Charge-switchable, anti-oxidative molecule tuned polyelectrolyte multilayered films: Amplified polyelectrolyte diffusivity and accelerated diabetes wound healing

Abstract The local oxidizing microenvironment and bacterial infection, as crucial internal and external factors that hinder the healing of diabetic wounds, are two main issues to be addressed in the design of novel wound dressing materials. As an attempt to provide optimal solution to the aforementioned problems, free-standing (FS) polyelectrolyte multilayer films (PEMs) loaded with bis[2-(4-hydroxyphenyl) benzimidazole] (BHPB) were constructed by layer-by-layer (LBL) self-assembly method. The exponential growth of LBL deposition as well as the film degradation were extensively studied, our results revealed that by pre-assembling polycation with the pH-sensitive BHPB molecule, the polycation diffusivity was largely accelerated thus greatly amplified LBL film growth, ensuring the facile detachment of the PEMs from the substrates to achieve FS films. The increase in BHPB content leaded to faster film growth and slower film degradation and more sustainable BHPB release. In terms of multifunctionality, which was ideal for the design of wound dressing material, the obtained FS films exhibited effective antimicrobial and antioxidant properties thanks to the addition of bioactive BHPB. Notably, unlike traditional antioxidant materials that only neutralize reactive oxygen species (ROS), the BHPB-loaded films stimulated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis, which is a vital intercellular ROS scavenging system blocked by hyperglycemia. Moreover, the wound treated by BHPB-incorporated PEMs exhibited faster healing with increased collagen deposition, enhanced angiogenesis, and rapid re-epithelialization in rat diabetic cutaneous defect models. Overall, in the perspective of cost-effectiveness and simple fabrication, the composite BHPB incorporated FS films reported in the current study showed rather promising potential in the application of diabetic wound healing.