Enhancing the Osseointegration of Titanium Implants by Modulating M1/M2 Macrophage Polarization through PI3K-Akt Signal Pathway on a “Cortex-like” Microarc Oxidation Coating

Surface modification of titanium implants to enhance osseointegration plays a crucial role in the success of titanium implant therapy; however, the underlying mechanisms remain unclear. This study systematically elucidates the mechanisms underlying osseointegration enhancement in titanium implants with "cortex-like" microarc oxidation (MAO) coatings through material characterization, in vivo and in vitro experiments, and bioinformatics analysis, revealing surface-modified titanium implants synergistically regulate immune response, angiogenesis, and osteogenesis during the process of osseointegration. The "cortex-like" MAO coating exhibits advantageous physicochemical properties, including hybrid micronano-morphology, superhydrophilicity, and stable phase construction. It induces an anti-inflammatory microenvironment that promotes osteogenesis by polarizing macrophages toward the M2 phenotype in vitro. The results of peri-implant bone tissue indicate that the "cortex-like" MAO coating effectively modulates M1/M2 macrophage polarization, promotes angiogenesis, and increases osseointegration in vivo. The transcriptomic analysis further reveals that osseointegration is promoted through the PI3K-Akt signal pathway, which is corroborated using immunohistochemistry assays in vivo. Collectively, these results demonstrate that the "cortex-like" MAO coating enhances osseointegration by mediating macrophage polarization through the PI3K-Akt signal pathway, representing a promising therapeutic mechanism for advancing titanium implant technology.