Chronic diabetic wounds are a major complication of diabetes mellitus and are characterised by delayed and impaired healing caused by neuropathy, vascular dysfunction, and persistent infection. Human amniotic membrane derivative (hAMD) has emerged as a promising biomaterial for wound management due to its anti-inflammatory properties and rich content of growth factors. This study aimed to evaluate the feasibility, efficacy, and safety of an hAMD-based hydrogel as a wound dressing under hyperglycemic conditions. An in vivo experimental study was conducted in alloxan-induced diabetic mice treated with various hydrogel formulations, including a carbopol hydrogel, a commercial hydrogel, and an hAMD-based hydrogel. Wound healing was assessed through macroscopic evaluation of wound closure. Safety and biocompatibility were evaluated based on physicochemical properties (organoleptic characteristics, pH, and viscosity), mechanical performance (tensile strength), microbiological testing, and systemic toxicity assessment. Haematological parameters (haemoglobin and leukocyte counts) and biochemical markers of kidney and liver function, including urea, creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), were also analysed. The results showed that the hAMD-based hydrogel achieved significantly faster wound closure, approximately 20% faster than the diabetic control group and 10–15% faster than the healthy control, carbopol-treated, and commercial hydrogel groups. The hAMD-based hydrogel demonstrated a favourable safety profile, with no evidence of systemic toxicity or organ dysfunction. It also met acceptable standards for physicochemical stability, mechanical integrity, microbiological safety, and physiological compatibility. In conclusion, the hAMD-based hydrogel shows strong potential as a safe and effective wound dressing for diabetic ulcers, supporting its further development for clinical wound care applications.
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