Fumaric acid incorporated Ag/agar-agar hybrid hydrogel: A multifunctional avenue to tackle wound healing

Wound and its treatment is one of the major health concerns throughout the globe. Various extrinsic and intrinsic factors can influence the dynamics of healing mechanism. One such extrinsic factor is moist environment in wound healing. The advantages of optimum hydration in wound healing are enhanced autolytic debridement, angiogenesis and accelerated cell proliferation and collagen formation. But hydrated wounds often end up with patient's uncomfortability, associated infection, and tissue lipid peroxidation. Healing process prefers antimicrobial, anti-inflammatory and optimum moist microenvironment. Here, we have synthesized fumaric acid incorporated agar-silver hydrogel (AA-Ag-FA); characterized by UV-Visible spectroscopy, FTIR spectroscopy and TEM. The surface morphology is evaluated through SEM. The size of the silver nanoparticles (Ag NPs) was found to be 10-15 nm. The hydrogel shows potential antibacterial effect against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa which are predominantly responsible for wound infection. The gel shows reasonable antioxidant property evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Topical application of the gel on the wound site heals the wound at much faster rate even compared to standard (Mega heal, Composition: Colloidal silver 32 ppm hydrogel) gel. Histological analysis reveals better tissue proliferation (i.e. epithelialization), more granulation tissue formation, neovascularisation, fibroblast and mature collagen bundles. The lipid peroxidation of wound tissue estimated through malondialdehyde (MDA) assay was found to be reasonably less when treated with AA-Ag-FA hydrogel compared to standard (Mega heal). Cytotoxicity of the samples tested through MTT assay and live-dead cell staining shows its nontoxic biocompatibility nature. In our hydrogel scaffold, the bio-degradable agar-agar provides the moist environment; the Ag NPs inside the gel acts as bactericidal agent and fumaric acid facilities the antioxidant and angiogenesis path implicitly.