Successful endothelialization and remodeling of a cell-free small-diameter arterial graft in a large animal model

Maxwell T Koobatian; Sindhu Row; Randall J Smith Jr; Carmon Koenigsknecht; Stelios T Andreadis; Daniel D Swartz

doi:10.1016/j.biomaterials.2015.10.020

Successful endothelialization and remodeling of a cell-free small-diameter arterial graft in a large animal model

Biomaterials. 2016 Jan:76:344-58. doi: 10.1016/j.biomaterials.2015.10.020. Epub 2015 Oct 14.

Authors

Maxwell T Koobatian¹, Sindhu Row², Randall J Smith Jr³, Carmon Koenigsknecht⁴, Stelios T Andreadis⁵, Daniel D Swartz⁶

Affiliations

¹ Department of Physiology and Biophysics, University at Buffalo, The State University of New York, Amherst, NY, USA.
² Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY, USA.
³ Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, NY, USA.
⁴ Department of Pediatrics, University at Buffalo, The State University of New York, Amherst, USA.
⁵ Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY, USA; Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, NY, USA; Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA. Electronic address: sandread@buffalo.edu.
⁶ Department of Physiology and Biophysics, University at Buffalo, The State University of New York, Amherst, NY, USA; Department of Pediatrics, University at Buffalo, The State University of New York, Amherst, USA; Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA. Electronic address: swartzda@buffalo.edu.

Abstract

The large number of coronary artery bypass procedures necessitates development of off-the-shelf vascular grafts that do not require cell or tissue harvest from patients. However, immediate thrombus formation after implantation due to the absence of a healthy endothelium is very likely. Here we present the successful development of an acellular tissue engineered vessel (A-TEV) based on small intestinal submucosa that was functionalized sequentially with heparin and VEGF. A-TEVs were implanted into the carotid artery of an ovine model demonstrating high patency rates and significant host cell infiltration as early as one week post-implantation. At one month, a confluent and functional endothelium was present and the vascular wall showed significant infiltration of host smooth muscle cells exhibiting vascular contractility in response to vaso-agonists. After three months, the endothelium aligned in the direction of flow and the medial layer comprised of circumferentially aligned smooth muscle cells. A-TEVs demonstrated high elastin and collagen content as well as impressive mechanical properties and vascular contractility comparable to native arteries. This is the first demonstration of successful endothelialization, remodeling, and development of vascular function of a cell-free vascular graft that was implanted in the arterial circulation of a pre-clinical animal model.

Keywords: Cell-free vascular graft; Ovine carotid model; Small intestinal submucosa; Vascular endothelial growth factor; Vascular tissue engineering.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Blood Vessel Prosthesis*
Cell-Free System
Endothelium, Vascular / cytology*
Female
Heparin
Human Umbilical Vein Endothelial Cells
Humans
Models, Animal*
Sheep
Vascular Endothelial Growth Factor A

Substances

Vascular Endothelial Growth Factor A
Heparin

Grants and funding

R01 HL086582/HL/NHLBI NIH HHS/United States