Studies of Mercaptosuccinic Acid-Crosslinked Chitosan Hydrogel with Grafted Cinnamaldehyde and Silver Nanoparticles for Antibacterial Biomedical Application

Int J Mol Sci. 2022 Nov 26;23(23):14806. doi: 10.3390/ijms232314806.


For the effective clinical antibacterial application of biomaterials, such as for wound management and tissue repair, the biomaterials need to show proper antibacterial capability as well as non-cytotoxicity. Furthermore, the material needs to have suitable mechanical characteristics for further medical use. Chitosan hydrogel is a potential candidate for various antibacterial biomedical applications due to its amine functionalities that lead to antimicrobial characteristics. Nevertheless, its antimicrobial capability is dependent upon the degree of protonation of amine groups caused by the pH value. Moreover, its mechanical compressive strength may not be high enough for clinical use if not chemically or physically crosslinked. This study utilized a novel chemical crosslinker, mercaptosuccinic acid, to improve its mechanical characteristics. The natural antibacterial agent, cinnamaldehyde, was grafted onto the crosslinked chitosan to improve its antimicrobial capability. Meanwhile, to take advantage of the thiol functionality in the mercaptosuccinic acid, the bactericidal silver nanoparticles were incorporated through silver-thiol covalent bounding. NMR analyses indicated the chitosan was successfully mercaptosuccinic acid-crosslinked and grafted with cinnamaldehyde at different ratios. Combined the results from the mechanical assessment, swelling experiments, antimicrobial assessment, and cytotoxicity assay, the chitosan hydrogel with the highest crosslinked degree and grafted with cinnamaldehyde and silver nanoparticles is of great promise for further clinical uses.

Keywords: antimicrobial properties; chemical crosslinking; chitosan; cinnamaldehyde; cytotoxicity.

MeSH terms

  • Amines
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Chitosan* / chemistry
  • Hydrogels / chemistry
  • Metal Nanoparticles* / chemistry
  • Silver / chemistry
  • Thiomalates


  • Chitosan
  • Hydrogels
  • Silver
  • 2-thiomalic acid
  • Anti-Bacterial Agents
  • Thiomalates
  • cinnamaldehyde
  • Amines