Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds

Recently, the incidence of chronic diabetic wounds increases continuously, and the existing clinical treatment is less effective. Thus, it is an urgent need to solve these problems for better clinical treatment effects. Herein, we prepared a brand-new tailored recombinant human collagen type III (rhCol III) and constructed a multifunctional microenvironment-responsive hydrogel carrier based on multifunctional antibacterial nanoparticles (PDA@Ag NPs) and our tailored rhCol III. The multifunctional smart hydrogel disintegrated quickly at the chronic diabetic wound sites and achieved the programed on-demand release of different therapeutic substances. The first released PDA@Ag NPs showed great antibacterial properties against S. aureus and E. coli. They could kill bacteria rapidly, and also showed antioxidant and anti-inflammatory effects at the wound site. The subsequent release of our tailored rhCol III could promote the proliferation and migration of mouse fibroblasts and endothelial cells during the proliferation and remodeling process of wound healing. Relevant results showed that the multifunctional smart hydrogel could promote the expression levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), decrease the inflammatory response, accelerate the deposition of collagen and increase cell proliferation and angiogenesis, thereby speeding up the healing of infected chronic wounds. In a word, the hydrogel, which took into consideration the complex microenvironment at the wound site and multi-stage healing process, could achieve programmed and responsive release of different therapeutic substances to meet the treatment needs in different wound healing stages. More importantly, our work illustrated the great application potential of our brand-new rhCol III in promoting chronic wound repair and regeneration.