pH-responsive and self-adaptive hydrogel dressing based on a TA/PVA network co-loaded with cannabidiol and mupirocin for synergistic infected wound healing

  • Phytomedicine. 2026 May:154:158043. doi: 10.1016/j.phymed.2026.158043.
Guanjun Ye  1 ,  Jiangfei Li  2 ,  Heqi Gao  1 ,  Zhilong Zhou  2 ,  Mengnan Liu  3 ,  Linjie Li  4 ,  Alejandro Cifuentes  5 ,  Yingchun Zhang  6 ,  Weihong Lu  7
Affiliations
  • 1. Department of Food Nutrition and Health, School of Medicine and Health, Faculty of Life Sciences and Medicine, Harbin Institute of Technology, Harbin 150001, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China.
  • 2. Department of Food Nutrition and Health, School of Medicine and Health, Faculty of Life Sciences and Medicine, Harbin Institute of Technology, Harbin 150001, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou 450003, China.
  • 3. National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou 450003, China.
  • 4. National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China.
  • 5. Laboratory of Foodomics, Institute of Food Science Research (CIAL-CSIC), Nicolás Cabrera 9, Madrid 28049, Spain.
  • 6. Department of Food Nutrition and Health, School of Medicine and Health, Faculty of Life Sciences and Medicine, Harbin Institute of Technology, Harbin 150001, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China. Electronic address: [email protected].
  • 7. Department of Food Nutrition and Health, School of Medicine and Health, Faculty of Life Sciences and Medicine, Harbin Institute of Technology, Harbin 150001, China; National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental Nutrients, Harbin Institute of Technology, Harbin 150001, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou 450003, China. Electronic address: [email protected].
PMID: 41831383 DOI: 10.1016/j.phymed.2026.158043
Abstract

Background: The development of advanced wound dressings capable of dynamically adapting to the complex wound microenvironment represents a critical unmet need in the management of infected and chronic wounds.

Methods: A novel multifunctional hydrogel dressing was fabricated through a green, physical crosslinking strategy based on hydrogen bonding between tannic acid (TA) and polyvinyl alcohol (PVA). The network was co-loaded with cannabidiol (CBD) and mupirocin (MUP) to achieve synergistic therapeutic effects. The hydrogel was characterized for its microstructure, mechanical properties, swelling capacity, and pH-responsive behavior. In vitro evaluations included Antibacterial activity, antioxidant capacity, biocompatibility, and fibroblast migration assays. In vivo efficacy was assessed using a murine full-thickness wound model.

Results: The optimized hydrogel exhibited a uniform porous structure, suitable mechanical properties, and excellent swelling capacity. It demonstrated intelligent pH-responsive degradation and drug release, with accelerated release under alkaline conditions and sustained release under acidic conditions. In vitro, the hydrogel showed potent broad-spectrum Antibacterial activity, pH-modulated antioxidant capacity, excellent biocompatibility, and promoted fibroblast migration. In vivo, it significantly accelerated wound closure (72.80 % by day 7) and enhanced tissue regeneration through improved re-epithelialization, Collagen deposition, and angiogenesis, with histopathological analysis confirming excellent biosafety.

Conclusions: This study provides an innovative, responsive hydrogel platform that intelligently coordinates Antibacterial, antioxidant, and pro-healing functions. The work offers a promising strategy for managing infected and chronic wounds through a dynamically adaptive and synergistic therapeutic approach.

Keywords
Cannabidiol; Hydrogel dressing; Synergistic therapy; Tannic acid; pH-responsive.
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