Fabrication of a New Hyaluronic Acid/Gelatin Nanocomposite Hydrogel Coating on Titanium-Based Implants for Treating Biofilm Infection and Excessive Inflammatory Response

Persistent inflammation caused by implant-associated biofilm infections has emerged as a significant clinical issue. While many methods have been developed to give implants great anti-biofilm benefits, the post-inflammatory microenvironment is frequently disregarded. Oxidative stress (OS) due to excessive reactive oxygen species (ROS) is considered to be one of the specific physiological signals of the inflammation microenvironment. Herein, ZIF-90-Bi-CeO2 nanoparticles (NPs) were incorporated into a Schiff-base chemically crosslinked hydrogel composed of aldehyde-based hyaluronic acid and gelatin. Through chemical crosslinking between polydopamine and gelatin, the hydrogel coating adhered to the Ti substrate. The modified Ti substrate gained multimodal antibacterial and anti-biofilm functions, which were attributed to the photothermal effect of Bi NPs, and the release of Zn ions and CeO2 NPs. Notably, CeO2 NPs endowed the system with dual-enzyme (SOD-and CAT-like) catalytic activities. In a rat implant-associated infection (IAI) model, the dual-functional hydrogel had a biofilm-removal ability and regulated OS and inflammatory responses to facilitate osseointegra-tion. The photothermal therapy combined with a host inflammation-microenvironment regulation strategy might provide a novel treatment for biofilm infection and the accompanying excessive inflammation.