Hydrogel-Integrated\nHeart-on-a-Chip Platform for Assessment\nof Myocardial Ischemia Markers

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