High Modulus Conductive Hydrogels Enhance In Vitro Maturation and Contractile Function of Primary Cardiomyocytes for Uses in Drug Screening

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.

Plasticized poly(vinylalcohol) and poly(vinylpyrrolidone) based patches with tunable mechanical properties for cardiac tissue engineering applications

“…There were no significant differences in the metabolic activity of cells among all the groups ( p < 0.05). This suggests that PVA–PVP patches with or without glycerol and propylene glycol platicizers, cytocompatible for supporting the growth and metabolism of CMs (Chiu et al, 2014; Wu et al, 2018). These observations are also in concurrence with previous studies showing cellular proliferation of neonatal CMs on PVA (Wu et al, 2018) and those of H9C2 cardiac cells in this study.…”

Engineering Biomaterials to Guide Heart Cells for Matured Cardiac Tissue

“…In addition, culture of neonatal rat heart cells for 14 days yielded an increased metabolic activity, which suggests that the incorporation of carbon fibers not only increases cardiac-specific gene expression, but also intensifies contraction and electrical coupling. In another study, high conductivity and modulus composite hydrogel was developed using a synthetic material, i.e., polyvinyl alcohol (PVA) with carbon fibers (CFs) [126]. The conductivity and elastic modulus of PVA/CFs were similar to those of natural heart tissue, and it was confirmed that the expression of maturation markers, such as α-actinin, troponin T, and connexin-43, was increased in the culture of neonatal rat cardiomyocytes.…”

“…Polyvinyl alcohol with carbon fibers 3D scaffold -Improved conductivity and elastic modulus [126] In this review, biomaterials are divided into two types: those of natural and synthetic materials. Each has its pros and cons in terms of the fabrication of cardiac tissues and organoids.…”

Nano‐ and Microfabrication for Engineering Native‐Like Muscle Tissues

“…And electromechanical coupling between CMs were observed. Conductive additives, including reduced graphene oxide, gold nanorod, and carbon fibers are added into hydrogels to improve their conductivity and promote the function of engineered tissues. Engineered skeletal muscle tissues may present specific responses upon external electrical stimulations .…”