Fetal Tissue Engineering for Tendon Regeneration
Restoration of hand and upper extremity function following tendon injures is largely dependent on the reestablishment of the gliding mechanism between the tendon and its surrounding tissue. Post surgical scarring that hinders gliding remains the most problematic aspect of tendon repair. Extensive experimental evidence exists that fetal tissue in the early to mid-gestational age responds to injury in a fundamentally different manner than adult tissue. In general, fetal wound healing occurs at a faster rate and in the absence of scar formation. Importantly, lack of scar formation in fetal tissues has been attributed to the absence of a substantial inflammatory response following injury, obviating the reparative fibrotic response seen in adult tissue. A non-scarring fetal healing response has been observed in skin, articular cartilage, nerve, bone, and tendon injury models. Further more, injured fetal tendon tissue transplanted into an adult environment retains its regenerative healing pattern, suggesting that this scarless pattern is intrinsic to the fetal tendon tissue and not the fetal environment. Harnessing the processes that control the regenerative healing response in fetal animals may enable us to modulate the fibrotic response observed in adults, leading to significant improvement in the clinical treatment of traumatic tendon injuries. The study design employs novel nanofibrous biomaterial scaffolds and a physiologic loading regimen to engineer functional tissue equivalents for tendon regeneration. In addition, a rat rotator cuff supraspinatus tendon injury model will be used to evaluate the efficacy of the engineered constructs in vivo.
Research is currently being conducted to determine the effect of unseeded scaffolds in the rat supraspinatus injury model. Future work will include the addition of a bioreactor to precondition both the adult and fetal cell seeded scaffolds before implantation. Key factors such as culture duration, scaffold loading and frequency and cell seeding density will all be evaluated. Once these steps have been completed, preconditioned, seeded scaffolds will be implanted in an adult tendon defect to evaluate the elastic and viscoelastic biomechanical properties. Our hypothesis is that the implantation of fetal skin fibroblast-bioabsorbable scaffold composites into adult tendon defects will lead to regenerative healing in a manner intrinsic to fetal tissue, with rapid regeneration of normally aligned collagen fibers, minimal inflammatory cell infiltration, minimal granulation tissue formation, and an absence of scar.