Silk-based phyto-hydrogel formulation expedites key events of wound healing in full-thickness skin defect model

Immense socio-economic burden of chronic wound demands effective, low-cost strategies for wound care. Herein, we have developed a chemical crosslinker-free phyto-hydrogel by encapsulating phytochemicals of Aloe vera mucilage extract (AVM) in the self-assembled polymeric chains of two different silk fibroin (SF) proteins (from Bombyx mori and Antheraea assamensis). Additionally, polyvinylpyrrolidone (PVP) has been used as a stabilizer that also contributed to the mucoadhesive property of the composite (SAP; made of SF, AVM, and PVP) hydrogel. The physicochemical properties of the hydrogel were evaluated and compared with SF hydrogel containing only SF proteins without any additives. The biocompatibility assessment of the hydrogel under in vitro conditions has shown improved cellular proliferative and migratory responses, suggesting faster tissue repairability of the hydrogel. A detailed in vivo comparative study with a commercially available DuoDERM® gel revealed that SAP hydrogel not only promoted wound closure but also showed better deposition and remodeling of the extracellular matrix. Moreover, the hydrogel also demonstrated its ability to downregulate pro-inflammatory markers (IL-1β, TNF-α) and upregulation of anti-inflammatory markers (IL-10, TGF-β) at the early stage of healing. Therefore, the bioactive proteins-carbohydrates composite efficiently accelerates skin regeneration and possesses great translational potential to offer a low-cost alternative wound care therapeutic.