A biodegradable, microstructured, electroconductive and nano-integrated drug eluting patch (MENDEP) for myocardial tissue engineering

We produced a microstructured, electroconductive and nano-functionalized drug-eluting

cardiac patch (MENDEP) designed to attract endogenous precursor cells, favour their

differentiation and counteract adverse ventricular remodelling in situ. MENDEP showed

mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced

impedance, controlled biodegradability, molecular recognition ability and controlled drug

release activity. In vitro, cytocompatibility and cardioinductivity were demonstrated. Migration

tests showed the chemoattractive capacity of the patches and conductivity assays showed

unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially

implanted in a rat model of ischaemia/reperfusion (I/R). Histological, immunofluorescence and

biomarker analysis indicated that implantation did not cause damage to the healthy

myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and

triggered their differentiation towards the vascular lineage. Under the patch, the myocardial

tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level

of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in

the patch group.

Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface

of the left ventricle over 4-week implantation period, underwent progressive vascularization,

did not perturb the healthy myocardium and showed great potential in repairing the infarcted

area.