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.

Bioinspired Double‐Dynamic‐Bond Crosslinked Bioadhesive Enables Post‐Wound Closure Care

“…For example, after a wound is closed, it may need further handling, such as changing or adding medicines, according to the state of healing, which requires painlessly changing or removing the applied bioadhesives. [ 11,12 ] In addition, the closed wounds, especially those closed skin wounds, may be reopened during the post‐wound closure time, as shown by a clinical study which reported that about 26% of the groin skin wounds that were closed by bioadhesives were dehiscent and these reopened wounds require repeated closure to prevent the risk of infection and delayed healing. [ 13 ] Accordingly, developing a versatile bioadhesive that is capable of efficiently closing open wounds and enabling post‐wound closure care is imperative.…”

Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose

“…Huang et al described an injectable hydrogel prepared using carboxymethylchitosan and dialdehyde modified CNCs. 174 The gel demonstrated very good biocompatibility, self-healing and on-demand solubilisation under mildly acidic conditions. The gel was tested as a wound-healing agent in a deep partial thickness skin burn model in vivo and was shown to be effective for burn surface covering and treatment.…”

Recent Progress of Polysaccharide‐Based Hydrogel Interfaces for Wound Healing and Tissue Engineering

“…In view of this issue, Zhang and coworkers developed self‐healing hydrogel nanocomposites, which were made of carboxymethyl chitosan and cellulose nanocrystals. It can be injected into burn wounds to fully cover the wound sites, followed by rapidly transferring into an integrated hydrogel that thoroughly filled the wound region and isolated the wound site from external environment, and finally painlessly removed by dissolving with amino acid solution . Besides, Zhao and coworkers proposed a hybrid hydrogel consisted of a benzaldehyde‐terminated polyethylene glycol and dodecyl‐modified chitosan.…”