Special issue on rotator cuff biology and healing
Cytokines in rotator cuff degeneration and repair

https://doi.org/10.1016/j.jse.2011.09.020Get rights and content

The pathogenesis of rotator cuff degeneration remains poorly defined, and the incidence of degenerative tears is increasing in the aging population. Rates of recurrent tear and incomplete tendon-to-bone healing after repair remain significant for large and massive tears. Previous studies have documented a disorganized, fibrous junction at the tendon-to-bone interface after rotator cuff healing that does not recapitulate the organization of the native enthesis. Many biologic factors have been implicated in coordinating tendon-to-bone healing and maintenance of the enthesis after rotator cuff repair, including the expression and activation of transforming growth factor-β, basic fibroblast growth factor, platelet-derived growth factor-β, matrix metalloproteinases, and tissue inhibitors of metalloproteinases. Future techniques to treat tendinopathy and enhance tendon-to-bone healing will be driven by our understanding of the biology of this healing process after rotator cuff repair surgery. The use of cytokines to provide important signals for tissue formation and differentiation, the use of gene therapy techniques to provide sustained cytokine delivery, the use of stem cells, and the use of transcription factors to modulate endogenous gene expression represent some of these possibilities.

Section snippets

Pathogenesis of tendinopathy

The pathogenesis of rotator cuff tendinopathy is multifactorial and reflects a combination of mechanical and biologic factors. Rotator cuff tendinosis may be secondary to disorganization in collagen fibril morphology and tendon ultrastructure. Prior studies have documented the histopathologic changes associated with rotator cuff tendinopathy, including loss of cellularity, thinning and disorganization of tendon fibers, increased granulation tissue, and fibrocartilaginous changes.17, 27, 55

Rotator cuff repair and tendon-to-bone healing

Rotator cuff healing occurs by reactive scar formation rather than by regeneration of a histologically normal enthesis (Fig. 1). The overall structure, composition, and organization of a normal insertion site with transition from unmineralized fibrocartilage to mineralized fibrocartilage and bone is not achieved. The poor healing response is multifactorial but likely relates to insufficient and disorganized expression of cytokines to direct formation of the complex structure and composition of

Role of specific cytokines in rotator cuff tendon-to-bone repair

Given the complex cascade of cellular and molecular signals at the healing tendon–bone interface, attention has turned toward methods to augment the biologic response after rotator cuff repair surgery. Because cytokines play important roles in cell chemotaxis, proliferation, matrix synthesis, and cell differentiation, these molecules have the potential to improve rotator cuff tendon healing via autocrine and paracrine signaling. The healing process is a carefully timed and organized event

Conclusion

Improved understanding of the biology of tendon–bone healing has led to the application of specific cytokines to treat tendinopathy and augment healing after rotator cuff repair surgery. Improved healing with cytokines depends on the dosage, timing, and delivery vehicle used, and a multifactorial approach will likely be needed to optimize the healing environment. Osteoinductive cytokines can improve bone formation at the healing tendon–bone interface. BMP-12, BMP-13, and BMP-14 increase

Disclaimer

The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.

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