Synthesis, Characterization, and Implantation of Ferulic Acid-Loaded Chitosan/Aloe vera Hydrogels in Rat Full-Thickness Wound Model.

Chronic wounds are clinical challenges characterized by delayed healing and persistent inflammation. Tissue engineering offers novel strategies to enhance skin regeneration and restore tissue homeostasis. In the present study, we fabricated FA-loaded Cs/Av hydrogel scaffolds and evaluated their effect on wound healing in a full-thickness wound model in rats. A temperature-sensitive chitosan/Aloe vera (Av, 1%, 2%, 4% w/v) hydrogel was prepared and loaded with ferulic acid (FA, 50 μM). The physicochemical characteristics of hydrogels were evaluated using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), water absorption, degradation, and antibacterial activity assessments. Wound closure and histopathological demonstrations were assessed in a rat full-thickness wound model on Days 5, 10, and 14. SEM analysis revealed that scaffolds were highly porous with interconnected pores ranging from 110 to 180 μm. FTIR data confirmed the incorporation of FA and Av. Water uptake, degradation rate, and antibacterial activity increased proportionally to Av concentration, reaching 519%, 48%, and 30.66 mm, respectively, in FA-Cs/Av 4% scaffolds. Wound closure was accelerated by 67% and 91% on Days 10 and 14 in FA-Cs/Av 4% hydrogel. Histological assessments showed that implanted scaffolds improved skin regeneration by reducing inflammation and enhancing angiogenesis, collagen deposition, and re-epithelialization in treated groups. FA-Cs/Av scaffolds provide a multifunctional platform for repairing chronic wounds, with excellent antioxidant, anti-inflammatory, and antibacterial effects, and controlled hydration and degradation, which could be considered for therapeutic purposes in the future.