Nano-textured polydimethylsiloxane cantilever with embedded silver nanowire networks for drug screening applications

Abstract

Drug-induced cardiotoxicity is the primary cause of heart failure and leading to withdrawal of drugs from the market. Although in vitro animal models are successfully used in fundamental research on heart physiology, cardiac disease, and cardiovascular drug development, the immature cardiomyocytes utilized in existing in vitro screening techniques cannot effectively replicate the natural physiology of adult cardiomyocytes. As a result, the results obtained in vivo contradict those obtained in vitro. Herein, we propose a nanotextured polydimethylsiloxane cantilever integrated with embedded silver nanowire (AgNWs-E-PDMS) to enhance cardiomyocyte maturation. The cardiomyocytes cultured on the functional PDMS cantilever exhibit an enhanced cell viability, synchronized and stable beating behavior, and Ca2+ transient signals and cell adhesion. The Western blot (WB) and reverse transcription polymerase chain reaction (RT-qPCR) tests also showed that connexin-43 (Cx43) protein and its gene expression in cardiomyocytes are 4.59 and 1.75 times higher than in the control group of cardiomyocytes. The performance of the cantilever-based screening platform is also verified by performing sequential drug analysis using neonatal rat ventricular myocytes (NRVM) and human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) on nanotextured PDMS and AgNWs-E-PDMS cantilevers. We expect that the proposed cantilever device will help reduce the risk of drug-induced heart disease in the early stages of drug development.