ε-Polylysine-Based Macromolecules with Catalase-Like Activity to Accelerate Wound Healing by Clearing Bacteria and Attenuating Inflammatory Response

Wound healing has remained a critical challenge due to its susceptibility to bacterial infection and the unique biological inflammatory response. Safe and effective therapeutics are still lacking. Biodegradable macromolecules (ε-polylysine-g-ferrocene, EPL-g-Fc) were developed to accelerate wound healing by combating bacterial infection and attenuating inflammatory responses. The biodegradable macromolecules were prepared via a Schiff-based reaction between ferrocene carboxaldehyde (Fc) and ε-polylysine (EPL). Through the synergistic combination of positive-charged EPL and π-π stacked Fc, the macromolecules possess excellent antibacterial activities. EPL-g-Fc with catalase-like activity could modulate the oxidative microenvironment in mammalian cells and zebrafish by catalyzing H2O2 into H2O and O2. EPL-g-Fc could alleviate inflammatory response in vitro. Furthermore, the macromolecules could accelerate bacteria-infected wound healing in vivo. This work provides a versatile strategy for repairing bacteria-infected wounds by eliminating bacteria, modulating oxidative microenvironment, and alleviating inflammatory response.