Current Research on Aloe-Derived Extracellular Vesicles in Injury Repair

Abstract

In recent years, plant-derived extracellular vesicle–like nanoparticles have garnered significant interest as promising therapeutic agents and delivery vehicles, owing to their biocompatibility and multifaceted bioactivity. Among these, extracellular vesicles derived from Aloe species (A-EVs) have shown considerable potential in promoting tissue repair. However, a consolidated overview linking their physicochemical properties to in vivo reparative functions and clinical translatability is still lacking. This review systematically summarizes current methods for isolating and characterizing A-EVs, highlighting the technical variability that challenges standardization. Evidence is synthesized demonstrating that A-EVs facilitate injury repair through integrated mechanisms, including potent antioxidant effects via Nrf2/HO-1 pathway activation, anti-inflammatory action via macrophage polarization and NF-κB suppression, and the promotion of cellular proliferation and migration. Notably, emerging research reveals their unique capacity to induce immunogenic cell death (eg, pyroptosis) in diseased tissues, setting them apart from many other plant EV sources. Compared to EVs from other medicinal plants, A-EVs offer a distinctive combination of anthraquinone-enriched cargo, pro-healing protein profiles, and mucoadhesive properties, making them particularly suited for wound and gastrointestinal repair. Despite low immunogenicity and a natural propensity for drug encapsulation, major hurdles—such as scalable production, pharmacokinetic profiling, and rigorous safety assessment—must be overcome to advance clinical translation. By critically evaluating recent progress and existing gaps, this review clarifies the mechanistic basis for A-EVs’ reparative effects and provides a rationale for their future development as standardized, next-generation nanotherapeutics for regenerative medicine.