pH-Responsive Bilayer Hydrogel with Synergistic Antibacterial/Anti-inflammatory Effect for Infected Wound Healing
Mengxin Huangfu, Yuankun Ren, Wei Yang, Ying Liu, Xiyu Li
Abstract
Hydrogels are promising candidates for wound dressings owing to their good biocompatibility, high-water retention, and extracellular matrix-mimicking structure. However, conventional single-layer hydrogels are hard to cope with given the dynamic pH fluctuations (pH 6–8.9) of infected wounds, which exacerbate bacterial colonization and oxidative stress. Here, we engineered a multifunctional bilayer hydrogel (named PPTC) comprising a hydrophobic polydimethylsiloxane (PDMS) top layer and a polyacrylamide (PAM)-based bottom layer integrated with tannic acid (TA) and curcumin-loaded alginate microspheres (Alg@Cur). The PDMS top layer was adopted to prevent external contamination and moisture loss, while the adhesive PAM-TA-Alg@Cur (PTC) bottom layer was designed to achieve a pH-responsive therapeutic synergy. In vitro studies showed that TA exhibited a rapid release (76.66% within 12 h) to suppress bacterial proliferation and inflammation, while Alg@Cur could slowly release curcumin in a pH-dependent manner (90.32% at pH 8.5 vs 38.06% at pH 6, cumulatively), targeting alkaline microenvironments to mitigate oxidative stress. Their synergy demonstrated potent antibacterial activity (≥99.90% inhibition against Staphylococcus aureus and Escherichia coli ) and reactive oxygen species scavenging ability (93.89% DPPH elimination). In a rat-infected wound model, the PPTC bilayer hydrogel synergistically accelerated infected wound healing by reducing inflammation, enhancing collagen deposition, and promoting angiogenesis. This work pioneers a pH-driven therapeutic platform for advancing smart dressings for infected wound management.