Thermogelling chitosan-based polymers for the treatment of oral mucosa ulcers

Biomater Sci. 2020 Mar 7;8(5):1364-1379. doi: 10.1039/c9bm01754b. Epub 2020 Jan 9.

Abstract

Current treatments for oral mucosa-related ulcers use drugs to relieve pain and promote healing, but rarely consider drug resistance to bacterial infection in the microenvironment of the oral cavity or the prevention of bleeding from gingival mucosa ulcers. We herein report an injectable, thermogelling chitosan-based system to address these concerns. An aqueous solution of chitosan-based conjugates (chitosan-g-poly(N-isopropylacrylamide) [CS-g-PNIPAAM] including 1a [CS-g-PNIPAAM with less PNIPAAM] and 1b [CS-g-PNIPAAM with more PNIPAAM], and chitosan-g-poly(N-isopropylacrylamide)-g-polyacrylamide [CS-g-PNIPAAM-g-PAM] 3) could reversibly form semi-solid gels at physiological temperatures for easy application to oral cavity ulcer sites by injection. The chitosan-based conjugate thermogels prepared could inhibit both Gram-positive and Gram-negative bacteria and the two with higher chitosan and poly(N-isopropylacrylamide) contents (1a and 1b) promoted proliferation of gingival fibroblasts in vitro. These two thermogels also exhibited improved blood clotting in an in vivo rat study. Thermogels 1a and 1b effectively promoted ulcer healing and shortened ulcer healing times in an oral gingival mucosa ulcer model using Sprague Dawley (SD) rats. These thermogels showed no obvious toxicity to the main organs of SD rats undergoing gingival ulcer treatment. These results suggest that this antibacterial biomaterial could be a promising injectable therapeutic agent for the treatment for oral mucosa ulcers.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Ulcer Agents / chemical synthesis
  • Anti-Ulcer Agents / chemistry
  • Anti-Ulcer Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Escherichia coli / drug effects
  • Gels / chemical synthesis
  • Gels / chemistry
  • Gels / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Mouth Mucosa / drug effects*
  • Mouth Mucosa / pathology
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Staphylococcus aureus / drug effects
  • Temperature
  • Ulcer / drug therapy*
  • Ulcer / pathology

Substances

  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Gels
  • Polymers
  • Chitosan