Photocrosslinkable Morin-loaded gelatin-g-GMA composite hydrogel for accelerating burn wound healing: in vitro and in vivo assessments

Abstract

The impaired skin regeneration, scarring, and delayed healing make the management of burn injuries a challenging task. We designed a photopolymerized hydrogel of gelatin-grafted with glycidyl methacrylate (GMA) for burn management applications. Hydrogel was incorporated with Morin, a plant flavonoid that was originally isolated from the Moraceae family, with known anti-antioxidant and anti-fibrotic activities. The physicochemical characterization of the resultant hydrogel, including its gelation time and swelling properties, was conducted. The characterization results indicated that the hydrogel development was successful, exhibiting well-established porosity, as evidenced by the SEM images. In vivo evaluation demonstrated improved tissue regeneration characterized by enhanced collagen deposition and dermal re-modelling. Additionally, histopathological analysis indicated reduced fibrotic features and accelerated wound closure. Moreover, the hydrogel promoted epithelial regeneration, accelerating the closure of burns in a burn rat model. Furthermore, in vitro studies using a THP-1-derived M1 macrophage model, showed that the Morin-loaded hydrogel formulations GH-5, GH-6, and GH-7 demonstrated a potent, concentration-dependent suppression of key M1 inflammatory mediators including nitric oxide (NO), IL-1β, and IL-6. This anti-inflammatory effect was mechanistically linked to the downregulation of critical genes (iNOS, COX-2, and STAT-3) that drive the M1 phenotype. Notably, the hydrogel with the highest Morin concentration (GH-7, 5%) exhibited the most significant reduction in inflammatory outputs, suggesting that the therapeutic efficacy is enhanced by Morin loading onto nanofibers. Collectively, this study provides a foundation for the development of functional hydrogels in regenerative medicine and tissue engineering, particularly in relation to burn therapy and modulating macrophage-driven inflammatory pathologies.