Endothelial retention and phenotype on carbonized cardiovascular implant surfaces

Christopher M. Frendl, Scott M. Tucker, Nadeem A. Khan, Mandy B. Esch, Shrinidhi Kanduru, Thong M. Cao, Andrés J. García, Michael R. King, Jonathan T. Butcher

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Heart valve disease is an increasing clinical burden for which there is no effective treatment outside of prosthetic replacement. Over the last 20 years, clinicians have increasingly preferred the use of biological prosthetics to mechanical valves despite their superior durability because of the lifelong anticoagulation therapy that is required. Mechanical valve surface engineering has largely focused on being as non-thrombogenic as possible, but despite decades of iteration has had insufficient impact on the anticoagulation burden. In this study, we systematically evaluate the potential for endothelialization of the pyrolytic carbon surface used in mechanical valves. We compared adsorbed adhesion ligand type (collagen I, fibronectin, laminin, and purified adhesion domain fragments GFOGER and FN7-10) and concentration on endothelial adhesion rates and adhesion strength on Medtronic-Hall prosthetic valve surfaces. Regardless of ligand type or concentration, endothelial adhesion strengthening was insufficient for their intended ultra-high shear stress environment. We then hypothesized that microfabricated trenches would reduce shear stress to tolerable levels while maintaining endothelial access to the flow stream, thereby promoting a confluent and anticoagulant endothelial monolayer. Computational fluid dynamics simulations predicted an empirical relationship of channel width, depth, and spacing that would maintain interior surface shear stress within tolerable levels. Endothelial cells seeded to confluence in these channels retained a confluent monolayer when exposed to 600dyn/cm2 shear stress for 48h regardless of applied adhesive ligand. Furthermore, sheared EC expressed a mature anti-coagulant profile, including endothelial nitric oxide synthase (eNOS), VE-cadherin, and significantly downregulated plasminogen activator inhibitor-1 (PAI-1). As a final test, channeled pyrolytic carbon surfaces with confluent EC reduced human platelet adhesion 1000-fold over pyrolytic carbon alone. These results advance a promising biohybrid approach to enable active moderation of local coagulative response in mechanical heart valves, which could significantly extend the utility of this important treatment for heart valve disease.

Original languageEnglish (US)
Pages (from-to)7714-7723
Number of pages10
JournalBiomaterials
Volume35
Issue number27
DOIs
StatePublished - Sep 2014

Keywords

  • Adhesion peptide
  • Computational fluid dynamics
  • Hemodynamics
  • Hemostasis
  • Mechanical heart valves
  • Platelet adhesion

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Endothelial retention and phenotype on carbonized cardiovascular implant surfaces'. Together they form a unique fingerprint.

  • Cite this

    Frendl, C. M., Tucker, S. M., Khan, N. A., Esch, M. B., Kanduru, S., Cao, T. M., García, A. J., King, M. R., & Butcher, J. T. (2014). Endothelial retention and phenotype on carbonized cardiovascular implant surfaces. Biomaterials, 35(27), 7714-7723. https://doi.org/10.1016/j.biomaterials.2014.05.075