Qingqing Yao, Eric S. Sandhurst, Yangxi Liu, Hongli Sun

Bone morphogenetic proteins (BMPs, e.g., BMP2 and 7) are potent mediators for bone repair, however, their clinical use has been limited by their safety and cost-effectiveness. Therefore, innovative strategies that can improve the efficacy of BMPs, and thereby, use a lower dose of exogenous BMPs are highly desired. Inspired by the natural interaction between extracellular matrix (ECM) and growth factors, we hypothesize that bone matrix-mimicking nanofibrous scaffold functionalized with BMP binding moieties can selectively capture and stabilize BMPs, and thereby, promote BMP-induced osteogenic differentiation. To test our hypothesis, a gelatin nanofibrous scaffold was fabricated using thermally induced phase separation together with a porogen leaching technique (TIPS&P) and functionalized by a BMP-binding peptide (BBP) through cross-linking. Our data indicated that BBP decoration largely improved the BMP2 binding and retention capacity of the nanofibrous scaffolds without compromising their macro/microstructure and mechanical properties. Importantly, the BBP-functionalized gelatin scaffolds were able to significantly promote BMP2-induced osteogenic differentiation. Moreover, BBP alone was able to significantly stimulate endogenous BMP2 expression and improve osteogenic differentiation. Compared to other affinity-based drug delivery strategies, e.g., heparin and antibody-mediated growth factor delivering techniques, we expect BBP-functionalized scaffolds will be a safer, more feasible and selective strategy for endogenous BMP stimulating and binding. Therefore, our data suggests a promising application of using the BBP-decorated gelatin nanofibrous scaffold to stimulate/capture BMPs and promote endogenous bone formation in situ in contrast to relying on the administration of high doses of exogenous BMPs and transplantation of cells.