Microporous structures on mineralized collagen mediate bone restoration by promoting nucleolin secretion to induce macrophage M2 polarization.

Bone defects rehabilitation is one of the difficulties in oral clinical practice. Implanted biomaterials have pivotal effects on the regeneration in critical bone defects, but the immunologic reactions arising from their entering into the body are difficult to control. Biomaterials characteristics can effect the immune response, and thus, interfere with the skeletal system. Our previous study found that microporous structures on mineralized collagen (MC) modulated macrophage polarization in bone immune response thereby promoting osteogenic differentiation of osteoblasts. However, the role of MC with various microporous structures in guiding bone rejuvenation in vivo is still unknown and the specific mechanism of crosstalk between MC, macrophages and osteoblasts during bone repair is poorly understood. In this research, we investigated the impact and mechanism of MC with different pore sizes on bone regeneration. The results showed that MC with a medium pore size (85 μm) promoted bone defects repair significantly, M2 macrophage polarization and nucleolin (NCL) expression in macrophages. And the fanconi anemia pathway was implicated in this process. We found that NCL regulated macrophage polarization towards M2 by inhibiting and overexpressing NCL in macrophages. This study will provide a new idea for using biomaterials to regulate host immune response and promote bone regeneration.