Abstract
Diabetic wounds are characterized by persistent oxidative stress, low-grade inflammation, and impaired matrix remodelling, which culminate in delayed closure and high rates of infection, amputation, and mortality. Redox-active nanomaterials such as cerium oxide and gold nanoparticles offer a rational strategy to intercept reactive oxygen species and rebalance pro- and anti-inflammatory signalling at the wound interface. This preclinical study evaluated a topically applied gold–cerium oxide (Au–CeO₂) nanocomposite hydrogel as an adjunctive therapy for cutaneous wound repair in streptozotocin-induced diabetic rats. After induction and stabilization of diabetes, standardized full-thickness dorsal excisional wounds were created and animals were randomized to receive either a nanoparticle-free hydrogel base or the Au–CeO₂ nanocomposite hydrogel once daily for up to 21 days. Macroscopic wound contraction and time to complete epithelialization were quantified from serial planimetric measurements. At predefined endpoints, wound tissue was harvested to assess oxidative stress (malondialdehyde, reduced glutathione, and antioxidant enzymes), inflammatory cytokines (TNF-α, IL-1β, IL-6), pro-healing mediators (VEGF, TGF-β1), and matrix remodelling markers (MMP-9, TIMP-1, hydroxyproline). Systemic oxidative stress indices, circulating cytokines, routine clinical chemistry, and haematological parameters were also measured, and a subset of rats underwent biomechanical testing of healed skin. Data were summarized as mean ± SD and compared between groups using Welch’s unequal-variance independent-samples t-test. Au–CeO₂ hydrogel treatment significantly accelerated wound contraction at all time points and shortened epithelialization by nearly four days relative to the hydrogel base (p < 0.001). Treated wounds showed lower lipid peroxidation and pro-inflammatory cytokines, higher antioxidant capacity and pro-angiogenic growth factors, a more favourable MMP-9/TIMP-1 profile with increased hydroxyproline, and superior mechanical strength of the repair tissue, without evidence of systemic toxicity. These findings support Au–CeO₂ nanocomposite hydrogel as a promising redox-modulating platform for enhancing diabetic wound healing. Further dose optimization, mechanistic exploration, and comparative studies against established advanced dressings are warranted in diabetic models.