Biodegradable poly(lipoic acid)-based adhesive orchestrates tunable antibacterial activity and controlled H2 release for peri-implant soft tissue integration.

Soft tissue integration around implants is severely compromised by the inflammatory microenvironment, often leading to implant failure. However, due to the bioinert nature of titanium (Ti), effective strategies to regulate this microenvironment remain limited. Herein, we propose a poly(lipoic acid)-based antibacterial polymer (pLAP) enabling controlled molecular hydrogen (H2) release to achieve both antibacterial and pro-regenerative effects for this critical challenge. The pLAP exhibits potent antibacterial activity, achieving killing efficiencies of 90.71% and 94.62% against Staphylococcus aureus and Porphyromonas gingivalis, respectively. Notably, the strong adhesion of pLAP to substrate and its affinity for bacterial membranes contribute to its durable and sustained antibacterial performance. Owing to the encapsulation of H2-loaded TiO2 nanotubes within pLAP and its intrinsic biodegradability, a delayed and sustained H2 release profile is achieved, with H2 levels rising to 427 ppb within 24 h and persisting above 300 ppb for at least 72 h. In vitro and in vivo studies demonstrate that released H2 alleviates oxidative stress and modulates immune responses, with suppression of the JAK1-STAT1 and activation of the JAK3-STAT6 signaling pathways associated with these effects, promoting M2 polarization and enhancing soft tissue integration. Collectively, this work presents a robust and generalizable strategy for regulating the inflammatory microenvironment in peri-implantitis and other implant-associated inflammatory conditions.