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.

• Publication year

  2025

• Venue

  Advancement of science

• Publication date

  2025-11-12

• Fields of study

  Medicine, Engineering

• Identifiers
  DOI 10.1002/advs.202514170PMID 41221559PMCID 12866836
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Impact of Aortic Valve Replacement Choices in Young Patients: Investing for a Lifetime of Success.

  2025cited by this paper
• PLGA/HA sustained-release system loaded with liraglutide for the treatment of diabetic periodontitis through inhibition of necroptosis

  2025cited by this paper
• Nanocarriers and macrophage interaction: from a potential hurdle to an alternative therapeutic strategy

  2025cited by this paper
• Engineered hybrid cell membrane nanosystems for treating cardiovascular diseases

  2025cited by this paper
• Targeted 2‐Deoxy‐D‐Ribose Delivery by Biomimetic Nanoplatform Activates EGFR for Accelerated Heart Valve Endothelialization

  2025cited by this paper
• Constructing Immunomodulator Biosynthesis Factory in Grafting‐From DNA Hydrogel for Heart Valve Regeneration

  2025cited by this paper
• Stealth missiles with precision guidance: A novel multifunctional nano-drug delivery system based on biomimetic cell membrane coating technology

  2025cited by this paper
• Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives

  2025cited by this paper
• Dehydrocurvularin-loaded mPEG-PLGA nanoparticles for targeted breast cancer drug delivery: preparation, characterization, in vitro, and in vivo evaluation

  2024cited by this paper
• Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids.

  2024cited by this paper
• Matrix Metalloproteinase‐Responsive Controlled Release of Self‐Assembly Nanoparticles Accelerates Heart Valve Regeneration In Situ by Orchestrating Immunomodulation

  2024cited by this paper
• Cross-Linking Agents in Three-Component Materials Dedicated to Biomedical Applications: A Review

  2024cited by this paper
• Ubiquitination of VE-cadherin regulates inflammation-induced vascular permeability in vivo

  2024cited by this paper
• CeO2 In Situ Growth on Red Blood Cell Membranes: CQD Coating and Multipathway Alzheimer's Disease Therapy under NIR.

  2024cited by this paper
• Changes in the Biomechanical Properties of Corneal Stromal Lens after Collagen Crosslinking Induced by EDC-NHS

  2024cited by this paper
• Site-selective antibody-lipid conjugates for surface functionalization of red blood cells and targeted drug delivery.

  2024cited by this paper
• Neutrophil-derived nanovesicles deliver IL-37 to mitigate renal ischemia-reperfusion injury via endothelial cell targeting.

  2024cited by this paper
• Vascular reconstruction of the decellularized biomatrix for whole-organ engineering—a critical perspective and future strategies

  2023cited by this paper
• Red blood cell-derived materials for cancer therapy: Construction, distribution, and applications

  2023cited by this paper
• Recent progress in functional modification and crosslinking of bioprosthetic heart valves

  2023cited by this paper
• Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

  2023cited by this paper
• Lineage Tracing Identifies Dynamic Contribution of Endothelial Cells to Cardiac Valve Mesenchyme During Development

  2023cited by this paper
• Biofunctionalized Decellularized Tissue-Engineered Heart Valve with Mesoporous Silica Nanoparticles for Controlled Release of VEGF and RunX2-siRNA against Calcification

  2023cited by this paper
• Calcification in Pulmonary Heart Valve Tissue Engineering

  2023cited by this paper
• Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine

  2023cited by this paper
• Multifunctional nanoparticle-VEGF modification for tissue-engineered vascular graft to promote sustained anti-thrombosis and rapid endothelialization

  2023cited by this paper
• The loading of C-type natriuretic peptides improved hemocompatibility and vascular regeneration of electrospun poly(ε-caprolactone) grafts.

  2022cited by this paper
• In Vivo Evaluation of PCL Vascular Grafts Implanted in Rat Abdominal Aorta

  2022cited by this paper
• Probing the solvation of the α-helix with extended amide III bands in Raman optical activity.

  2022cited by this paper
• Surface functionalization of anticoagulation and anti-nonspecific adsorption with recombinant hirudin modification.

  2022cited by this paper
• Targeting drugs to tumours using cell membrane-coated nanoparticles

  2022cited by this paper
• Targeted delivery of nanomedicines for promoting vascular regeneration in ischemic diseases

  2022cited by this paper
• Transplantation of Endothelial Progenitor Cells: Summary and prospect.

  2022cited by this paper
• Decellularized extracellular matrix: New promising and challenging biomaterials for regenerative medicine.

  2022cited by this paper
• To PEGylate or not to PEGylate: immunological properties of nanomedicine's most popular component, poly(ethylene) glycol and its alternatives.

  2021cited by this paper
• Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor

  2021cited by this paper
• Surgical pericardial heart valves: 50 Years of evolution.

  2021cited by this paper
• Antibody-engineered red blood cell interface for high-performance capture and release of circulating tumor cells.

  2021cited by this paper
• Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation

  2021cited by this paper
• Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity

  2020cited by this paper
• Management of Asymptomatic Severe Aortic Stenosis: Evolving Concepts in Timing of Valve Replacement.

  2020cited by this paper
• Assessment of the Angiogenic Potential of 2-Deoxy-D-Ribose Using a Novel in vitro 3D Dynamic Model in Comparison With Established in vitro Assays

  2020cited by this paper
• Monocyte chemoattractant protein‑1 promotes the proliferation, migration and differentiation potential of fibroblast‑like synoviocytes via the PI3K/P38 cellular signaling pathway.

  2020cited by this paper
• Toward an Artificial Endothelium: Development of Blood-Compatible Surfaces for Extracorporeal Life Support.

  2020cited by this paper
• Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers.

  2020cited by this paper
• 2-Deoxy-d-ribose (2dDR) upregulates vascular endothelial growth factor (VEGF) and stimulates angiogenesis.

  2020cited by this paper
• Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome.

  2020cited by this paper
• Heart valves cross-linked with erythrocyte membrane drug-loaded nanoparticles as a biomimetic strategy for anti-coagulation, anti-inflammation, anti-calcification, and endothelialization.

  2020cited by this paper
• Development of highly functional bioengineered human liver with perfusable vasculature.

  2020cited by this paper
• Recent advances in the formulation of PLGA microparticles for controlled drug delivery

  2020cited by this paper
• Antibody-Conjugated Electrospun Vascular Scaffolds to Enhance In Situ Endothelialization.

  2020cited by this paper
• Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis

  2020cited by this paper
• Regulation of Lipoprotein Homeostasis by Self-Assembling Peptides.

  2020cited by this paper
• Materials and manufacturing perspectives in engineering heart valves: a review

  2019cited by this paper
• Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application

  2019cited by this paper
• Endothelialization of cardiovascular devices.

  2019cited by this paper
• The Hemocompatibility of Nanoparticles: A Review of Cell–Nanoparticle Interactions and Hemostasis

  2019cited by this paper
• Tissue Engineering at the Blood‐Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development

  2018cited by this paper
• Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure, mechanical property and biocompatibility study

  2018cited by this paper
• Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis

  2018cited by this paper
• Polyurethane/polyurethane nanoparticle-modified expanded poly(tetrafluoroethylene) vascular patches promote endothelialization.

  2018cited by this paper
• Transcatheter Aortic Heart Valves: Histological Analysis Providing Insight to Leaflet Thickening and Structural Valve Degeneration.

  2018cited by this paper
• Radical polymerization-crosslinking method for improving extracellular matrix stability in bioprosthetic heart valves with reduced potential for calcification and inflammatory response.

  2018cited by this paper
• Pericardial tissue for cardiovascular application: an in-vitro evaluation of established and advanced production processes

  2018cited by this paper
• Stromal Cell-Derived Factor-1α Promotes Endothelial Colony-Forming Cell Migration Through the Ca2+-Dependent Activation of the Extracellular Signal-Regulated Kinase 1/2 and Phosphoinositide 3-Kinase/AKT Pathways

  2018cited by this paper
• Fucoidan/VEGF-based surface modification of decellularized pulmonary heart valve improves the antithrombotic and re-endothelialization potential of bioprostheses.

  2018cited by this paper
• Mechanical or Biologic Prostheses for Aortic‐Valve and Mitral‐Valve Replacement

  2017cited by this paper
• A Rat Model for the In Vivo Assessment of Biological and Tissue-Engineered Valvular and Vascular Grafts

  2017cited by this paper
• Recellularization of decellularized heart valves: Progress toward the tissue-engineered heart valve

  2017cited by this paper
• Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years.

  2016cited by this paper
• Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading

  2016cited by this paper
• Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges.

  2016cited by this paper
• The anti-angiogenic action of 2-deoxyglucose involves attenuation of VEGFR2 signaling and MMP-2 expression in HUVECs.

  2015cited by this paper
• Cell membrane-camouflaged nanoparticles for drug delivery.

  2015cited by this paper
• VE-cadherin in vascular development: a coordinator of cell signaling and tissue morphogenesis.

  2015cited by this paper
• Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions

  2015cited by this paper
• PLGA-based nanoparticles as cancer drug delivery systems.

  2013cited by this paper
• Rho GTPases in platelet function

  2013cited by this paper
• Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells.

  2010cited by this paper
• 2-Deoxy-D-ribose, a downstream mediator of thymidine phosphorylase, regulates tumor angiogenesis and progression.

  2009cited by this paper
• VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation.

  2007cited by this paper
• Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets

  2006cited by this paper
• Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease.

  2005cited by this paper
• Blockage of 2-Deoxy-d-Ribose-Induced Angiogenesis with Rapamycin Counteracts a Thymidine Phosphorylase-Based Escape Mechanism Available for Colon Cancer under 5-Fluorouracil Therapy

  2004cited by this paper
• Thymidine phosphorylase induces angiogenesis in vivo and in vitro: an evaluation of possible mechanisms

  2003cited by this paper
• The birth of the platelet

  2003cited by this paper
• Suppression of thymidine phosphorylase-mediated angiogenesis and tumor growth by 2-deoxy-L-ribose.

  2002cited by this paper
• Role of CD47 as a marker of self on red blood cells.

  2000cited by this paper
• A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices.

  1999cited by this paper
• Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules.

  1999cited by this paper

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

  2025cites this paper