Abstract

Decellularized Extracellular Matrix Bioinks and the External Stimuli to Enhance Cardiac Tissue Development in vitro

Sanskrita Das, Post-doctoral Research Associate, Pohang University of Science and Technology

Engineered heart tissue (EHT) holds potential as a model for in vitro tissue modeling or tissue regeneration. Different systems have been described to fabricate EHT, however, its efficacy has remained limited due to inferior functional properties of the cardiomyocytes stemming from lack of proper microenvironmental cues. The use of heart tissue-derived extracellular matrix (hdECM) bioink is considered as one of the most promising candidates due to its functional and structural similarities to native tissue. Here, a focus was made on demonstrating a correlation between the synthesis of cardiomyocyte-specific proteins and the surrounding microenvironment. Neonatal rat cardiomyocytes were encapsulated in different composition and concentration of bioinks (hdECM and collagen). The bioinks were sequentially printed using an extrusion-based 3D bioprinter and cultured either statically or dynamically. Qualitative and quantitative evaluation revealed enhanced maturation of cardiomyocytes in hdECM, unlike the collagen group under similar culture conditions. In addition, human EHT was fabricated using a low concentration of hdECM encapsulated with human induced pluripotent stem cells derived cardiomyocytes. The human EHT exhibited uniform, aligned structural arrangement of cardiac regulatory proteins and demonstrated synchronous beating motion along with propagation of calcium sparks. The study provides experimental insights regarding the establishment of a successful 3D printed EHT.