Wound Healing Potential of Aloe Vera Gel versus Antibiotic in Silk Fibroin/Gelatin-Based Fibrous Wound Dressings: Insights from In Vitro, In Vivo, and Computational Studies

Nanofibrous scaffolds have been proposed as suitable wound dressings due to their structural similarity to the extracellular matrix, high biocompatibility, and ability to load therapeutic agents. In this study, a bilayer scaffold was fabricated in which the top layer is composed of silk fibroin acting as a protective coating and providing mechanical strength, while the bottom layer was composed of gelatin containing ciprofloxacin or Aloe vera gel powder to directly contact the wound bed. The physical, chemical, and biological properties of the scaffolds were evaluated using SEM, FTIR, swelling, degradation, cell adhesion, and MTT tests. In addition, computational molecular docking was utilized to investigate the molecular interactions between the active compounds (aloin and ciprofloxacin) and essential proteins involved in the inflammatory, proliferative, and regenerative stages of wound healing. Furthermore, a full-thickness skin wound model in rats was established to assess the in vivo healing process. SEM images showed uniform fibers and a porous structure. MTT assay confirmed favorable biocompatibility. Moreover, appropriate swelling behavior and controlled degradation provided a moist and stable environment for wound healing. Molecular docking studies showed that aloin, the main active compound of Aloe vera, exhibited strong interactions with key proteins of the inflammatory and regeneration phases and was able to inhibit inflammatory pathways and stimulate angiogenesis and matrix remodeling processes. In contrast, ciprofloxacin showed weaker regenerative potential. Histological results indicated a decrease in inflammation, along with an increase in fibroblast number, angiogenesis, and collagen synthesis and organization in the Aloe vera group particularly at the 10% concentration. Overall, the scaffolds containing Aloe vera, while maintaining appropriate physical properties and biocompatibility, also activated anti-inflammatory and regenerative pathways and accelerated the wound healing process.