In Vivo Assessment of a Tissue‐Engineered Vascular Graft in a Rat Model

• Published in: The FASEB journal Vol. 30; no. S1
• Main Authors: MacIsaac, Corina, Stringa, Pablo, Lausada, Natalia, Nieponice, Alejandro, Geest, Jonathan Vande
• Format: Journal Article
• Language: English
• Published: 01-04-2016
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.30.1_supplement.600.27

Abstract only
Heart disease is the leading cause of death in the United States, of which coronary artery disease (CAD) is one of the primary types. The current treatment of CAD involves bypassing the blocked coronary artery with an auxiliary blood vessel obtained from elsewhere in the patient's body. As an alternative to using this type of bypass graft, much research has been done on the fabrication of a biocompatible tissue engineered vascular graft (TEVG). The development of this TEVG is hypothesized to eliminate problems of bypass graft failure and compliance mismatch present in the current treatment. The basis of the TEVG is a scaffold which must provide (1) mechanical support of the TEVG and (2) a mesh for cells to proliferate and migrate through. This is sought to be achieved by electrospinning non‐synthetic biopolymers (gelatin, fibrinogen, collagen and tropoelastin) into a tubular construct. This procedure generates a thin fibrous mesh which allows for cell growth within the construct. The use of non‐synthetic biopolymers allows the scaffold to better compliance match a native coronary artery, as well as favor cell attachment. Preliminary experiments have been performed with different combinations and layering of the biopolymers, various speeds at which the construct was electrospun, and different amounts of glutaraldehyde cross‐linking time. Success has resulted from electrospinning constructs from a 10% by volume solution 80:20 gelatin/fibrinogen (w/w) in 1,1,1,3,3,3‐Hexafluoro‐2‐propanol (HFP). By analyzing the mechanical properties of these constructs with a microbiaxial optomechanical testing apparatus, the constructs have shown stress and strain relationships comparable to previously tested porcine left descending coronary arteries. Fluorescence imaging has also shown that porcine aortic smooth muscle cells will migrate and proliferate within this TEVG.
In addition to mechanical and
in vitro
cell culture testing,
in vivo
assessment of the acellular TEVGs has also been performed. This was achieved by performing infrarenal aortic interpositional graft placement surgery to implant the construct within a rat's aorta. This is a survival surgery and the rats remained alive for up to a month before sacrificing for analysis. Preliminary results of the
in vivo
assessments necessitated the use of synthetic polymer incorporated into the construct for added strength to be sutured at the anastomoses. However, results of these preliminary assessments show the effectiveness of using this surgery for analysis of graft function
in vivo
. Future research involves increasing the strength of the construct without the addition of a synthetic polymer, as well as seeding endothelial cells onto the constructs before implantation.
Support or Funding Information
Funding for this research is provided by: NIH 1R2HL111990 to JPVG (Co‐I Doetschman and Slepian) and HHMI 52006942 to the Biomedical Research Abroad: Vistas Open! program.