Evaluation of the effects of alpha-lipoic acid, vitamin C and nanomaterials on the healing of full-thickness skin wounds in a rat model

In this study, the effects of topically applied alpha-lipoic acid (ALA) and its nanoparticle-encapsulated formulations on the healing of full-thickness skin wounds were evaluated using histopathological, immunohistochemical, and biochemical parameters, and compared with a vitamin C-treated group. A wound is defined as the loss of anatomical and functional integrity of living tissue. ALA is known to contribute positively to wound healing by supporting anti-inflammatory, antimicrobial, and cellular antioxidant mechanisms. Therefore, the potential effects of ALA and its nanoencapsulated forms on wound healing were investigated. Forty male Wistar albino rats, 16 weeks of age, were used in the study. Under anesthesia, a full-thickness skin wound with a diameter of 1 cm was created on the dorsal region of each animal. The rats were then divided into five groups, each consisting of eight animals. These included a control group with no treatment, a vitamin C group receiving 1000 mg/kg/day of vitamin C by gastric gavage, an ALA group receiving 10 mg/kg/day of topical ALA, a nanoparticle-ALA (NPsALA) group receiving 10 mg/kg/day of ALA in nanoparticle form, and a NPsAgFeALA group treated topically with 10 mg/kg/day of ALA encapsulated in silver-iron nanoparticles. The experiment continued for eleven days. At the end of the study, tissue samples containing the wound area and surrounding healthy skin were collected and examined histopathologically using hematoxylin-eosin (H&E) and Masson's trichrome staining, and immunohistochemically for TNF-alpha and type III collagen (COL3). In addition, blood samples were analyzed for biochemical markers of oxidative stress and antioxidant activity, including catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological and immunohistochemical analyses showed that ALA and its nanoparticle forms accelerated wound healing, increased collagen synthesis, and supported re-epithelialization. Blood analysis revealed that enzymatic antioxidant levels (CAT and SOD) were higher in the NPsALA group compared to the control and ALA only groups, indicating that the nanoparticle formulation had a stronger systemic antioxidant effect. In conclusion, ALA and its nanoparticle-based formulations were found to contribute positively to the wound healing process by enhancing fibroblast activity and vascular proliferation, thus supporting tissue remodeling in a full-thickness wound model in rats.