Anisotropic porous hydrogel fiber coating modified titanium modulates the immune microenvironment to enhance endogenous bone regeneration.

Abstract

Titanium implants remain limited by their intrinsic bioinertness, which compromises osseointegration and long-term stability. Here, we present an immuno-instructive and structurally anisotropic titanium interface designed to promote osteogenesis while modulating the osteoimmune microenvironment. A biomimetic hydrogel fibrous coating composed of nano-hydroxyapatites, gelatin methacryloyl, and silk fibroin was engineered via electrospinning and multimodal crosslinking to generate aligned topographical cues. The anisotropic architecture guided bone marrow stromal cells alignment and migration through cytoskeletal remodeling associated with mechanosensitive responses, while concurrently influencing the local immune milieu by suppressing M1 polarization and promoting M2 transition. These results indicate that the coating exhibited immunomodulatory potential by reducing inflammatory and oxidative stress in macrophages, while also directly supporting osteogenic signaling and matrix mineralization in BMSCs. In vivo, the modified implants reduced early fibrotic encapsulation and promoted peri-implant bone formation, supporting a favorable osteoimmune microenvironment for bone integration. These findings suggest that integrating topographical anisotropy with bioactive hydrogel chemistry provides a promising strategy for enhancing the biological performance of titanium implants and promoting osseointegration.