Modulating cationicity of chitosan hydrogel to prevent hypertrophic scar formation during wound healing

It is of great clinical significance to design wound dressing materials with combined excellent wound healing properties and superior capability to suppress hypertrophic scar formation. This study aimed to examine if and how the cationicity of chitosan would affect the hypertrophic scar-related outcomes, through preparing carboxymethyl chitosan hydrogels with different genipin concentrations (2.5%, 5%, 10% and 15%, respectively). An optimum window of chitosan cationicity (5% in our case) demonstrated potential to mitigate hypertrophic scar in wound healing by suppressing the expression of a-smooth muscle actin (a-SMA) and promoting secretion of type I matrix metalloproteinases (MMP-1). In vivo, the CMCS-5% hydrogel again showed smaller, thinner and smoother wound appearance. Moreover, the CMCS-5% sample with additional incorporation of 2% (V/V) Aloe vera gel exhibited further improved performance in scar inhibition. Overall, such findings might have important implications in chitosan-based wound dressing design for high-quality wound repair and effective scar inhibition. •Chitosan cationicity was modulated with different concentrations of genipin.•Cationicity of chitosan hydrogels affected expression levels of a-SMA and MMP-1.•Chitosan-5% hydrogel showed the best prevention effect for hypertrophic scar.•Co-treatment with CMCS-5% and Aloe vera gel further improved wound appearance.