Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small‐Diameter Arteries

Author:

Carrabba Michele1ORCID,Fagnano Marco1,Ghorbel Mohamed T1,Rapetto Filippo12,Su Bo3,De Maria Carmelo45,Vozzi Giovanni45,Biglino Giovanni16,Perriman Adam W.7,Caputo Massimo12,Madeddu Paolo1

Affiliation:

1. Bristol Heart Institute School of Translational Health Sciences Bristol Medical School University of Bristol Bristol BS2 8HW UK

2. Cardiac Surgery University Hospitals Bristol NHS Foundation Trust Bristol BS2 8HW UK

3. Bristol Dental School University of Bristol Bristol BS2 8HW UK

4. Research Center “E. Piaggio” University of Pisa Largo L. Lazzarino 1 56122 Pisa Italy

5. Department of Information Engineering University of Pisa Via G. Caruso 16 56122 Pisa Italy

6. Cardiorespiratory Unit Great Ormond Street Hospital for Children NHS Foundation Trust London WC1N 3JH UK

7. School of Cellular and Molecular Medicine University of Bristol Bristol BS8 1TD UK

Abstract

AbstractThe availability of grafts to replace small‐diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue‐engineered vascular graft that aims to match the natural structure of small‐size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co‐electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell‐laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi‐automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post‐implantation. These promising data open a new avenue to developing an artery‐like product for reconstructing small‐diameter blood vessels.

Funder

Medical Research Council

British Heart Foundation

NIHR Bristol Biomedical Research Centre

National Institute for Health Research Health Protection Research Unit

Publisher

Wiley

Subject

Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials

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