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Translational studies on the potential of a VEGF nanoparticle-loaded hyaluronic acid hydrogel

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posted on 09.08.2021, 11:17 by Joanne O'Dwyer, Robert MurphyRobert Murphy, Arlyng Gyveth Gonzalez VazquezArlyng Gyveth Gonzalez Vazquez, Lenka Kovarova, Martin Pravda, Vladimir Velebny, Andreas HeiseAndreas Heise, Garry DuffyGarry Duffy, Sally-Ann CryanSally-Ann Cryan
Heart failure has a five-year mortality rate approaching 50%. Inducing angiogenesis following a myocardial infarction is hypothesized to reduce cardiomyocyte death and tissue damage, thereby preventing heart failure. Herein, a novel nano-in-gel delivery system for vascular endothelial growth factor (VEGF), composed of star-shaped polyglutamic acid-VEGF nanoparticles in a tyramine-modified hyaluronic acid hydrogel (nano-VEGF-HA-TA), is investigated. The ability of the nano-VEGF-HA-TA system to induce angiogenesis is assessed in vivo using a chick chorioallantoic membrane model (CAM). The formulation is then integrated with a custom-made, clinically relevant catheter suitable for minimally invasive endocardial delivery and the effect of injection on hydrogel properties is examined. Nano-VEGF-HA-TA is biocompatible on a CAM assay and significantly improves blood vessel branching (p < 0.05) and number (p < 0.05) compared to a HA-TA hydrogel without VEGF. Nano-VEGF-HA-TA is successfully injected through a 1.2 m catheter, without blocking or breaking the catheter and releases VEGF for 42 days following injection in vitro. The released VEGF retains its bioactivity, significantly improving total tubule length on a Matrigel® assay and human umbilical vein endothelial cell migration on a Transwell® migration assay. This VEGF-nano in a HA-TA hydrogel delivery system is successfully integrated with an appropriate device for clinical use, demonstrates promising angiogenic properties in vivo and is suitable for further clinical translation.

Funding

Science Foundation Ireland (SFI) under an Investigator Award, under grant number 13/IA/1840

AMCARE consortium, a European Union’s Seventh Framework Program (FP7/2007–2013), under grant agreement number 604531

European Research Council (ERC) under the European Community’s Horizon 2020 framework program (ERC Advanced Grant ReCaP project #788753)

Children’s Health Temple Street Foundation (grant # RPAC 19-01)

History

Comments

The original article is available at https://www.mdpi.com

Published Citation

O'Dwyer J. et al. Translational studies on the potential of a VEGF nanoparticle-loaded hyaluronic acid hydrogel. Pharmaceutics. 2021;13(6):779.

Publication Date

22 May 2021

PubMed ID

34067451

Department/Unit

  • Amber (Advanced Material & Bioengineering Research) Centre
  • Anatomy and Regenerative Medicine
  • Chemistry
  • CURAM Centre for Research in Medical Devices
  • School of Pharmacy and Biomolecular Sciences
  • Tissue Engineering Research Group (TERG)

Research Area

  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine

Publisher

MDPI AG

Version

  • Published Version (Version of Record)