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How to Improve the Biology of Rotator Cuff Healing

Authors: MA Zumstein, P Boileau

References: Presented at SECEC 2009

Currently, the expected rate of structural failure of the muscle-tendon-bone unit after full thickness rotator cuff tendon repair ranges between 70 and 94%1-4. The majority of the failures occur in cases lacking sufficient primary tendon-to-bone restoration within the first few months postoperatively3. Therefore, every attempt should be made to optimize tendon to bone healing after rotator cuff repair. Repair techniques have evolved and eliminated primary tendon to bone fixation by improving suture and anchor material, tendon grasping techniques and tendon mobilization. Although biomechanical studies have shown
stronger repairs with more anchors and sutures, the success of current techniques is more dependent on the biology of
the healing tissue: The healing potential of rotator cuff repair decreases with age: the rate of tendon healing drops down
to 50% after 55 years of age1. This goes along with the established increase in prevalence of tears with age5. The
distal rotator cuff tendons have lower levels of cellular activity6 and large tears have degenerative changes7. Furthermore, osteopenia of the greater tuberosity may affect primary fixation strength and healing biology8. Thus, it appears that new biologic treatment strategies are necessary to support the biological environment to restore the functional unit, specifically in the elderly patients.

Experimental studies have shown that healing after rotator cuff repair comes from the underlying bone9 and the bursal epitenon10, but not from the tenocytes themselves. The repaired insertion is characterized histologically by disorganized tissue with poorer mechanical properties11 and differs from the normal development of the tendon-to-bone insertion12, 13. The formation of a natural four-zone tendonto-bone-insertion14, 15 requires cells, a fibrocartilagenous extracellular matrix (ECM) with collagens I, II, and X and proteoglycans12, different growth factors16, and a 3-dimensional matrix which is conductive17. Although experimental studies with various techniques of biologic augmentation have shown improved healing with inductive
growth factors18-21, it is rather unlike that any one single factor will have the important effect when used in isolation. Autologous thrombocyte concentrates are newly emerging centrifugation techniques to promote tissue healing. The rationale behind their clinical application is based on the recognition of the key role of thrombocytes in the initiation of tissue healing. Thrombocytes adhere, aggregate, form a fibrin mesh and subsequently release a large variety of autologous growth factors and have raised the hope of a safe and easily accessible source. The most common is platelet-rich plasma (PRP), which is made of anticoagulated blood in a two-step procedure using calcium or bovine thrombin to activate and form a fibrin structure secondarily.

PRP has been analyzed experimentally22-28 and employed clinically29-31 with early promising results. However, aside from the lack of clear evidence32 it has the following disadvantages: (1) it time consuming; (2) it is cost effective; (3) it has low-density unstable three-dimensional matrix; and (4) there is a possibility of inducing coagulopathies and cross infection33.
A recent further development of autologous platelet preparations is platelet-rich fibrin (PRF)34, 35. In addition to the favorable PRP-properties, PRF has several advantages: (1) Other than the initial cost of a centrifuge, the preparation of PRF is free; (2) It is a very simple one-step 20 minutes procedure, and is feasible to parallel the surgical intervention in the operating room; (3) it maintains the properties of fibrin adhesives, and the slow polymerization during PRF preparation generates a high density fibrin network with a conductive quality (scaffold) which does not dissolve after application35; this may lead to more efficient cell migration, proliferation and cicatrisation17, 36; (4) the fibrin network directly entraps activated cells, and leads to slow and efficient local delivery of growth factors and cytokines37; (5) platelets and leucocytes are collected with high efficiency, and are activated and preserved in a healthy state.

In summary, PRF may be a potentially advantageous source of local applied growth factors in rotator cuff tendon repair. However, any questions remain unanswered and let open a huge field for future researches. Are chronically degenerated rotator cuff tenocytes able to proliferate and produce the collagens and proteoglycans of a natural tendon to bone insertion? Are they able to reverse potential adverse effects of previous steroid injections? Is PRF able to store and release growth factors over time? What is the role of leucocytes and which is the best protocol to get the highest growth factor release over time? Is the application of PRF feasible and reproducible during rotator cuff repair? Do we get an earlier and higher vascularization response subsequent to PRF application? Do we get an increased watertight restoration of the rotator cuff insertion using PRF as a local growth factor delivery system? It is our hope to bring some answers in the closed future.


REFERENCES:

1. Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic repair of fullthickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. Jun 2005;87(6):1229-1240.
2. 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. February 1, 2004 2004;86(2):219-224.
3. Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. Apr 2000;82(4):505-515.
4. Zumstein MA, Jost B, Hempel J, Hodler J, Gerber C. The Clinical and Structural Long-Term Results of Open Repair of Massive Tears of the Rotator Cuff. J Bone Joint Surg Am. November 1, 2008 2008;90(11):2423-2431.
5. Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am. Aug 2006;88(8):1699-1704.
6. Matthews TJ, Smith SR, Peach CA, Rees JL, Urban JP, Carr AJ. In vivo measurement of tissue metabolism in tendons of the rotator cuff: IMPLICATIONS FOR SURGICAL MANAGEMENT. J Bone Joint Surg Br. May 2007;89(5):633-638.
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8. Meyer DC, Fucentese SF, Koller B, Gerber C. Association of osteopenia of the humeral head with full-thickness rotator cuff tears. J Shoulder Elbow Surg. May-Jun 2004;13(3):333-337.
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