SrCO3@PCL/PDA composite scaffold promote osteoporotic bone regeneration through immune regulation

Abstract

Bone defects caused by osteoporosis present a significant clinical challenge. The primary obstacles to osteoporotic bone regeneration are the persistent decline in osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and the abnormally high activity of osteoclasts. Emerging research highlights the crucial role of immunomodulation in osteoporosis. Harnessing the immunomodulatory capabilities of bioactive materials to improve the compromised osteoporotic microenvironment may enhance the osteogenic differentiation potential of BMSCs while reducing osteoclast differentiation and resorption. This strategy offers promising avenues for treating osteoporotic bone defects. In this study, we developed an innovative 3D-printed SrCO₃@PCL/PDA composite scaffold. Through 3D printing, the polycaprolactone (PCL) matrix was customized to achieve biomimetic structural and mechanical design. The introduced strontium carbonate (SrCO₃) allows for the responsive release of Sr²⁺ ions in the acidic osteoporotic microenvironment, suppressing osteoclast activity and maintaining a regenerative-friendly environment. The polydopamine (PDA) coating enhances the biocompatibility of the scaffold, thereby promoting cell adhesion and proliferation on its surface. Notably, this novel composite scaffold effectively promotes macrophage polarization towards the M2 phenotype rather than the M1 phenotype, exerting an immunomodulatory effect that improves osteoporotic bone regeneration. In vivo experiments further validated our hypothesis. This innovative composite scaffold offers a promising strategy for the comprehensive treatment of osteoporotic bone defects.