Biomimetic modification of poly(vinyl alcohol)

Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy

Deirdre E.J. Anderson, Katie P. Truong, Matthew W. Hagen, Evelyn K.F. Yim, Monica Hinds

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Poly(vinyl alcohol) (PVA) has shown promise as a biomaterial for cardiovascular application. However, its antifouling properties prevent in vivo endothelialization. This work examined the endothelialization and thrombogenicity of modified PVA with different concentrations of proteins and adhesion peptides: collagen, laminin, fibronectin, GFPGER, YIGSR, and cRGD. Material surface properties were quantified, and the endothelialization potential was determined with human endothelial colony forming cells. Additionally, platelet attachment was assessed in vitro with human platelet rich plasma, and promising samples were tested in an ex vivo shunt model. This well-established arteriovenous shunt model was used with and without clinically-relevant antiplatelet therapies, specifically acetylsalicylic acid (ASA) with and without clopidogrel to examine the minimum necessary treatment to prevent thrombosis. Collagen, laminin, and GFPGER biomolecules increased endothelialization, with GFPGER showing the greatest effect at the lowest concentrations. GFPGER-PVA tubes tested under whole blood did exhibit an increase in platelet (but not fibrin) attachment compared to plain PVA and clinical controls. However, application of ASA monotherapy reduced the thrombogenicity of GFPGER-PVA below the clinical control with the ASA. This work is significant in developing cardiovascular biomaterials—increasing endothelialization potential while reducing bleeding side effects by using an antiplatelet monotherapy, typical of clinical patients. Statement of significance: We modified the endothelialization potential of synthetic, hydrogel vascular grafts with proteins and peptides of the vascular tissue matrix. Cell attachment was dramatically increased with the GFPGER peptide, and while some additional platelet attachment was seen under flow with whole blood, this was completely knocked down using clinical antiplatelet monotherapy. This indicates that long-term patency of this biomaterial could be improved without the associated bleeding risk of multiple platelet therapies.

Original languageEnglish (US)
JournalActa Biomaterialia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Biomimetics
Platelets
Thrombosis
Alcohols
Blood Platelets
Aspirin
clopidogrel
Peptides
Biocompatible Materials
Laminin
tyrosyl-isoleucyl-glycyl-seryl-arginine
Blood Vessels
Collagen
Biomaterials
Acids
Hemorrhage
Blood
Platelet-Rich Plasma
Surface Properties
Hydrogel

Keywords

  • Endothelial cell
  • Extracellular matrix
  • Hydrogel
  • Thrombosis
  • Vascular graft

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Biomimetic modification of poly(vinyl alcohol) : Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy. / Anderson, Deirdre E.J.; Truong, Katie P.; Hagen, Matthew W.; Yim, Evelyn K.F.; Hinds, Monica.

In: Acta Biomaterialia, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Poly(vinyl alcohol) (PVA) has shown promise as a biomaterial for cardiovascular application. However, its antifouling properties prevent in vivo endothelialization. This work examined the endothelialization and thrombogenicity of modified PVA with different concentrations of proteins and adhesion peptides: collagen, laminin, fibronectin, GFPGER, YIGSR, and cRGD. Material surface properties were quantified, and the endothelialization potential was determined with human endothelial colony forming cells. Additionally, platelet attachment was assessed in vitro with human platelet rich plasma, and promising samples were tested in an ex vivo shunt model. This well-established arteriovenous shunt model was used with and without clinically-relevant antiplatelet therapies, specifically acetylsalicylic acid (ASA) with and without clopidogrel to examine the minimum necessary treatment to prevent thrombosis. Collagen, laminin, and GFPGER biomolecules increased endothelialization, with GFPGER showing the greatest effect at the lowest concentrations. GFPGER-PVA tubes tested under whole blood did exhibit an increase in platelet (but not fibrin) attachment compared to plain PVA and clinical controls. However, application of ASA monotherapy reduced the thrombogenicity of GFPGER-PVA below the clinical control with the ASA. This work is significant in developing cardiovascular biomaterials—increasing endothelialization potential while reducing bleeding side effects by using an antiplatelet monotherapy, typical of clinical patients. Statement of significance: We modified the endothelialization potential of synthetic, hydrogel vascular grafts with proteins and peptides of the vascular tissue matrix. Cell attachment was dramatically increased with the GFPGER peptide, and while some additional platelet attachment was seen under flow with whole blood, this was completely knocked down using clinical antiplatelet monotherapy. This indicates that long-term patency of this biomaterial could be improved without the associated bleeding risk of multiple platelet therapies.",
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