A novel TCR hydrogel wound dressing loaded with UC-SMC extract enhances skin regeneration and prevents wound scarring

Tissue fibrosis and scar formation are inevitable parts of wound healing in adult mammals, leading to a range of adverse outcomes including physical disability and psychological problems. In which, infiammation network plays a crucial role in this pathological process. Novel wound dressing materials with ideal biocompatibility, morphology adaptability, adequate mechanical strength, considerable wet-surface adhesion, and active drug delivery properties are urgently needed for clinical applications. In this study, umbilical cord mesenchymal stem cell extract (UC-SCE) was developed and verified for its ability to inhibit wound infiammation by driving macrophage polarization towards the anti-infiammatory (M2) phenotype and to promote wound tissue regen-eration in SD rat wound model. Meanwhile, UC-SCE has also been shown to inhibit dermal fibroblast prolifer-ation, migration and matrix production, and also to inhibit angiogenesis both in vitro and in vivo, and thus proving its anti-scarring capability. Furthermore, a novel dynamic-to-covalent hydrogel based on tandem crosslinking reaction (TCR) has been developed as a drug carrier for US-SCE delivery, which demonstrated suitable injectability, proper mechanical stability and excellent tissue adhesion. More importantly, when loaded with UC-SCE, this novel wound dressing was demonstrated able to regenerate wound tissue and inhibit hyper-trophic scar formation in a rabbit ear scar model, thus principally proved the feasibility, efficacy and applica-bility of this novel SCE-hydrogel wound dressing for potential clinical translation.