MOF-incorporated hydrogel for on-demand wound healing

Wound healing constitutes a complex biological process that involves hemostasis, inflammation, proliferation, and remodeling. Reactive oxygen species (ROS) serve crucial roles but act as dual-edged mediators in this process. Previous strategies have predominantly focused on ROS scavenging to mitigate oxidative stress; however, insufficient ROS levels can hinder the early stages of repair. Consequently, an on-demand ROS generation strategy offers a promising approach to modulate the wound microenvironment. In this study, we developed hydrogels incorporated with metal-organic frameworks (MOFs) as light-responsive platforms for controlled wound healing. Gelatin-based hydrogels were crosslinked via a thiol-ene reaction and disulfide bond formation. MOF hydrogels were synthesized by mixing two types of MOF dispersions (PCBA@PCN-222 and PCN-222) with polymer solutions. The hydrogels exhibited no significant variation in phase transition time (127 to 140 secs), regardless of MOF type or concentration. Rheological analysis confirmed their mechanical properties (G’: 206 to 266 Pa). The MOF hydrogels demonstrated ROS generation dependent on irradiation duration. Notably, PCBA@PCN-222 hydrogels produced higher ROS levels compared to PCN-222 hydrogels. Both MOF dispersions and hydrogels exhibited excellent biocompatibility across concentrations ranging from 0.01 to 100 µM, maintaining cell viability above 80%. Cytotoxicity assays under light irradiation showed no significant toxicity after 1 min; however, a 5-min irradiation induced notable cytotoxicity in PCN-222 hydrogels. Additionally, histological examination of major organs was performed to evaluate systemic toxicity. Based on these findings, subsequent in vivo studies will investigate wound closure rates and elucidate underlying biological mechanisms. In conclusion, this MOF hydrogel system is anticipated to serve as a bioactive and controllable platform for wound healing through light-induced ROS generation.