Responsive multifunctional hydrogels emulating the chronic wounds healing cascade for skin repair.

It remains challenging to cure chronic diabetic wounds due to its' harsh microenvironment and poor tissue regeneration ability. At present, bacteria elimination, inflammatory response suppression and angiogenesis orderly render an important paradigm for chronic diabetic wound treatment. Herein, smart-responsive multifunctional hydrogels were developed to improve chronic diabetic wound healing, which could quickly respond to the acidic environment of the diabetic wound site and mediate multistage sequential delivery of silver and curcumin-loaded polydopamine nanoparticles (PDA@Ag&Cur NPs) and vascular endothelial growth factor (VEGF). PDA@Ag&Cur NPs and VEGF endowed the hydrogels with antibacterial, anti-inflammatory and angiogenesis performances, respectively. The in vitro and in vivo experiments confirmed that our multistage drug delivery hydrogels could effectively eliminate bacteria, relieve inflammatory response, and induce angiogenesis, hence accelerating the closure of chronic diabetic wounds. In conclusion, we highlighted the importance of multistage manipulation in wound healing and offered a combinatorial therapeutic strategy to sequentially deliver drugs exactly aiming at the dynamic wound healing stages.