Abstract 420: Micromolded Cardiac Network Patches for Treatment of Infarcted Heart
Currently, engineering a functional cardiac patch for infarct repair is hampered by the lack of methods to:
supply oxygen and nutrients inside the patch, and
control the 3D alignment of cardiac cells over a relatively large area (>1cm2).
Here we describe a novel method to reproducibly fabricate cardiac network patches with pores of controlled size and elongation in order to improve oxygen diffusion and locally control 3D cell alignment inside the patch. Specifically, PDMS molds were cast against a microfabricated master made of UV-curable resin and injected with a mixture of neonatal rat cardiac cells, fibrin gel, and matrigel (Fig. A1– 4⇓). After a week of culture, initial cell density was increased an order of magnitude by gel compaction. After 4 weeks, differentiated cardiomyocytes were densely packed, highly aligned and interconnected throughout the patch (Fig. B⇓). The majority of non-cardiomyocytes were localized at the outer surface of the networks. Transmembrane voltage was optically mapped using a voltage sensitive dye (di-4-ANEPPS) and a 504 channel photodiode array. Tissue networks vigorously and synchronously contracted at rates that decreased over time in culture from 4~5Hz to~1Hz. At week 4, electrical propagation was uniformly anisotropic with longitudinal and transverse conduction velocities of 20.5 ± 0.6cm/s and 14.0 ± 1.4cm/s, respectively (Fig. C1–2⇓). Maximum steady-state capture rates (point stimulus) were 3.8 ± 1.3Hz. No arrhythmias resulted from rapid pacing. The mean action potential duration was 257 ± 37ms. Future studies include assessment of electrical and mechanical properties of the cardiac network patch as a function of pore size and geometry.