Recent progress of plant-derived extracellular vesicle-like nanoparticles integrated with biomaterials for skin...

The skin, serving as a crucial physical and immunological barrier, faces significant regenerative challenges after injury or dysfunction. Recently, plant-derived extracellular vesicle-like nanoparticles (PELNs) have emerged as a highly potent, cell-free therapeutic strategy for skin tissue engineering, offering rich bioactive components, low immunogenicity, and inherent biocompatibility. However, PELNs face limitations such as poor stability, weak targeting ability, and rapid clearance, hindering their clinical applications. The latest progress in integrating or engineering PELNs with functional biomaterial delivery systems provides a promising strategy to overcome these challenges. This review systematically explores the biological characteristics of PELNs, emphasizing the integration and engineering strategies with advanced biomaterials to enhance their therapeutic effects. Firstly, the synergistic mechanisms of PELN-biomaterial composites across diverse dermatological applications, including wound healing, skin photoaging, and inflammatory skin diseases were reviewed. Secondly, the corresponding mechanisms of immune microenvironment remodeling, angiogenesis, and the restoration of redox homeostasis were also summarized. Finally, the clinical translation and regulatory landscape with challenges and perspectives of PELN-biomaterial composites were analyzed.