Printing biohybrid materials for bioelectronic cardio-3D-cellular constructs

Paola Sanjuan-Alberte; Charlie Whitehead; Joshua N Jones; João C Silva; Nathan Carter; Simon Kellaway; Richard J M Hague; Joaquim M S Cabral; Frederico C Ferreira; Lisa J White; Frankie J Rawson

doi:10.1016/j.isci.2022.104552

Printing biohybrid materials for bioelectronic cardio-3D-cellular constructs

iScience. 2022 Jun 7;25(7):104552. doi: 10.1016/j.isci.2022.104552. eCollection 2022 Jul 15.

Authors

Paola Sanjuan-Alberte^{1

2

3}, Charlie Whitehead¹, Joshua N Jones¹, João C Silva^{2

3

4}, Nathan Carter⁵, Simon Kellaway^{1

6}, Richard J M Hague⁷, Joaquim M S Cabral^{2

3}, Frederico C Ferreira^{2

3}, Lisa J White¹, Frankie J Rawson¹

Affiliations

¹ Regenerative Medicine and Cellular Therapies, School of Pharmacy, Biodiscovery Institute, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
² Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
³ Associate Laboratory i4HB-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
⁴ Centre for Rapid and Sustainable Product Development, Polytechnic of Leiria, 2430-038 Marinha Grande, Portugal.
⁵ Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ UCL Centre for Nerve Engineering, University College London, London WC1E 6BT, UK.
⁷ Centre for Additive Manufacturing, Faculty of Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

Abstract

Conductive hydrogels are emerging as promising materials for bioelectronic applications as they minimize the mismatch between biological and electronic systems. We propose a strategy to bioprint biohybrid conductive bioinks based on decellularized extracellular matrix (dECM) and multiwalled carbon nanotubes. These inks contained conductive features and morphology of the dECM fibers. Electrical stimulation (ES) was applied to bioprinted structures containing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). It was observed that in the absence of external ES, the conductive properties of the materials can improve the contractile behavior of the hPSC-CMs, and this effect is enhanced under the application of external ES. Genetic markers indicated a trend toward a more mature state of the cells with upregulated calcium handling proteins and downregulation of calcium channels involved in the generation of pacemaking currents. These results demonstrate the potential of our strategy to manufacture conductive hydrogels in complex geometries for actuating purposes.

Keywords: Bioelectronics; Cardiovascular medicine; Materials science.