Abstract
Effective and quick screening and cardiotoxicity assessment are very crucial for drug development. Here, a novel composite hydrogel composed of carbon fibers (CFs) with high conductivity and modulus with polyvinyl alcohol (PVA) is reported. The conductivity of the composite hydrogel PVA/CFs is similar to that of natural heart tissue, and the elastic modulus is close to that of natural heart tissue during systole, due to the incorporation of CFs. PVA/CFs remarkably enhance the maturation of neonatal rat cardiomyocytes (NRCM) in vitro by upregulating the expression of α-actinin, troponin T, and connexin-43, activating the signaling pathway of α5 and β1 integrin-dependent ILK/p-AKT, and increasing the level of RhoA and hypoxia-inducible factor-1α. As a result, the engineered cell sheet-like constructs NRCM@PVA/CFs display much more synchronous, stable, and robust beating behavior than NRCM@PVA. When exposed to doxorubicin or isoprenaline, NRCM@PVA/CFs can retain effective beating for much longer time or change the contractile rate much faster than NRCM@PVA, respectively, therefore representing a promising heart-like platform for in vitro drug screening and cardiotoxicity assessment.
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