Sustained Delivery of Transforming Growth Factor Beta Three Enhances Tendon-to-Bone Healing in a Rat Model

Despite advances in surgical technique, rotator cuff repairs are plagued by a high rate of failure. This failure rate is in part due to poor tendon-to-bone healing; rather than regeneration of a fibrocartilaginous attachment, the repair is filled with disorganized fibrovascular (scar) tissue. Transforming growth factor beta 3 (TGF-beta 3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-beta 3 may enhance tendon-to-bone healing. We hypothesized that: TGF-beta 3 could be released in a controlled manner using a heparin/fibrin-based delivery system (HBDS); and delivery of TGF-beta 3 at the healing tendon-to-bone insertion would lead to improvements in biomechanical properties compared to untreated controls. After demonstrating that the release kinetics of TGF-b3 could be controlled using a HBDS in vitro, matrices were incorporated at the repaired supraspinatus tendon-to-bone insertions of rats. Animals were sacrificed at 14-56 days. Repaired insertions were assessed using histology (for inflammation, vascularity, and cell proliferation) and biomechanics (for structural and mechanical properties). TGF-beta 3 treatment in vivo accelerated the healing process, with increases in inflammation, cellularity, vascularity, and cell proliferation at the early timepoints. Moreover, sustained delivery of TGF-beta 3 to the healing tendon-to-bone insertion led to significant improvements in structural properties at 28 days and in material properties at 56 days compared to controls. We concluded that TGF-beta 3 delivered at a sustained rate using a HBDS enhanced tendon-to-bone healing in a rat model. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1099-1105, 2011