A feasibility study of a multimodal stimulation bioreactor for the conditioning of stem cell seeded cardiac patches via electrical impulses and pulsatile perfusion

Article type: Research Article

Authors: Herrmann, Florian Ernst Martin^a; | Lehner, Anja^{a; b} | Koenig, Fabian^a | Hollweck, Trixi^a | Fano, Cornelia^c | Dauner, Martin^c | Eissner, Guenther^d | Hagl, Christian^a | Akra, Bassil^a

Affiliations: [a] Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilian University, Munich, Germany | [b] Department of Pediatric Cardiology and Pediatric Intensive Care, Grosshadern Medical Centre, Ludwig Maximilian University, Munich, Germany | [c] German Institutes of Textile and Fiber Research (DITF), Denkendorf, Germany | [d] Systems Biology Ireland, University College Dublin, Dublin, Ireland

Correspondence: [*] Corresponding author: Dr. med. Florian Herrmann, Department of Cardiac Surgery, Laboratory for Tissue Engineering, Grosshadern Medical Centre, Ludwig Maximilian University, Marchioninistraße 15, 81377 Munich, Germany. Tel.: 089 4400 72436; Fax: 089 4400 78873; E-mail: Florian.Herrmann@med.uni-muenchen.de

Abstract: BACKGROUND/OBJECTIVE:Ischemic heart disease is a major cause of mortality worldwide. Myocardial tissue engineering aims to create transplantable units of myocardium for the treatment of myocardial necrosis caused by ischemic heart disease – bioreactors are used to condition these bioartificial tissues before application. METHODS:Our group developed a multimodal bioreactor consisting of a linear drive motor for pulsatile flow generation (500 ml/min) and an external pacemaker for electrical stimulation (10 mA, 3 V at 60 Hz) using LinMot-Talk Software to synchronize these modes of stimulation. Polyurethane scaffolds were seeded with 0.750 × 106 mesenchymal stem cells from umbilical cord tissue per cm2 and stimulated in our system for 72 h, then evaluated. RESULTS:After conditioning histology showed that the patches consisted of a cell multilayer surviving stimulation without major damage by the multimodal stimulation, scanning electron microscopy showed a confluent cell layer with no cell-cell interspaces visible. No cell viability issues could be identified via Syto9-Propidium Iodide staining. CONCLUSIONS:This bioreactor allows mechanical stimulation via pulsatile flow and electrical stimulation through a pacemaker. Our stem cell-polyurethane constructs displayed survival after conditioning. This system shows feasibility in preliminary tests.

Keywords: Bioreactors, tissue engineering, heart disease, myocardium, stem cells

DOI: 10.3233/BME-181031

Journal: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 37-48, 2019