A Semi-Three-Dimensional Bioprinted Neurocardiac System for Tissue Engineering of a Cardiac Autonomic Nervous System Model

Ivana Hernandez; Salma P Ramirez; Wendy V Salazar; Sarahi Mendivil; Andrea Guevara; Akshay Patel; Carla D Loyola; Zayra N Dorado; Binata Joddar

doi:10.3390/bioengineering10070834

A Semi-Three-Dimensional Bioprinted Neurocardiac System for Tissue Engineering of a Cardiac Autonomic Nervous System Model

Bioengineering (Basel). 2023 Jul 14;10(7):834. doi: 10.3390/bioengineering10070834.

Authors

Ivana Hernandez^{1

2}, Salma P Ramirez^{1

2}, Wendy V Salazar¹, Sarahi Mendivil¹, Andrea Guevara¹, Akshay Patel^{1

3}, Carla D Loyola^{1

2}, Zayra N Dorado^{1

2}, Binata Joddar^{1

2

4}

Affiliations

¹ Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), The University of Texas at El Paso, El Paso, TX 79968, USA.
² Department of Metallurgical, Materials and Biomedical Engineering, M201 Engineering, The University of Texas at El Paso, 500 W. University Avenue, El Paso, TX 79968, USA.
³ Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA.
⁴ Border Biomedical Research Center, The University of Texas at El Paso, 500 W. University Avenue, El Paso, TX 79968, USA.

Abstract

In this study, we designed a tissue-engineered neurocardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for the regeneration of cardiac tissue. A three-dimensional (3D) bioprinted neurocardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid-differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted, where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo. The voids in this 3D structure were methodically filled in using a NC-gel mixture and crosslinked. Confocal fluorescent imaging using microtubule-associated protein 2 (MAP-2) and anticholine acetyltransferase (CHAT) antibodies for labeling the NCs and the MyoD1 antibody for the CMs revealed functional coupling between the two cell types in the final crosslinked structure. These data confirmed the development of a relevant neurocardiac model that could be used to study neurocardiac modulation under physiological and pathological conditions.

Keywords: 3D bioprinting; 3D tissue model; cardiomyocytes; neuroblastoma cells; neurocardiac junctions.

Grants and funding

1854008/National Science Foundation