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Intravascular Ultrasound Characterization of a Tissue-Engineered Vascular Graft in an Ovine Model

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Abstract

Patients who undergo implantation of a tissue-engineered vascular graft (TEVG) for congenital cardiac anomalies are monitored with echocardiography, followed by magnetic resonance imaging or angiography when indicated. While these methods provide data regarding the lumen, minimal information regarding neotissue formation is obtained. Intravascular ultrasound (IVUS) has previously been used in a variety of conditions to evaluate the vessel wall. The purpose of this study was to evaluate the utility of IVUS for evaluation of TEVGs in our ovine model. Eight sheep underwent implantation of TEVGs either unseeded or seeded with bone marrow-derived mononuclear cells. Angiography, IVUS, and histology were directly compared. Endothelium, tunica media, and graft were identifiable on IVUS and histology at multiple time points. There was strong agreement between IVUS and angiography for evaluation of luminal diameter. IVUS offers a valuable tool to evaluate the changes within TEVGs, and clinical translation of this application is warranted.

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Abbreviations

°C:

Degrees Celsius

CI:

Confidence interval

α-SMA:

Alpha smooth muscle actin

CaVC:

Caudal vena cava

CT:

Computed tomography

IF:

Immunofluorescence

IVUS:

Intravascular ultrasound

GMP:

Good Manufacturing Practice

kg:

Kilogram

MRI:

Magnetic resonance imaging

mg:

Milligram

mm:

Millimeter

μm:

Micrometer

PBS:

Phosphate buffered saline

PCLA:

Polycaprolactone and polylactic acid

PGA:

Polyglycolic acid

TEVG:

Tissue-engineered vascular graft

vWF:

von Willebrand factor

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Acknowledgements

The Comparative Mouse Phenotyping and Pathology Shared Resource, Department of Veterinary Biosciences, and the Comprehensive Cancer Center at the Ohio State University performed tissue embedding, sectioning, and H&E staining. The Morphology Core at Nationwide Children’s Hospital performed Masson’s Trichrome staining. Assistance with biostatistical analysis was provided by Yongjie Miao of the Biostatistics Core from the Research Institute at Nationwide Children’s Hospital. We would like to acknowledge the contributions of our animal care staff, veterinary staff, and interventional cardiology team, without whom the work performed would not be possible.

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Authors and Affiliations

  1. Tissue Engineering Program, Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, WB 4154, Columbus, OH, 43205, USA

    Victoria K. Pepper, Elizabeth S. Clark, Cameron A. Best, Ekene A. Onwuka, Eric D. Heuer, Lilamarie E. Moko, Shinka Miyamoto, Hideki Miyachi, Toshiharu Shinoka & Christopher K. Breuer

  2. Department of Pediatric Surgery, Nationwide Children’s Hospital, Columbus, OH, USA

    Victoria K. Pepper & Christopher K. Breuer

  3. College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA

    Elizabeth S. Clark

  4. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Ekene A. Onwuka

  5. Division of Cardiothoracic Transplant & Mechanical Circulatory Support, Texas Heart Institute at Baylor St. Luke’s Medical Center, Houston, TX, USA

    Tadahisa Sugiura

  6. The Heart Center, Nationwide Children’s Hospital, Columbus, OH, USA

    Darren P. Berman, Sharon L. Cheatham, Joanne L. Chisolm, Toshiharu Shinoka & John P. Cheatham

  7. Department of Cardiothoracic Surgery, Nationwide Children’s Hospital, Columbus, OH, USA

    Toshiharu Shinoka

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  1. Victoria K. Pepper
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  2. Elizabeth S. Clark
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  3. Cameron A. Best
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Corresponding author

Correspondence to Christopher K. Breuer.

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Sources of Funding

Funding for this study was provided by NIH R01 HL128847 as well as internal sources from Nationwide Children’s Hospital, Columbus, OH to C.K.B. and T.S. The work presented was also supported by T32 OD010429-13 to ESC and T32AI106704 to EAO. The Comparative Mouse Phenotyping and Pathology Shared Resource is supported in part by grant P30 CA016058.

Disclosures

Support for graft production for this study was provided by Gunze Limited. Christopher Breuer, MD is also on the scientific advisory board for Cook Biomedical and is the founder of Lyst Therapeutics. The remaining authors have no conflicts of interest.

Human Subjects/Animal Subjects Statement

No human studies were carried out by the authors for this article. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

Additional information

Associate Editor Adrian Chester oversaw the review of this article

Victoria K. Pepper and Elizabeth S. Clark are shared first authors.

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Pepper, V.K., Clark, E.S., Best, C.A. et al. Intravascular Ultrasound Characterization of a Tissue-Engineered Vascular Graft in an Ovine Model. J. of Cardiovasc. Trans. Res. 10, 128–138 (2017). https://doi.org/10.1007/s12265-016-9725-x

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