Hyaluronic acid-tannic acid hydrogel incorporating berberine nanoliposomes enhances infected wound healing.

Infected wounds remain a major clinical challenge due to persistent inflammation, microbial colonization, and increasing antibiotic resistance. Here, we developed an injectable hyaluronic acid (HA)-tannic acid (TA) hydrogel incorporating berberine-loaded nanoliposomes (BRB-NLPs) as a multifunctional therapeutic platform. The hydrogel was prepared via PEGDE-mediated crosslinking and subsequent TA functionalization, followed by uniform embedding of BRB-NLPs. Physicochemical analyses confirmed successful crosslinking, thermal stability, tunable swelling, and a porous morphology suitable for drug loading. The system achieved high berberine encapsulation efficiency (87 %) and sustained release while maintaining nanoparticle stability. In vitro studies demonstrated strong antibacterial activity and excellent cytocompatibility. In a murine excision-infected wound model, HA/TA/BRB-NLPs significantly accelerated wound closure, promoted re-epithelialization and collagen deposition, and reduced bacterial burden. Molecular assays further revealed downregulation of pro-inflammatory mediators (IL-1β, TNF-α, TIMP-1/2, MMP-9) alongside upregulation of regenerative and anti-inflammatory markers (TGF-β, IL-10, COL1A1). Collectively, these findings highlight HA/TA/BRB-NLP hydrogels as a promising antibiotic-free biointerface material with synergistic antibacterial, anti-inflammatory, and regenerative effects for the management of infected wounds.