recur at Juxtaphyseal Locations in Skeletally Immature Patients

Contribution of the Reverse Endoprosthesis to Glenohumeral Kinematics