Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair

Background: Rotator cuff tendon heals by formation of an interposed zone of fibrovascular scar tissue. Recent studies demonstrate that transforming growth factor-beta 3 (TGF-β₃) is associated with tissue regeneration and ''scarless'' healing, in contrast to scar-mediated healing that occurs with TGF-β₁. Hypothesis: Delivery of TGF-β₃ in an injectable calcium-phosphate matrix to the healing tendon-bone interface after rotator cuff repair will result in increased attachment strength secondary to improved bone formation and collagen organization and reduced scar formation of the healing enthesis. Study Design: Controlled laboratory study. Methods: Ninety-six male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon followed by acute repair using transosseous suture fixation. Animals were allocated into 1 of 3 groups: (1) repair alone (controls, n = 32), (2) repair augmented by application of an osteoconductive calcium-phosphate (Ca-P) matrix only (n = 32), or (3) repair augmented with Ca-P matrix + TGF-β₃ (2.75 μg) at the tendon-bone interface (n = 32). Animals were euthanized at either 2 weeks or 4 weeks postoperatively. Biomechanical testing of the supraspinatus tendon-bone complex was performed at 2 and 4 weeks (n = 8 per group). Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometry and immunohistochemical localization of collagen types I (COLI) and III (COLIII). Statistical analysis was performed using 2-way analysis of variance with significance set at P <.05. Results: There was significantly greater load to failure of the Ca-P matrix + TGF-β₃ group compared with matrix alone or untreated controls at 4 weeks postoperatively (P =.04). At 2 weeks, microcomputed tomography revealed a larger volume of newly formed bone present at the healing enthesis in both experimental groups compared with the control group. By 4 weeks, this newly formed, woven bone had matured into calcified, lamellar bone. Histomorphometric analysis demonstrated significantly greater fibrocartilage and increased collagen organization at the healing tendon-bone insertion site in both experimental groups compared with the control group at 2 weeks (P =.04). Over time, TGF-β₃ delivery led to greater COLI expression compared with COLIII at the healing enthesis, indicating a more favorable COLI to COLIII ratio with administration of TGF-β₃. Conclusion: Augmentation with an osteoconductive Ca-P matrix at the tendon-bone repair site is associated with new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface in the early postoperative period after rotator cuff repair. The addition of TGF-β₃ significantly improved strength of the repair at 4 weeks postoperatively and resulted in a more favorable COLI/COLIII ratio. Clinical Relevance: The delivery of TGF-β₃ with an injectable Ca-P matrix at the supraspinatus tendon footprint has promise to improve healing after soft tissue repair.