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 lesions. 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 (BTE) 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), was developed, focusing on vascularized bone regeneration. The hierarchical structure of DGPN imitates the microstructure of natural bone and interacts with the local extracellular matrix (ECM), facilitating cell adhesion and proliferation. The addition of 1 wt% of halloysite nanotubes (HNTs) improved the material properties. Hydrophilic and functional groups conferred by polydopamine (pDA) modifications strengthened the scaffold bioactivity. Gelatin microspheres (GMs) protected the pharmacological activity of DFO, achieving local application and sustained release for seven days. DFO effectively promoted angiogenesis by activating the signaling pathway of hypoxia inducible factor-1 α (HIF-1 α). In addition, DFO synergized with HNTs to promote osteogenic differentiation and matrix mineralization. These results indicated that DGPN promoted bone regeneration and accelerated cranial defect healing. This article is protected by copyright. All rights reserved