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

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.