Tissue engineered in-vitro vascular patch fabrication using hybrid 3D printing and electrospinning

Isabel Mayoral; Elisa Bevilacqua; Gorka Gómez; Abdelkrim Hmadcha; Ignacio González-Loscertales; Esther Reina; Julio Sotelo; Antonia Domínguez; Pedro Pérez-Alcántara; Younes Smani; Patricia González-Puertas; Ana Mendez; Sergio Uribe; Tarik Smani; Antonio Ordoñez; Israel Valverde

doi:10.1016/j.mtbio.2022.100252

Tissue engineered in-vitro vascular patch fabrication using hybrid 3D printing and electrospinning

Mater Today Bio. 2022 Apr 14:14:100252. doi: 10.1016/j.mtbio.2022.100252. eCollection 2022 Mar.

Authors

Isabel Mayoral¹, Elisa Bevilacqua¹, Gorka Gómez¹, Abdelkrim Hmadcha^{2

3}, Ignacio González-Loscertales⁴, Esther Reina⁵, Julio Sotelo^{6

7}, Antonia Domínguez⁸, Pedro Pérez-Alcántara⁵, Younes Smani⁹, Patricia González-Puertas⁵, Ana Mendez¹⁰, Sergio Uribe^{7

11}, Tarik Smani^{1

12}, Antonio Ordoñez¹, Israel Valverde^{1

10

13

14}

Affiliations

¹ Cardiovascular Pathophysiology Group, Institute of Biomedicine of Seville- IBiS, University of Seville /HUVR/CSIC, Seville, Spain.
² Advanced Therapies and Regenerative Medicine Research Group.General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain.
³ Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain.
⁴ Department Mechanical, Thermal and Fluids Engineering, School of Engineering, University of Málaga, Málaga, Spain.
⁵ Department of Mechanical and Manufacturing Engineering, University of Seville, Seville, Spain.
⁶ School of Biomedical Engineering, Universidad de Valparaíso, Valparaíso, Chile.
⁷ Millennium Institute for Intelligent Healthcare Engineering, iHEALTH, Millennium Nucleus in Cardiovascular Magnetic Resonance, Cardio MR, and Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁸ Doxa Microfluidics, SL, Malaga, Spain.
⁹ Department of Molecular Biology and Biochemical Engineering, Andalusian Center of Developmental Biology, CSIC, University of Pablo de Olavide, Seville, Spain.
¹⁰ Pediatric Cardiology Unit, Hospital Virgen Del Rocio, Seville, Spain.
¹¹ Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
¹² Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, Spain.
¹³ School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
¹⁴ Department of Pharmacology, Pediatric and Radiology, School of Medicine, University of Seville, Seville, Spain.

Abstract

Three-dimensional (3D) engineered cardiovascular tissues have shown great promise to replace damaged structures. Specifically, tissue engineering vascular grafts (TEVG) have the potential to replace biological and synthetic grafts. We aimed to design an in-vitro patient-specific patch based on a hybrid 3D print combined with vascular smooth muscle cells (VSMC) differentiation. Based on the medical images of a 2 months-old girl with aortic arch hypoplasia and using computational modelling, we evaluated the most hemodynamically efficient aortic patch surgical repair. Using the designed 3D patch geometry, the scaffold was printed using a hybrid fused deposition modelling (FDM) and electrospinning techniques. The scaffold was seeded with multipotent mesenchymal stem cells (MSC) for later maturation to derived VSMC (dVSMC). The graft showed adequate resistance to physiological aortic pressure (burst pressure 101 ± 15 mmHg) and a porosity gradient ranging from 80 to 10 μm allowing cells to infiltrate through the entire thickness of the patch. The bio-scaffolds showed good cell viability at days 4 and 12 and adequate functional vasoactive response to endothelin-1. In summary, we have shown that our method of generating patient-specific patch shows adequate hemodynamic profile, mechanical properties, dVSMC infiltration, viability and functionality. This innovative 3D biotechnology has the potential for broad application in regenerative medicine and potentially in heart disease prevention.

Keywords: 3D printing; Electrospinning; Endothelin Receptor A, ETA; Endothelin Receptor B, ETB; Mesenchymal stem cells; Reverse Transcription, Rt; Three-dimensional, 3D; Tissue engineering; Vascular graft; anti-alpha-smooth muscle actin, α-SMA; anti-cluster of differentiation 31, CD31; anti-fibroblast specific protein 1, FSP1; anti-smooth muscle protein 22, SM-22; bone morphogenetic protein, BMP4; computation fluid dynamic, CFD; computed tomography, CT; derived VSMC, dVSMC; endothelin-1, ET-1; extracellular matrix, ECM; fused deposition modelling, FDM; mesenchymal stem cells, MSC; platelet-derived growth factor composed by two beta chains, PDGF-BB; room temperature, RT; tissue engineering vascular grafts, TEVG; transforming growth factor beta 1, TGFβ-1; vascular smooth muscle cells, VSMC; wall shear stress, WSS; western blotting, WB.