| Effective methods for the treatment of bone injuries that do not heal (non-union) or heal slowly (delayed union) after reduction is a clinical challenge. The use of a collagen sponge to deliver recombinant human bone morphogenetic protein 2 (rhBMP-2) has been shown to be an effective substitute to autografts and allografts for the regeneration of new bone tissue. However, the FDA has limited its approved use to lumbar spinal fusion, open tibial fracture, and craniomaxillofacial injuries, presumably due to ectopic bone growth and other side effects that result from supraphysiological doses of rhBMP-2. Based on our previous findings in femur and mandibular defects, we explored keratin as an alternative carrier system to the existing collagen-based rhBMP-2 delivery system. We have previously used a strategy in which we modulated the levels of disulfide crosslinking in keratin hydrogels based on the extracted form of keratin. This thesis seeks to understand how rhBMP-2 delivered from the keratin hydrogels reaches to cells to achieve bioactivity. In vitro studies were conducted to assess the bioactivity of the soluble rhBMP-2 and matrix-bound rhBMP-2. rhBMP- 2 that remains associated with the keratin carrier is more bioactive than rhBMP-2 that is released from the carrier as a soluble "drug". |
