Enhancing Photothermal Therapy for Antibiofilm Wound Healing: Insights from Graphene Oxide-Cranberry Nanosheet Loaded Hydrogel in vitro, in silico, and in vivo Evaluation

Int J Nanomedicine. 2024 Dec 3:19:12999-13027. doi: 10.2147/IJN.S482836. eCollection 2024.

Abstract

Background: Diabetic foot ulcers present a formidable challenge due to colonization by biofilm-forming microorganisms, heightened oxidative stress, and continuous wound maceration caused by excessive exudation.

Methods: To address these issues, we developed a robust, stretchable, electro-conductive, self-healing, antioxidant, and antibiofilm hydrogel. This hydrogel was synthesized through the crosslinking of polyvinyl alcohol (PVA) and chitosan (CH) with boric acid. To enhance its antimicrobial efficacy, graphene oxide (GO), produced via electrochemical exfoliation in a zinc ion-based electrolyte medium, was incorporated. For optimal antibiofilm performance, GO was functionalized with cranberry (CR) phenolic extracts, forming a graphene oxide-cranberry nanohybrid (GO-CR).

Results: The incorporation of GO-CR into the hydrogel significantly improved its stretchability (280% for PVA/CH/GO-CR compared to 200% for PVA/CH). Additionally, the hydrogel demonstrated efficient photothermal conversion under near-infrared (NIR) light, enabling dynamic exudate removal, which is expected to minimize retained exudate between the wound and the dressing, reducing the risk of wound maceration. The hydrogel effectively reduced levels of lipopolysaccharide (LPS)-induced skin inflammation markers, significantly lowering the expression of NLRP3, TNF-α, IL-6, and IL-1β by 39.2%, 31.9%, 41%, and 52.3%, respectively. Histopathological and immunohistochemical analyses further confirmed reduced inflammation and enhanced wound healing.

Conclusion: The PVA/CH/GO-CR hydrogel exhibits multifunctional properties that enhance wound healing ulcers. Its superior mechanical, antibacterial, and anti-inflammatory properties and ability to promote angiogenesis make it a promising candidate for effective wound management in diabetic patients.

Keywords: antibiofilm; cranberry extract; electro conductive hydrogel; graphene oxide; nanocomposite; photothermal conversion; self-healing; wound healing.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biofilms* / drug effects
  • Chitosan / chemistry
  • Chitosan / pharmacology
  • Computer Simulation
  • Diabetic Foot / drug therapy
  • Diabetic Foot / therapy
  • Graphite* / chemistry
  • Graphite* / pharmacology
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Male
  • Mice
  • Nanostructures / chemistry
  • Photothermal Therapy* / methods
  • Polyvinyl Alcohol / chemistry
  • Polyvinyl Alcohol / pharmacology
  • Wound Healing* / drug effects

Substances

  • Graphite
  • graphene oxide
  • Hydrogels
  • Anti-Bacterial Agents
  • Polyvinyl Alcohol
  • Chitosan

Grants and funding

This work was partially funded by the University of Sharjah for AA.