Treatment of severe burn wound injury remains a significant clinical challenge as serious infections/complex repair process and irregulating inflammation response. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have a multidirectional differentiation potential and could repair multiple injuries under appropriate conditions. Poly(L-lysine)-graft-4-hydroxyphenylacetic acid (PLL-g-HPA) hydrogel is an enzyme-promoted biodegradable in hydrogel with good water absorption, biocompatibility and anti-bacterial properties. Therefore, the aim of this study was to evaluate the therapeutic effect of hUC-MSCs combined with PLL-g-HPA hydrogel on full thickness burn injury in rat model. The PLL-g-HPA hydrogel was developed and characterized by Scanning Electron Microscopy (SEM), Fourier-Transform Infrared Spectroscopy (FTIR), Hydrogen-1 nuclear magnetic resonance (H-NMR). The cytotoxicity to human foreskin fibroblasts (HFF) were assessed by CCK-8 assay and live/dead quantification and antibacterial activity against Escherichia coli and Staphylococcus aureus was also detected by colony forming unit. A full-thickness burn wound injury model in 12 SD rats was established, and the therapeutic effect of PLL-g-HPA hydrogel combined with hUC-MSCs was detected by healing time/Histology/inflammation factor expression level. The findings from SEM, FTIR, and HFF analyses demonstrated the successful synthesis of PLL-g-HPA hydrogels. These hydrogels exhibited low cytotoxicity at minimal concentrations while maintaining excellent moisture retention and antibacterial properties. Compared to the control group, treatment with PLL-g-HPA hydrogel in conjunction with hUC-MSCs significantly enhanced wound healing, modulated inflammatory responses, and promoted angiogenesis as well as re-epithelialization in rat models. The PLL-g-HPA hydrogel in conjunction with hUC-MSCs represents a promising therapeutic approach for the management of burn wounds.
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