A pH/Enzyme Dual Responsive PMB Spatiotemporal Release Hydrogel Promoting Chronic Wound Repair

Persistent MDR bacterial infection and excessive inflammation are stricken issues in chronic wounds. Currently, developing a microenvironment-responsive hydrogel with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the wound-healing process, but remains a challenge using ordinary assembly. Herein, we propose a pH/enzyme dual responsive PMB spatiotemporal release hydrogel (GelMA/OSSA/PMB), including polymer drug conjugate (Schiff's base reaction between aldehyde groups in OSSA and amino groups in PMB) and photo-crosslinked GelMA. The ingenious combination of novel polymer conjugates (OSSA/PMB) in the GelMA/OSSA/PMB hydrogel shows better bio-safety than equivalent free PMB and is contributes to relase PMB controlly, which helps to kill planktonic bacteria and inhibit biofilm activity in vitro. Notably, it performs better bio-safety on encapsulating hydrophilic active PMB than equivalent free PMB. Simulataneously, GelMA/OSSA/PMB exhibits excellent antibacterial properties and anti-inflammatory activities. MDR P.a -caused infection was effectively cured by the GelMA/OSSA/PMB hydrogel in vivo, and thereby the wound closure at the inflammatory phase was promoted significantly. Further, GelMA/OSSA/PMB accelerated the sequential phases in wound repair progress. GelMA/OSSA/PMB hydrogel showed the potential of microenvironment-responsive hydrogels in chronic wound dressings.