This study demonstrates that an adhesive implant-tissue interface can mitigate fibrous capsule formation in various animal models, including rats, mice, humanized mice, and pigs. The adhesive interface, composed of a polyurethane mock device and an adhesive layer, reduces inflammatory cell infiltration at the implant-tissue interface compared to non-adhesive implants. Histological analysis shows that the adhesive interface does not form observable fibrous capsules on diverse organs over 12 weeks in vivo. In vitro studies, including protein adsorption assays, multiplex Luminex assays, quantitative PCR, immunofluorescence, and RNA sequencing, validate these findings. Additionally, the study shows that the adhesive interface enables long-term bidirectional electrical communication in a rat model. These results suggest that adhesive anti-fibrotic interfaces offer a promising strategy for long-term implant-tissue integration.This study demonstrates that an adhesive implant-tissue interface can mitigate fibrous capsule formation in various animal models, including rats, mice, humanized mice, and pigs. The adhesive interface, composed of a polyurethane mock device and an adhesive layer, reduces inflammatory cell infiltration at the implant-tissue interface compared to non-adhesive implants. Histological analysis shows that the adhesive interface does not form observable fibrous capsules on diverse organs over 12 weeks in vivo. In vitro studies, including protein adsorption assays, multiplex Luminex assays, quantitative PCR, immunofluorescence, and RNA sequencing, validate these findings. Additionally, the study shows that the adhesive interface enables long-term bidirectional electrical communication in a rat model. These results suggest that adhesive anti-fibrotic interfaces offer a promising strategy for long-term implant-tissue integration.