Evaluation of bone morphogenetic protein -2 release from keratin scaffolds in vitro and in vivo

Recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used clinically to promote bone healing as an alternative to bone grafting treatment. The rhBMP-2 can stimulate cellular differentiation of osteoprogenitor cells to promote bone healing. However, delivery of rhBMP-2 is a challenge since rhBMP-2 has a short half-life and has therefore beefn delivered from collagen sponges implanted at the injury site. While this has led to effective bone regeneration, ectopic bone growth associated with the rapid degradation of collagen and subsequent rhBMP-2 release are clinical problems. We are investigating keratins as alternative rhBMP-2 carriers. Keratins are structural intermediate proteins and can be extracted from human hair. Oxidatively extracted keratin (KOS) cannot achieve disulfide crosslinks whereas reductively extracted keratin (KTN) can form disulfide crosslinks. The rate of degradation of keratin can be tuned by mixing keratose and kerateine in varying ratios. The hypothesis guiding this thesis is that keratin can be formulated with varying ratios of KOS and KTN to modulate the rate of scaffold degradation and thereby control the releasing rate of rhBMP-2. The in vivo release kinetics of rhBMP-2 was assessed by a critically-sized rat femur defect model. The biodistribution of rhBMP-2 after implantation in the critically-sized femur model was assessed in the vital organs.