Enhanced angiogenesis of biodegradable iron-doped octacalcium phosphate/poly(lactic-co-glycolic acid) scaffold for potential cancerous bone regeneration

Abstract Metallic therapeutic agents have been widely used in cancer therapy. Iron-based phases that work in concert with porous grafts provide promising strategies for chemotherapy and bone repair after surgery. However, seldom are studies associated to the involvement of extrinsic iron ions in the essential angiogenesis of implantation. In this work, we fabricated a novel iron-loaded biocomposite scaffold with hierarchical channels toward unraveling the influence of Fe3+ release on the angiogenic response of bone grafts. Iron-doped octacalcium phosphate (Fe-OCP) as a viable controllable ferric agent was prepared by homogeneous precipitation through hydrolysis of carbamide. The intervention of Fe3+ altered the crystallochemical properties of OCP with preferential growth of plane (h 0 0) and inhibition growth of plane (0 0 l). Fe-OCP significantly promoted the affinity, viability, proliferation, and angiogenic differentiation of human umbilical vein endothelial cells. The poly(lactic-co-glycolic acid) scaffold with Fe-OCP showed enhanced deposition of bone-like apatites and sustained Fe3+ release under simulated physiological environment. The scaffold supported endothelial cells adhesion and spreading, and notably enhanced angiogenesis with more blood vessels formation and higher specific markers expression. Results suggest that Fe3+ can increase HIF-1α levels and VEGF expression, and promote NO secretion and eNOS production, thus mediating endothelial cells behaviors and angiogenesis. These findings illuminate the remarkable angiogenic capability of iron-loaded grafts for potential cancerous bone repair, which paves the way for developing functionalized bone grafts in therapeutic biomaterials applications.