Chronic wounds, like diabetic foot ulcers, are skin injuries that fail to heal through the natural repair process. Current therapies often cannot restore the impaired healing process, underlining the urgent need for innovative therapeutic approaches. This research aims to develop a fully plant-based bioactive wound dressing to restore healing in chronic wounds while providing a low-cost, low-risk alternative to mammalian-derived materials. Plant-derived exosome-like nanoparticles (ENPs) were isolated from Aloe vera leaves using crossflow filtration and incorporated into a soy protein isolate (SPI) biomatrix using a modified air-assisted electrospinning technique. The isolated ENPs were first characterized by nanoparticle tracking analysis (NTA), confirming an average size of approximately 130 nm, and were then fluorescently labeled. Scanning electron microscopy and confocal imaging confirmed the formation of randomly oriented fibers with an average diameter of 350–400 nm and the uniform distribution of ENPs throughout the biomatrix. The electrospun SPI-ENP biomatrix exhibited the controlled release of ENPs over 21 days under physiological conditions. In vitro studies using human umbilical vein endothelial cells (HUVECs) demonstrated enhanced cellular internalization of ENPs and a significant increase in metabolic activity (p < 0.0001). They also exhibited effective immunomodulatory activity in macrophage cells, demonstrating their potential to modulate the immune response. Ongoing studies are evaluating the long-term bioactivity of the released ENPs in supporting key regenerative processes, including cell migration, proliferation, and angiogenesis. This work establishes a promising foundation for developing scalable, affordable, and safe bioactive wound dressings, offering a sustainable plant-based alternative to mammalian-derived materials for chronic wound healing applications.
