Beneficial Effects of a Blended Fibroin/Aloe Gel Extract Film on the Biomolecular Mechanism(s) via the MAPK/ERK Pathway Relating to Diabetic Wound Healing

[Image: see text] In diabetic patients, the process of wound healing is usually delayed or impaired. A diabetic environment could be associated with dermal fibroblast dysfunction, reduced angiogenesis, the release of excessive proinflammatory cytokines, and senescence features. Alternative therapeutic treatments using natural products are highly demanded for their high potential of bioactive activity in skin repair. Two natural extracts were combined to develop fibroin/aloe gel wound dressing. Our previous studies revealed that the prepared film enhances the healing rate of diabetic foot ulcers (DFUs). Moreover, we aimed to explore its biological effects and underlying biomolecular mechanisms on normal dermal, diabetic dermal, and diabetic wound fibroblasts. Cell culture experiments showed that the γ-irradiated blended fibroin/aloe gel extract film promotes skin wound healing by enhancing cell proliferation and migration, vascular epidermal growth factor (VEGF) secretion, and cell senescence prevention. Its action was mainly linked to the activation of the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway known to regulate various cellular activities, including proliferation. Therefore, the findings of this study confirm and support our previous data. The blended fibroin/aloe gel extract film displays a biological behavior with favorable properties for delayed wound healing and can be considered as a promising therapeutic approach in the treatment of diabetic nonhealing ulcers.