Hydrogel-Integrated Heart-on-a-Chip Platform for Assessment of Myocardial Ischemia Markers

Abstract

Organ-on-a-chip platform scans offer a controllable environment and a physiological similarity to mimic human pathophysiology. In this study, a single-channel PDMS microchip was fabricated, characterized, and optimized to obtain a heart-ona-chip platform, which is integrated with a hydrogel scaffold suitable for cardiomyocyte growth inside its channel. Single-channel chips with a size of 20 × 12 mm and a channel height ranging from 60 to 100 μm were produced using photolithography and soft lithography techniques. A gelatin-embedded alginate network-based hydrogel was further augmented with 3% (v/v) collagen type I. Pore sizes were in the range of 74−153 μm for H9C2 implantation and biomimicry. The hydrogels are characterized both on PDMS surfaces and in capillaries. The primary feature distinguishing this study from previous microchip studies is that it mimics the cell microenvironment much better using different hydrogel formulations instead of creating a 2D cell culture by passing fluids, such as fibronectin, for cell adhesion. Instead of using complex microchip designs, the chip system we created intends to provide a physiologically relevant copy by using a 3D cell culture to its advantage and a simple, single-channel architecture. The microchip study was combined with cardiomyocytes to create the heart-on-a-chip system and tested under normoxic and hypoxic conditions to create a myocardial ischemia model inside this channel. As a result, this heart-on-a-chip platform was shown to be utilized for the detection of several small-size biomarkers such as adenosine, ADP, lactic acid, L-isoleucine, L-glutamic acid, and oxidized glutathione via LC-MS/MS from control conditions and a myocardial ischemia model. Cell-embedded and hydrogel matrix-supported versions of this heart-on-a-chip system were successfully prepared and shown to provide powerful outputs with myocardial ischemia markers. In light of this research, these outputs aim to develop simple and biologically effective organ-on-a-chip systems for future research.