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Biomanufacturing

Biomanufacturing - Poster Session B

Poster B1 - Biofabrication of an Innervated Cardiac Patch (InCaP) for Post Myocardial Infarction Repair

Thursday, October 24, 2024
2:45 PM - 3:45 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Myocardial infarction (MI) is associated with an ischemic insult resulting in necrosis of cardiac tissue as well as damage to the intrinsic autonomic nerve fibers. Tissue engineering strategies for cardiac repair demand muscle regeneration, rapid host re-vascularization, and appropriate autonomic innervations. Sympathetic input is not only critical for cardiac regeneration but also plays a crucial role in cardiac myocyte development and maturation1–3. In this study, we describe the biofabrication of a novel Innervated Cardiac Patch (InCaP) comprising pre-formed sympathetic networks and aligned cardiac myofibers to better mimic native tissue architecture. Further, InCaP is fabricated using electrospun aligned PVDF piezoelectric nanofibers that provides topographical guidance and can potentially act as an autonomous sensor-actuator system thereby enabling synchronous myocardial conductivity following MI.

Materials and

Methods:  Cardiac myocytes and sympathetic neurons were isolated from heart tissue of E16 rat pups and from the superior cervical ganglia (SCG) of P0-P1 neonatal rats, respectively. The cardiac myocytes were plated on piezoelectric (PVDF) and non-piezoelectric (PCL) nanofiber sheets, and then allowed to grow for 1-2 days before the SCGs were seeded on top of the cardiac layer. The neuro-cardiac coculture was maintained in co-culture media for 7-14 days with regular changes of media.

Results, Conclusions, and Discussions: 

Results: Cardiac myocytes and SCG were successfully cultured on piezoelectric (PVDF) and non-piezoelectric (PCL) nanofiber scaffolds (1cm2 sections). Subsequent immunohistochemistry showed uniform cardiac myocyte and sympathetic neuronal density across the scaffold surface with robust expression of cardiac troponin T and a sympathetic neuron marker, tyrosine hydroxylase (TH) (Fig 1). The presence of sympathetic neurons was further observed to increase the cardiac contraction rate per minute. Ongoing studies are aimed at understanding the role of piezoelectric scaffolds and innervation on cardiomyocyte gap-junction formation, axon ingrowth, and cardiac ion channel network using immunocytochemistry and confocal microscopy.

Conclusions: We demonstrate a novel 3D neuro-cardiac coculture system on aligned piezoelectric nanofibers that may be employed as an implantable patch to facilitate appropriate sympathetic re-innervation and reduce electrical heterogeneity between non-infarct and infarct regions following MI (Fig 1). InCaPs may aid in addressing key challenges in cardiac tissue engineering and may serve as both an in vitro test platform as well as an implantable composite tissue to facilitate functional regeneration after MI.

Acknowledgements (Optional):  

References:
1. White, I. A., Gordon, J., Balkan, W. & Hare, J. M. Sympathetic Reinnervation Is Required for Mammalian Cardiac Regeneration. Circ Res 117, 990–994 (2015).
2. Tampakakis, E. et al. Heart neurons use clock genes to control myocyte proliferation. Sci Adv 7, eabh4181 (2021).
3. Kreipke, R. E. & Birren, S. J. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal. J Physiology 593, 5057–5073 (2015).