Collagen/Heparin Bi‐Affinity Multilayer Modified Collagen Scaffolds for Controlled bFGF Release to Improve Angiogenesis In Vivo

Basic fibroblast growth factor (bFGF) is an important protein for wound healing and angiogenesis in tissue engineering, but the lack of a viable delivery system hampers its clinical application. This study aims to maintain the long‐term controlled release of bFGF by utilizing a collagen/heparin bi‐affinity multilayer delivery system (CHBMDS), which is fabricated by the alternate deposition of negatively charged heparin, positively charged collagen, and CBD‐bFGF (a collagen‐binding domain [CBD] was fused into the native bFGF) via specific or electrostatic interaction. The results show that CHBMDS not only support localized and prolonged release of CBD‐bFGF(over 35 days) but also lead to enhanced angiogenesis (higher density and larger diameter (≈70 µm) of newly formed blood vessels in subcutaneous tissue of SD rat after 5 weeks). This system could act as a versatile approach for bFGF delivery and further improve therapeutic efficacy for injured tissues. Based on the high specific binding ability of fused protein CBD‐bFGF to collagen and heparin, a bi‐affinity multilayer delivery system is developed. It could provide high loading capacity and long‐term controlled release of CBD‐bFGF, which could enhance angiogenesis when implanted in subcutaneous tissue of SD rats.