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Research Papers

Biomechanical Comparison of Glutaraldehyde-Crosslinked Gelatin Fibrinogen Electrospun Scaffolds to Porcine Coronary Arteries

[+] Author and Article Information
E. Tamimi, D. C. Ardila, D. G. Haskett

Graduate Interdisciplinary Program
of Biomedical Engineering,
The University of Arizona,
Tucson, AZ 85721

T. Doetschman

Department of Cellular and Molecular Medicine,
The University of Arizona,
Tucson, AZ 85721;
Sarver Heart Center,
The University of Arizona,
Tucson, AZ 85724;
BIO5 Institute for Biocollaborative Research,
The University of Arizona,
Tucson, AZ 85721

M. J. Slepian

Graduate Interdisciplinary Program
of Biomedical Engineering,
The University of Arizona,
Tucson, AZ 85721;
Sarver Heart Center,
The University of Arizona,
Tucson, AZ 85724;
BIO5 Institute for Biocollaborative Research,
The University of Arizona,
Tucson, AZ 85721;
Department of Biomedical Engineering,
The University of Arizona,
Tucson, AZ 85721;
ACABI, The Arizona Center for Accelerated
BioMedical Innovation,
The University of Arizona,
Tucson, AZ 85721

R. S. Kellar

Center for Bioengineering Innovation,
Northern Arizona University,
Flagstaff, AZ 86011;
Department of Mechanical Engineering,
Northern Arizona University,
Flagstaff, AZ 86011;
Department of Biological Sciences,
Northern Arizona University,
Flagstaff, AZ 86011

J. P. Vande Geest

Associate Professor
Graduate Interdisciplinary Program
of Biomedical Engineering,
The University of Arizona,
Tucson, AZ 85721;
Department of Aerospace and Mechanical Engineering,
The University of Arizona,
Tucson, AZ 85721;
BIO5 Institute for Biocollaborative Research,
The University of Arizona,
Tucson, AZ 85721;
Department of Biomedical Engineering,
The University of Arizona,
Tucson, AZ 85721
e-mail: jpv1@email.arizona.edu

1Corresponding author.

Manuscript received March 30, 2015; final manuscript received October 15, 2015; published online November 13, 2015. Assoc. Editor: Sean S. Kohles.

J Biomech Eng 138(1), 011001 (Nov 13, 2015) (12 pages) Paper No: BIO-15-1133; doi: 10.1115/1.4031847 History: Received March 30, 2015; Revised October 15, 2015

Cardiovascular disease (CVD) is the leading cause of death for Americans. As coronary artery bypass graft surgery (CABG) remains a mainstay of therapy for CVD and native vein grafts are limited by issues of supply and lifespan, an effective readily available tissue-engineered vascular graft (TEVG) for use in CABG would provide drastic improvements in patient care. Biomechanical mismatch between vascular grafts and native vasculature has been shown to be the major cause of graft failure, and therefore, there is need for compliance-matched biocompatible TEVGs for clinical implantation. The current study investigates the biaxial mechanical characterization of acellular electrospun glutaraldehyde (GLUT) vapor-crosslinked gelatin/fibrinogen cylindrical constructs, using a custom-made microbiaxial optomechanical device (MOD). Constructs crosslinked for 2, 8, and 24 hrs are compared to mechanically characterized porcine left anterior descending coronary (LADC) artery. The mechanical response data were used for constitutive modeling using a modified Fung strain energy equation. The results showed that constructs crosslinked for 2 and 8 hrs exhibited circumferential and axial tangential moduli (ATM) similar to that of the LADC. Furthermore, the 8-hrs experimental group was the only one to compliance-match the LADC, with compliance values of 0.0006±0.00018 mm Hg−1 and 0.00071±0.00027 mm Hg−1, respectively. The results of this study show the feasibility of meeting mechanical specifications expected of native arteries through manipulating GLUT vapor crosslinking time. The comprehensive mechanical characterization of cylindrical biopolymer constructs in this study is an important first step to successfully develop a biopolymer compliance-matched TEVG.

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References

Figures

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Fig. 1

(Left) Electrospinning setup which includes a syringe pump setup with a syringe loaded with the gelatin/fibrinogen solution. The rotating translating mandrel is enclosed in an acrylic housing. (Right) Electrospun constructs after being removed from mandrel before being placed in the cross-linking chamber.

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Fig. 2

(Left) Representative construct images. (Right) Average thickness of 2, 8, and24 hrs crosslinked constructs with error bars indicating standard deviation. Double asterisks indicate p value < 0.01 (n = 3).

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Fig. 3

Gelatin/fibrinogen tubular construct loaded into the MOD

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Fig. 4

Averaged circumferential stress–strain curves for gelatin/fibrinogen constructs at 0, 10, and 30 g of axial load for constructs crosslinked for 2, 8, and 24 hrs and for the distal section of LADC. Error bars represent one standard deviation.

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Fig. 5

Averaged axial stress–strain curves at 0, 70, and 120 mm Hg for gelatin/fibrinogen constructs crosslinked for 2, 8, and 24 hrs and for the distal section of LADCs. Error bars represent one standard deviation.

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Fig. 6

CTM comparison between experimental groups and the LADC at 0, 70, and 120 mm Hg. The asterisks indicate statistical significance of the difference between each constructs experimental group and the LADC at the respective pressures, with a single asterisk indicating a p value < 0.01 and double asterisks indicating a p value < 0.001.

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Fig. 7

Axial tangential modulus comparison between experimental groups and the LADC at axial Green strain values of 0, 0.05, 0.1, and 0.15. The asterisks indicate statistical significance of the difference between each constructs experimental group and the LADC at the respective axial Green strains, with a single asterisk indicating a p value < 0.05 and double asterisks indicating a p value < 0.001.

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Fig. 8

Compliance comparison between experimental groups and the LADC. The asterisks indicate statistical significance of the difference between each constructs experimental group and the LADC at the respective axial Green strains, with double asterisks indicating a p value < 0.001.

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Fig. 9

Circumferential stress–strain fitted Fung equation surface plots for each experimental group plotted against data points from all three replicates displayed for fit evaluation and visualization. The surface plots and data points are shown only for strain ranges that overlap between all three replicates.

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Fig. 10

Axial stress–strain fitted Fung equation surface plots for each experimental group plotted against data points from all three replicates displayed for fit evaluation and visualization. The surface plots and data points are shown only for strain ranges that overlap between all three replicates.

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Fig. 11

Representative MIP images obtained from multiphoton imaging (top), and fiber orientation distribution histograms (bottom) of the constructs crosslinked for 2, 8, and 24 hrs. Ninety degree angles correspond to fibers oriented in the circumferential direction and 0 deg and 180 deg angles correspond to fibers oriented in the axial direction.

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