pH-sensitive PβAE/PGS hydrogels for controlled release of SMV and CIP: enhanced wound healing and targeted immunomodulatory properties for efficient skin regeneration

Abstract

Insufficient collagen deposition and excessive inflammation pose significant challenges to the healing process in full-thickness skin wounds. One solution is the sustained release of SMV and CIP to modulate immune responses, promote re-epithelialization, and accelerate wound healing. It is the objective of the present study to enhance wound healing through regulated release of SMV and CIP from P beta AE/PGS (PP)-based hydrogels. The impacts of pH variation on swelling characteristics, degradation behavior, and drug delivery are investigated using a First-order model for the release kinetics of CIP and a Zero-order one for that of SMV. The evaluation includes collagen deposition, inflammatory responses, antimicrobial assays, and in-vivo wound healing process. The PPCS hydrogels demonstrate adequate pH sensitivity within the range of 5.6 to 7.4, desirable mechanical properties, optimal adhesive strength, and appropriate degradation rate, all dependent on environmental pH. Notably, a decrease in pH is found to result in an increase in cumulative drug release (similar to 2 times), with SMV demonstrating controlled release but CIP exhibiting rapid release. This tunable drug delivery platform markedly enhances the proliferation of skin cells, as demonstrated by approximately a twofold increase in collagen I production, modulation of pro-inflammatory cytokines, elevation of anti-inflammatory cytokines, and suppression of bacterial proliferation. In a full-thickness skin wound rat model, the PGS/P beta AE-CIP/SMV (PPCS) hydrogel facilitated wound closure by nearly 85 within 14 days post-operation, in contrast to about 60 in the untreated control. The multifunctional PPCS hydrogel developed in this study, due to its targeted immunomodulatory characteristics and antibacterial effects, demonstrates significant potential for promoting enhanced and accelerated skin regeneration in full-thickness wounds.