Hierarchical Composite Scaffold with Deferoxamine Delivery System to Promote Bone Regeneration via Optimizing Angiogenesis

A bone defect refers to the loss of bone tissue caused by trauma or lesion. Bone defects result in high morbidity and deformity rates worldwide. Autologous bone grafting has been widely applied in clinics as the gold standard of treatment; however, it has limitations. Hence, bone tissue engineering has been proposed and developed as a novel therapeutic strategy for treating bone defects. Rapid and effective vascularization is essential for bone regeneration. In this study, a hierarchical composite scaffold with deferoxamine (DFO) delivery system, DFO@GMs-pDA/PCL-HNTs (DGPN), is developed, focusing on vascularized bone regeneration. The hierarchical structure of DGPN imitates the microstructure of natural bone and interacts with the local extracellular matrix, facilitating cell adhesion and proliferation. The addition of 1 wt% of halloysite nanotubes (HNTs) improves the material properties. Hydrophilic and functional groups conferred by polydopamine (pDA) modifications strengthen the scaffold bioactivity. Gelatin microspheres (GMs) protect the pharmacological activity of DFO, achieving local application and sustained release for 7 days. DFO effectively promotes angiogenesis by activating the signaling pathway of hypoxia inducible factor-1 α. In addition, DFO synergizes with HNTs to promote osteogenic differentiation and matrix mineralization. These results indicate that DGPN promotes bone regeneration and accelerates cranial defect healing.