Targeted 2‐Deoxy‐ D ‐Ribose Delivery by Biomimetic Nanoplatform Activates EGFR for Accelerated Heart Valve Endothelialization

Abstract Tissue‐engineered heart valves face clinical translation challenges due to delayed endothelialization. To overcome this, a biomimetic erythrocyte membrane‐camouflaged nanoplatform is engineered to synergistically orchestrate endothelial cell (EC) homing through three mechanisms. The red blood cell membrane coating evades immune clearance and enhances hemocompatibility, while surface‐conjugated CD144 antibodies enable high‐affinity targeting of vascular endothelial cadherin receptors for selective EC adhesion. The poly(lactic‐co‐glycolic acid) core provides sustained release of 2‐deoxy‐D‐ribose, which activates EGFR–MAPK signaling to drive cytoskeletal reorganization and potentiate EC migration/proliferation. In vitro studies demonstrate significantly enhanced EC adhesion strength, directional migration, and proliferative activity. Transcriptomic analysis reveals attenuated TNF‐α/NFκB pathways and upregulated extracellular matrix‐assembly genes. In a rat abdominal aorta model, the platform accelerates formation of a confluent endothelial monolayer within 14 days, with physiological collagen remodeling and minimal thrombus formation. Proteomic profiling confirms downregulated PI3K–Akt‐driven inflammation and neutrophil extracellular trap formation. This multifunctional nanoplatform uniquely bridges antibody‐mediated EC recruitment with 2‐deoxy‐D‐ribose‐induced regenerative signaling, establishing a transformative paradigm for next‐generation tissue‐engineered heart valves with enhanced durability.