Vascular Derived ECM Improves Therapeutic Index of BMP-2 and Drives Vascularized Bone Regeneration

Vascularized osteogenesis is essential for successful bone regeneration, yet its realization during large size bone defect healing remains challenging due to the difficulty to couple multiple biological processes. Herein, harnessing the intrinsic angiogenic potential of vascular derived extracellular matrix (vECM) and its specific affinity to growth factors, a vECM/GelMA based hybrid hydrogel delivery system is constructed to achieve optimized bone morphogenetic protein-2 (BMP-2) therapeutic index and provide intrinsic angiogenic induction during bone healing. The incorporation of vECM not only effectively regulates BMP-2 kinetics to match the bone healing timeframe, but also promotes angiogenesis both in vitro and in vivo. In vivo results also show that vECM-mediated BMP-2 release remarkably enhances vascularized bone formation for critical size bone defects. In particular, blood vessel ingrowth stained with CD31 marker in the defect area is substantially encouraged over the course of healing, suggesting incorporation of vECM served roles in both angiogenesis and osteogenesis. Thus, the authors' study exemplifies that affinity of growth factor towards ECM may be a promising strategy to be leveraged to develop sophisticated delivery systems endowed with desirable properties for regenerative medicine applications.