Cytokines in rotator cuff degeneration and repair.

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.