Near-Infrared Region I-Responsive Composite Scaffolds Promote Bone Defect Repair by Jointly Regulating Angiogenic and Osteogenic Differentiation through Magnesium Ions and Metformin

Abstract

Currently, the repair of bone defects faces multiple challenges, including insufficient angiogenesis and limited osteogenic differentiation capacity, which pose significant obstacles to treatment. In this study, a ternary composite scaffold composed of PCL-nHA-nMgO (PHM) was fabricated using 3D printing technology. After surface modification with a photothermal polydopamine (PDA) coating, a PHM@PDA composite scaffold was obtained. Metformin (Met) and PDA were loaded into GelMA hydrogels to produce GPM hydrogels. The GPM hydrogels were then packed into the PHM@PDA composite scaffolds, resulting in near-infrared region-I (NIR-I)-responsive PHM@PDA/GPM composite scaffolds. The outer GPM layer serves as a three-dimensional in vivo-like microenvironment, providing physical transport channels for cellular nutrient exchange. Upon stimulation by NIR-I, the scaffold enables the dynamic release of Mg2+ and Met, upregulates the expression of the VEGF and KDR, accelerates vascular network reconstruction, and creates a mild microenvironment conducive to cell proliferation. Furthermore, by activating the PI3K/AKT signaling pathway, it promotes the expression of osteogenesis-related factors (such as transcription factor Sp7, alkaline phosphatase, and osteocalcin), thereby accelerating the osteogenic differentiation process. In vivo animal experiments, micro-CT and tissue staining confirmed that, under near-infrared light (NIR-I) stimulation, this scaffold significantly increased bone mineral density, trabecular bone thickness, and trabecular bone count and demonstrated excellent angiogenic effects. In summary, this NIR-I-responsive composite scaffold can meet the dual requirements of reconstructing the vascular network and promoting osteogenic differentiation, enabling personalized precision therapy and offering a promising new treatment strategy for complex bone defects where vascular regeneration and osteogenic differentiation are challenging.