Fabrication of Multifaceted Angiogenic and Osteogenic Niches With Silk Cryogels for Orchestrating Bone Regeneration

Complicated and dynamic tissue niches that determine the fate of regeneration and the reconstruction of complex niches in vitro remains a challenge. Silk protein nanofiber-based biomaterial matrices with hierarchical cortical and cancellous-like microstructures were developed to induce bone regeneration. Here, hydrophobic simvastatin (SIM) was loaded onto silk nanofibers and further immobilized in the cortical region to mimic natural angiogenesis during bone healing. The matrices maintained biomimetic hierarchical structures after introducing SIM, forming complex microenvironments that contained physical and chemical cues to direct the regenerative mechanisms. The biomimetic niches improved angiogenesis, anti-inflammatory behavior, and osteogenesis, favoring bone regeneration. In vivo studies in rats revealed that blood vessels rapidly grew from the periosteum into the cortical area and then expanded into the cancellous area, similar to natural angiogenesis processes in bone. The bone healing process, characterized by complex anisotropic structures and dynamic vascularization, stimulated high-quality bone regeneration with desirable anisotropic compositions similar to those of natural cortical and cancellous bone. These bioactive matrices with multiple bionic features guided vascular remodeling and bone reconstruction, suggesting potential clinical applications.