Erythrocytes and erythrocyte membrane vesicles have shown promise for personalized drug delivery through passive immune evasion, yet their active role in immune phagocytosis remains largely unexplored. Here, we introduce a paradigm based on phosphatidylserine-everted erythrocyte membrane vesicles that trigger efferocytosis, enabling immune-mediated tissue regeneration rather than immune evasion. Incorporation of these phosphatidylserine-everted erythrocyte membrane vesicles into small-diameter vascular grafts markedly enhances endothelialization, suppresses calcification, and improves long-term patency in a rabbit carotid artery replacement model. Preclinical evaluation in a large canine model further demonstrates superior performance compared with clinically used expanded polytetrafluoroethylene grafts. This study establishes engineered phosphatidylserine-everted erythrocyte membrane vesicles as a versatile, customizable, and cost-effective biointerface for vascular grafts and other blood-contacting devices, providing a compelling strategy to harness innate immune mechanisms for regenerative medicine. Erythrocyte membrane vesicles (EMVs) are promising for drug delivery but their role in immune-mediated regeneration is unclear. Here the authors show that phosphatidylserine-everted EMVs trigger efferocytosis to enhance endothelialization, reduce calcification, and improve vascular graft patency in animal models.
Wang et al. (Thu,) studied this question.