Chemo-physical loading of exosomes on porous titanium for improved soft tissue integration

Establishing a durable soft tissue seal around dental implants is critical for preventing peri-implantitis, yet efficient loading of exosomes onto titanium surfaces remains challenging. Here, a dual-functional coating was developed on anodized porous titanium combining stem cell-derived exosomes with cefotaxime sodium via a chemo-physical loading strategy. Porous titanium surfaces exhibited 27% of pores equal/larger than 150 nm at 150 V along with enhanced hydrophilicity. Exosomes loaded via chemo-physical approach achieved the highest loading (30.8 μg/cm²), 2.6-fold higher than chemical grafting alone, while preserving bioactivity. In vitro, porous titanium and exosome-modified surfaces promoted epithelial cell adhesion and induced spindle-shaped fibroblast morphology. In vivo subcutaneous implantation demonstrated good biocompatibility across all groups, as evidenced by absence of necrosis or abscess, and comparable fibrous capsule thickness (~150 μm). No adverse tissue reactions were observed for any of the tested surfaces. These findings demonstrate that chemo-physical loading on optimized porous titanium enables stable, high-capacity exosome immobilization. The resulting dual-functional coating simultaneously promotes soft tissue cell responses and provides antibacterial protection, offering a promising strategy for supporting the tissue healing around dental implants.