Bioactive Anti-Thrombotic Modification of Decellularized Matrix for Vascular Applications

Jeremy J. Glynn, Monica Hinds

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The decellularized matrix derived from porcine small intestinal submucosa (SIS) is a widely used biomaterial being investigated for numerous applications. Currently, thrombus deposition and neointimal hyperplasia have limited the use of SIS in some vascular applications. To limit these detrimental processes, this work applies bioactive, endothelial-inspired properties to the material. SIS is modified with the endothelial cell membrane protein thrombomodulin and the glycosaminoglycan heparin to facilitate protein C activation and anticoagulant activity, respectively. Modifying SIS with thrombomodulin alone enables robust activated protein C (APC) generation, and thrombomodulin activity is maintained after prolonged exposure to fluid shear and blood plasma. Heparin-modified SIS has a potent anticoagulant activity. When both modifications are applied sequentially, SIS modified first with thrombomodulin then with heparin retains the full activity of each individual modification. Tubular SIS devices are connected to a baboon arteriovenous shunt to quantify thrombus deposition on these materials. After being exposed to flowing whole blood for 60 min, SIS devices modified first with thrombomodulin then with heparin have significantly less platelet accumulation compared to unmodified SIS devices. These studies demonstrate that modifying SIS with thrombomodulin and heparin confers APC generation and anticoagulant activity that results in reduced thrombogenesis.

Original languageEnglish (US)
Pages (from-to)1439-1446
Number of pages8
JournalAdvanced healthcare materials
Volume5
Issue number12
DOIs
StatePublished - Jun 22 2016

Keywords

  • coagulation
  • decellularized biomaterial
  • heparin
  • platelets
  • thrombomodulin

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

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