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

## TL;DR

A new nanoplatform helps heart valves heal faster by delivering a molecule that boosts cell growth and reduces blood clots.

## Contribution

A biomimetic nanoplatform that combines immune evasion, targeted cell adhesion, and 2dDR-induced signaling for heart valve endothelialization.

## Key findings

- In vitro studies show enhanced endothelial cell adhesion, migration, and proliferation.
- In vivo testing in rats shows accelerated endothelial coverage and reduced thrombosis within 14 days.
- Transcriptomic and proteomic analyses reveal anti-inflammatory and regenerative effects.

## 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.

This study develops a biomimetic nanoplatform using erythrocyte membrane‐camouflaged, CD144 antibody‐functionalized nanoparticles to deliver 2‐deoxy‐D‐ribose (2dDR). This system promotes heart valve endothelialization by enhancing endothelial cell migration and proliferation via EGFR activation, while improving hemocompatibility. In vivo results show accelerated endothelial coverage and reduced thrombosis, offering a promising strategy for next‐generation tissue‐engineered heart valves.