A Supramolecular Bifunctional Hydrogel with Zero-Order Release Kinetics to Resist Bacterial Infection and Foreign Body Response of Implants

Supramolecular hydrogels demonstrate considerable potential in drug delivery owing to their distinctive features, including bio-adhesiveness, self-healing behaviors, biodegradability, and biocompatibility. Nevertheless, the fabrication of supramolecular hydrogels utilizing exclusively clinically approved drugs remain challenging, typically necessitating chemical modifications of the drugs to facilitate the gelation process. In this study, we report a novel type of supramolecular hydrogel through the direct assembly of two clinically approved drugs, tobramycin and mycophenolic acid, via combined electrostatic and hydrophobic interactions. The hydrogel shows adjustable bio-adhesiveness, zero-order release kinetics, good biocompatibility, and maintained antibacterial and immunosuppressive activities. It efficiently inhibits bacterial infections and foreign body responses, and accelerates tissue healing in several subcutaneous/intraosseous implantation models accompanied by bacteria infections. This work provides a facile and promising strategy to fabricate supramolecular hydrogels with stable drug release kinetics using clinically approved drugs.