Unveiling the Mechanism of Surface Hydrophilicity‐Modulated Macrophage Polarization

Abstract With inflammation increasingly recognized as a key factor that influences fracture healing, the immunologic response is considered to play a pivotal role in determining implant‐mediated osteogenesis. Herein, this paper demonstrates that modification of the surface hydrophilicity of Ti surface oxides can be utilized to control immune response by steering the macrophage polarization toward pro‐ or anti‐inflammation phenotype. Enhanced anti‐inflammatory and prohealing performance of macrophages is observed on hydrophilic surfaces compared to hydrophobic ones. Further study on the detailed mechanism demonstrates that the surface hydrophilicity controls specific proteins (fibronectin and fibrinogen) adsorption and conformation, which activate different signaling pathways (PI3K and NF‐κB) through selective expression of integrin β1 or β2 to influence the behaviors of macrophages. Thus, this study presents a mechanism of macrophage polarization modulated by surface hydrophilicity for the surface design of advanced implant materials with satisfactory anti‐inflammatory and osteogenesis‐promoting properties.