Porous PLGA/MBG scaffold enhanced bone regeneration through osteoimmunomodulation

The role of osteoimmunomodulation in orthopedic biomaterials has been demonstrated to be crucial in the regulation of bone repair and regeneration. Macrophages, the primary effector cells in the immune response to biomaterials, are highly heterogeneous and plastic, making them a prime target for immunomodulation. Mesoporous bioactive glass (MBG) is widely recognized for its biocompatibility, osteoconductivity, osteoinductivity, and immunomodulatory properties. However, the impact of MBG content on macrophage response remains unclear. To fill this knowledge gap, we designed a series of hierarchical PLGA-based composite scaffolds with varying MBG contents (0%, 10%, 20% and 40%, named as P, P10M, P20M and P40M, respectively) to investigate the osteoimmunomodulatory effects of these scaffolds. Our findings indicated that the P10M scaffolds showed a faster immune response in the early stage and exhibited superior ability to shift the pro-inflammatory immune microenvironment towards an anti-inflammatory state in the later stage, thereby enhancing the angiogenic potential of HUVECs and the osteogenic capacity of BMSCs. Furthermore, the in vivo implantation demonstrated that the immune microenvironment induced by P10M scaffolds facilitated optimal neovascularization and ectopic bone formation. These findings establish a theoretical foundation for the development of bone immunoregulatory biomaterials doped with MBG, which can effectively promote bone repair and regeneration.