Tuning the surface potential to reprogram immune microenvironment for bone regeneration

The induction of a suitable immune microenvironment by implant is essential for fast bone regeneration. Surface potential is a critical factor that influences immune cells behavior. We apply polydopamine coatings on a titanium (Ti) surface to decrease its surface potential. A lower surface potential favored the expression of adhesion-related genes in bone marrow-derived monocytes (BMDMs) by activating the focal adhesion kinase signaling pathway. A lower negative surface potential results in higher electronic repulsion between the surface and the BMDMs, because the cells exhibit negative charged membrane. To resist the repulsive force, Integrin β1 and Integrin β3 in the cell membrane for low surface potential group are upregulated. Furthermore, BMDMs cultured on Ti with low surface potential are more inclined polarize towards anti-inflammatory phenotype (M2) in vitro and in vivo. Whole gene expression analysis reveals that inhibition of the PI3K-Akt-mTOR signaling axis is responsible for the immune regulation ability of Ti with low surface potential. The cytokines secreted by M2 BMDMs promote osteogenic differentiation of a mouse embryo cell line (C3H10T1/2) and increase osteointegration between the implant and newly formed bone. These findings reveal that surface potential regulation is a promising strategy to reprogram the immune microenvironment for bone regeneration and provide insights into developing biomaterials with immunomodulatory functions.