Unveiling the Mechanism of Surface Hydrophilicity‐Modulated Macrophage Polarization

TLDR

Inflammation is increasingly recognized as a key factor influencing fracture healing, with the immune response playing a pivotal role in implant‑mediated osteogenesis. This study demonstrates that altering the surface hydrophilicity of Ti oxide can steer macrophage polarization toward pro‑ or anti‑inflammatory phenotypes to control the immune response. Hydrophilicity modulates fibronectin and fibrinogen adsorption and conformation, activating PI3K or NF‑κB pathways through selective integrin β1/β2 expression to influence macrophage behavior. Hydrophilic surfaces enhance anti‑inflammatory and pro‑healing macrophage activity, confirming the mechanism and guiding the design of implant materials with improved anti‑inflammatory and osteogenic properties.

Abstract

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.