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Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings.

Publication ,  Journal Article
Diaz Quiroz, JF; Rodriguez, PD; Erndt-Marino, JD; Guiza, V; Balouch, B; Graf, T; Reichert, WM; Russell, B; Höök, M; Hahn, MS
Published in: ACS biomaterials science & engineering
August 2018

Achieving graft endothelialization following implantation continues to be a challenge in the development of "off-the-shelf," small-caliber, arterial prostheses. Coating grafts with biomolecules to support the retention, migration, and differentiation of adherent endothelial precursor cells (EPCs) is a promising approach toward improving graft endothelialization. esigner ollagen Scl2- with integrin binding site per strand (DC2-1X) is a Streptococcus pyogenes-derived, collagen-like protein that has previously been evaluated as a graft coating due to its ability to resist platelet aggregation and to promote attachment and migration of "late outgrowth" EPCs (EOCs). However, these prior assessments were performed in the absence of physiological shear. In addition, although DC2-1X coatings supported increased migration rates relative to native collagen coatings, EOC attachment and spreading remained inferior to collagen controls at all DC2-1X concentrations assayed. Thus, the objectives of the present work were the following: (1) to improve EOC attachment on DC2 coatings by modulating the number and spacing of DC2 integrin binding sites (IBS) and (2) to evaluate the retention, migration, and differentiation of adherent EOCs under physiological shear stress. Using single point mutations, three novel DC2 variants were generated containing either two IBS (DC2-2X) or three IBS (DC2-3X1 and DC2-3X2) per strand. After initial evaluation of the potential of each DC2 variant to support increased EOC attachment relative to DC2-1X, DC2-2X and DC2-3X1 coatings were further assessed under physiological shear for their capacity to promote EOC retention, migration, and differentiation relative to DC2-1X and collagen controls. An increase in the number of IBS from 1 to 3 significantly improved EOC retention on DC2 coatings while also supporting increased average migration rates. Moreover, EOCs on DC2-3X1 coatings showed increased gene-level expression of intermediate endothelial cell differentiation markers relative to collagen. Overall, the current results suggest that DC2-3X1 warrants further investigation as a vascular graft coating.

Duke Scholars

Published In

ACS biomaterials science & engineering

DOI

EISSN

2373-9878

ISSN

2373-9878

Publication Date

August 2018

Volume

4

Issue

8

Start / End Page

2934 / 2942

Related Subject Headings

  • 4003 Biomedical engineering
  • 0903 Biomedical Engineering
 

Citation

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MLA
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Diaz Quiroz, J. F., Rodriguez, P. D., Erndt-Marino, J. D., Guiza, V., Balouch, B., Graf, T., … Hahn, M. S. (2018). Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings. ACS Biomaterials Science & Engineering, 4(8), 2934–2942. https://doi.org/10.1021/acsbiomaterials.8b00070
Diaz Quiroz, Juan Felipe, Patricia Diaz Rodriguez, Josh D. Erndt-Marino, Viviana Guiza, Bailey Balouch, Tyler Graf, William M. Reichert, Brooke Russell, Magnus Höök, and Mariah S. Hahn. “Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings.ACS Biomaterials Science & Engineering 4, no. 8 (August 2018): 2934–42. https://doi.org/10.1021/acsbiomaterials.8b00070.
Diaz Quiroz JF, Rodriguez PD, Erndt-Marino JD, Guiza V, Balouch B, Graf T, et al. Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings. ACS biomaterials science & engineering. 2018 Aug;4(8):2934–42.
Diaz Quiroz, Juan Felipe, et al. “Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings.ACS Biomaterials Science & Engineering, vol. 4, no. 8, Aug. 2018, pp. 2934–42. Epmc, doi:10.1021/acsbiomaterials.8b00070.
Diaz Quiroz JF, Rodriguez PD, Erndt-Marino JD, Guiza V, Balouch B, Graf T, Reichert WM, Russell B, Höök M, Hahn MS. Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings. ACS biomaterials science & engineering. 2018 Aug;4(8):2934–2942.
Journal cover image

Published In

ACS biomaterials science & engineering

DOI

EISSN

2373-9878

ISSN

2373-9878

Publication Date

August 2018

Volume

4

Issue

8

Start / End Page

2934 / 2942

Related Subject Headings

  • 4003 Biomedical engineering
  • 0903 Biomedical Engineering