Thermoresponsive therapeutic alginate hydrogel with bilirubin-loaded polydopamine nanoparticles for enhanced diabetic wound healing

Diabetic wounds, a common and serious complication of diabetes, are characterized by delayed healing, primarily due to excessive accumulation of reactive oxygen species (ROS) and heightened vulnerability to bacterial infection. Herein, to address the urgent need for effective wound healing materials, we developed a thermoresponsive therapeutic hydrogel composite comprising bilirubin-loaded mesoporous polydopamine nanoparticles (BR@mPDA NPs) incorporated into an alginate/Pluronic F127 (A/F) hydrogel matrix. Upon near-infrared (NIR) laser irradiation, mPDA NPs generated a photothermal effect that eradicated more than 90% of bacteria and triggered the controlled release of BR. Furthermore, the A/F hydrogel demonstrated superior biocompatibility by maintaining cell viability above 85% and exhibited favorable hemocompatibility due to the presence of alginate. The incorporation of BR facilitated the polarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype, thereby accelerating wound healing. In vitro experiments demonstrated that the BR@mPDA-A/F hydrogel reduced intracellular ROS levels by approximately 40%, indicating effective ROS scavenging activity. In vivo evaluation also represented significantly accelerated diabetic wound healing, achieving 90.2% wound closure by day 7 compared with 66.4% in the control group, accompanied by enhanced tissue regeneration and no detectable toxicity. Collectively, these findings highlight the BR@mPDA-A/F hydrogel as a promising therapeutic platform for diabetic wound management.