On-Demand Dissolvable Self-Healing Hydrogel Based on Carboxymethyl Chitosan and Cellulose Nanocrystal for Deep Partial Thickness Burn Wound Healing

Abstract

Deep partial thickness burn wounds present big challenges due to the long healing time, large size and irregular shape, pain and reinjury at wound dressing changes, as well as scarring. The clinically effective therapy to alleviate pain at wound dressing changes, and the scar left on the skin after the healing of wound is still unavailable. To combat this, we develop a nanocomposite self-healing hydrogel that can be injected into irregular and deep burn wound beds and subsequently rapidly self-heal to reform into an integrated piece of hydrogel that thoroughly fills the wound area and protects the wound site from external environment, finally being painlessly removed by on-demand dissolving using amino acid solution at wound dressing changes, which accelerates deep partial thickness burn wound healing and prevents scarring. The hydrogel is made out of naturally occurring polymers, namely, water-soluble carboxymethyl chitosan (CMC) and rigid rod-like dialdehyde-modified cellulose nanocrystal (DACNC). They are cross-linked by dynamic Schiff-base linkages between amines from CMC and aldehydes from DACNC. The large aspect ratio and specific surface area of DACNC raise massive active junctions within the hydrogel, which can be readily broken and reformed, allowing hydrogel to rapidly self-heal. Moreover, DACNC serves as nanoreinforcing fillers to improve the hydrogel strength, which also restricts the "soft" CMC chains' motion when soaked in aqueous system, endowing high fluid uptake capacity (350%) to hydrogel while maintaining integrity. Cytotoxicity assay and three-dimensional cell culture demonstrate excellent biocompatibility of the hydrogel and capacity as extracellular matrix to support cell growth. This work opens a novel pathway to fabricate on-demand dissolvable self-healing hydrogels to speed deep partial thickness burn wound healing and eliminate pain at wound dressing changes and prevent scar formation.