Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration

Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce more angiogenic and osteogenic cues. The angiogenesis and osteogenesis capacity of injectable hydrogels could be regulated by tuning the delivery of DFO and BMP-2 independently, resulting in vascularization and bone regeneration in cranial defects. The angiogenesis and osteogenesis outcomes accelerated the regeneration of vascularized bones toward similar composition and structure to natural bones. Therefore, the multiple biophysical and chemical cues provided by the nanofibrous structures, organic-inorganic compositions, and chemical and biochemical angiogenic and osteogenic inducing cues suggest the potential for clinical applicability of these hydrogels in bone tissue engineering.