Cardiac cell networks on elastic microgrooved scaffolds

Abstract
We tested the potential of elastic topographically-modified (EM) scaffolds to serve as an atrophy countermeasure for engineered cardiac cell constructs. We compared the structural and electromechanical characteristics of cardiac syncytia on flat rigid and elastic microgrooved scaffolds, cultured and tested under identical conditions. Our paired test analysis demonstrated a significant increase (with respect to control) in sustained synchronous contractile activity, diastolic Ca/sup 2+/ (>115%), systolic Ca/sup 2+/ levels (>200%), maximum upstroke velocity (>440%) and maximum recovery velocity (>600%) in the EM-grown cell constructs (n=9 pairs, p<0.005 for all parameters). 3D reconstructions of confocal immunocy-to-chemistry images of cell cytoskeleton and gap junctional proteins (Connexin 43) confirmed a more mature in vivo-like intra- and inter-cellular organization for the EM case. Our results suggest that self-organized cell activity in response to the supporting matrix might effectively mimic anti-atrophy effects reported for external electrical or mechanical stimulation. We conclude, that topographically-modified elastic scaffolds might serve as strong positive inotropic effectors, can promote self-organized synchronous mechanical and electrical activity, and therefore produce structurally and functionally superior cardiac tissue equivalents with improved viability.