Plant-derived extracellular vesicles in skin and bone tissue engineering: current status, challenges, and future perspectives

Plant-derived extracellular vesicles (PDEVs) are bioactive nanoscale vesicles secreted by plant cells, which have recently gained attention as promising therapeutic agents in tissue engineering owing to their low immunogenicity, inherent biological activities, and potential as drug delivery vehicles. This review comprehensively outlines the general properties, application-specific characteristics, and isolation techniques of PDEVs, with a particular emphasis on their roles in facilitating cell proliferation, differentiation, and immunomodulation to promote tissue regeneration. We further discuss the therapeutic efficacy of PDEVs derived from various plant sources across different tissue engineering contexts, as well as the application of engineered PDEVs in tailored regenerative strategies. In comparison to mammalian extracellular vesicles, PDEVs present distinct advantages, including minimized ethical concerns and reduced risks of immune rejection. Nevertheless, challenges remain for their clinical translation, such as the lack of standardized isolation protocols and inadequate assessment of long-term in vivo safety. This article synthesizes current understanding of PDEVs, underscores their multifunctional potential, and offers perspectives on engineering approaches aimed at enhancing their therapeutic performance. With continued development, PDEVs may emerge as innovative tools in tissue engineering, facilitating tissue repair and regeneration either through their innate bioactivity or as engineered drug delivery systems.