Keratin Scaffold Formulation Impacts rhBMP-2 Biodistribution and Bone Regeneration in a Rat Femur Defect Model

Abstract

Background: Treatment for nonunion in long bones remains a clinical need. Collagen sponges loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) are potential grafts but have limited FDA-approved applications due to safety concerns associated with rapid collagen resorption and burst release of rhBMP-2 in vivo . This work investigates keratin proteins obtained from human hair as a potential rhBMP-2 biomaterial carrier. Keratins are an appealing carrier because the extent of disulfide crosslinking can be modulated by the form of keratin present, thus allowing control over the rate of scaffold degradation. Methods: The two forms of keratin used to formulate carriers were reductively extracted keratin called kerateine (KTN) that can form disulfide crosslinks and oxidatively extracted keratin called keratose (KOS) that does not form disulfide crosslinks. Five formulations of freeze-dried keratin scaffolds containing variable amounts of KOS and KTN were fabricated and implanted into a critically-sized rat femur defect model. Results: A 50:50 KOS:KTN formulation with rhBMP-2 showed the same level of bone bridging, bone mineral density, and bone volume as collagen with rhBMP-2 by 8 weeks as determined by μ-CT. Scaffolds with the 50:50 KOS:KTN or 100% KTN showed approximately fourfold higher retention of fluorescently-labeled rhBMP-2 at the implant site 1, 3, or 7 days post-implant compared to collagen or 100% KOS scaffolds. The increased retention with 50:50 KOS:KTN or 100% KTN correlated with decreased levels of fluorescent rhBMP-2 in distal organs. Conclusions: Keratin scaffolds could provide comparable levels of bone regeneration as collagen carriers with improved safety profiles suitable for use in long bone nonunions.

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