Effect of Scaffold-delivery Growth Factors in Rotator Cuff Repair

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 DESCRIPTION (provided by applicant): Rotator cuff tendon tears are a common problem that often require surgical repair. However, the success of repair has been mixed, with many patients experiencing tendon re-tears due to failed healing. Following cuff repair failure, glenohumeral joint degenerative changes can ensue, resulting in further pain and dysfunction. Even when healing does occur, repaired tendon rarely achieves functionality equivalent to the pre-injured state. Effective tendon healing is largely inhibited by its inherently poor cellularity and vascularization, preventing adequate matrix production and nutrient delivery. To facilitate timely and robust healing, tissue engineering techniques have been utilized, including the delivery of growth factors. Transforming growth factor ß (TGFß) stimulates tendon cell proliferation and the expression of extracellular matrix proteins such as collagen I and III that contribute to the restoration of tendon mechanical strength. Basic fibroblast growth factor (bFGF) has both angiogenic and mitogenic properties, encourages tissue remodeling, and is known to be upregulated in the initial stages of wound healing. These growth factors both play important roles in the repair process. However, various issues with growth factor delivery have produced only modest improvements in healing. To address these issues, we developed a nanofibrous biomaterial scaffold and microsphere drug delivery system that can be fine-tuned to spatially and temporally control drug release. This approach, coupled with our well-established in vivo rat rotator cuff model, allows us to address several research questions. The overall objective of this study is to determine the role, and mechanisms of action, of controlled delivery of individual targeted tendon repair-related growth factors to improve tissue properties and joint mechanics after injury. Our specific aims are: Aim 1: To develop and characterize electrospun nanofibrous scaffolds incorporating microspheres that will deliver sustained release profiles for TGFßand bFGF and Aim 2: To determine effects of local delivery of a growth factor on tendon healing through a focused set of in vivo rat rotator cuff studies and associated outcome measures. These analyses will determine the effect of sustained growth factor delivery on tendon healing in a controlled system. Results will provide the framework to develop an optimized tissue engineering approach to supplement normal healing responses. Ultimately, this will provide physicians with tools to more effectively treat patients with tendon injuries. Rotator cuff tears are the most common diagnosis encountered in the shoulder clinic at the Philadelphia Veterans Affairs Medical Center. The beneficial effects of sustained local delivery of growth factors via a nanofibrous scaffold at the rotator cuff repair sie has the potential to positively affect surgical outcomes in veterans, both young and old, with acute combat related injuries and chronic degenerative conditions alike.