Charge-Driven Self-Assembled Microspheres Hydrogel Scaffolds for Combined Drug Delivery and Photothermal Therapy of Diabetic Wounds

The treatment of diabetic wound remains a big clinical challenge. Hydrogel that can provide physical barrier and humidity displays amazing potentials for managing the diabetic wounds healing. Herein, a new charge-driven self-assembled microsphere hydrogel scaffold (SMHS) is reported based on an electric charge interaction, by combining use of black phosphorus (BP)-contained chitosan methacryloyl (CS) microspheres with positive charge and basic fibroblast growth factor-contained hyaluronic acid methacryloyl (HA) microspheres with negative charge. The weak charge attraction among microspheres gives the SMHS the injectable characteristic. Due to the existence of BP, near-infrared (NIR) irradiation has obvious effects on the degradation and drug release behaviors of SMHS. Significantly, SMHS that combines the short-term physical (photothermal) intervention and long-term chemical (drug release) intervention may be promising in spatio-temporal regulation of regenerative microenvironment. SMHS with NIR irradiation (SMHS+NIR) can promote cell proliferation, cell migration, angiogenesis and macrophage polarization. Moreover, in diabetic rat skin wounds, SMHS+NIR significantly accelerates the wound healing process by simultaneously inhibiting the inflammatory response, promoting angiogenesis and tissues remodeling. The outcome of this research not only provides a biomaterial for diabetic wounds healing, but also demonstrates a new strategy for designing novel hydrogel-based biomaterials which have the free editing and combination functions.