Nitric oxide-releasing multifunctional catechol-modified chitosan/oxidized dextran hydrogel with antibacterial, antioxidant, and pro-angiogenic properties for MRSA-infected diabetic wound healing

Int J Biol Macromol. 2024 Apr;263(Pt 1):130225. doi: 10.1016/j.ijbiomac.2024.130225. Epub 2024 Feb 17.

Abstract

The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves ∼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, •OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.

Keywords: Antibacterial activity; Antioxidant property; Catechol-modified chitosan; Hydrogel; Pro-angiogenesis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antioxidants / pharmacology
  • Catechols
  • Chitosan*
  • Dextrans
  • Diabetes Mellitus*
  • Hydrogels / pharmacology
  • Methicillin-Resistant Staphylococcus aureus*
  • Nitric Oxide
  • Wound Healing

Substances

  • Antioxidants
  • Nitric Oxide
  • Hydrogels
  • Chitosan
  • Dextrans
  • catechol
  • Catechols
  • Anti-Bacterial Agents