Sequential management of burn wound healing stages through biointelligence-inspired platelet extracellular vesicle-encapsulated photodynamic diferuloylmethane.

The process of wound healing is a complex, multi-phase phenomenon crucial for optimal tissue regeneration. Traditional drug delivery systems often target specific phases of wound repair, neglecting the dynamic interplay among the stages. This limitation highlights the need for comprehensive delivery systems that cater to the holistic needs of wound healing, enhancing tissue regeneration efficiency. Herein, we explored the utility of platelet-derived extracellular vesicles (pEVs) as carriers for the phototherapeutic diferuloylmethane (DIF), resulting in a formulation termed DIF@pEVs, which is designed to sequentially address the distinct phases of wound healing. Initially, upon exposure to light, administered DIF@pEVs generate photodynamic therapy-derived reactive oxygen species during the early inflammatory phase. This generation of ROS aims to modulate the inflammatory response, induce the protective mechanisms of heat shock proteins, and kickstart the tissue regeneration process. Following this initial phase, the remaining DIF and pEVs persist in promoting tissue repair and regeneration. Ultimately, it reduces inflammation, speeds up the healing process, and promotes vascular and follicular formation in a model of burn wound skin damage, thereby supporting skin regeneration. The deployment of DIF@pEVs represents an advancement in regenerative medicine, providing a precise, versatile approach to fostering regeneration across a wide range of clinical scenarios.