Poly-l-lactic acid electrospun membrane with specific morphology promotes bone regeneration through macrophage reprogramming.

Host immune response to bone biomaterials plays a crucial role in influencing the outcome of bone regeneration. In this research, electrospun membranes composed of poly-l-lactic acid (PLLA) with different configurations (aligned and random) and sizes (nanoscale and microscale) were created, and the molecular mechanisms through which PLLA electrospun membranes facilitate bone regeneration were investigated. Firstly, when various material groups were inserted into the rat skull defect model, the bone defect repair was most obvious in the aligned 600 nm group compared with other groups. Then, single-cell RNA sequencing was performed on the bone tissues of the aligned 600 nm group to analyze the characteristics of the immune microenvironment, and the results showed that the effect of PLLA electrospinning membrane on bone regeneration was closely related to the transformation of macrophage subtypes. Finally, the co-culture of macrophages and bone mesenchymal stem cells identified that the molecular pathway involving "PLLA electrospun membrane-M2 macrophage polarization-osteogenic differentiation" could serve as a potential mechanism for bone regeneration. Collectively, the PLLA electrospun membrane with specific morphology promotes bone regeneration by macrophage reprogramming. These findings offer significant insights for the advancement of biomimetic materials aimed at tissue regeneration from the viewpoint of osteo-immunomodulation.