Three‐Dimensional Paper‐Based Model for Cardiac Ischemia

Abstract

In vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines that subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.

Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?

“…In addition, 2D monotypic cultures do not resemble the complex cellular composition of the adult heart, where CMs represent only one third of the total number of cells: they are normally incorporated within networks of smooth muscle cells/pericytes, endothelial cells and fibroblasts (Tirziu et al , 2010) and covered by epicardium on the outside and endocardium on the inside layer. The generation of cardiac microtissues (Beauchamp et al , 2015), engineered heart tissues (Zimmermann and Schneiderbanger, 2002; Turnbull et al , 2014) or 3D vascularized cardiac layers (Mosadegh et al , 2014) have been reported. These multidimensional and heterogeneous environments promote CM organization and maturity and will thus probably contribute, in the future, to enhancing the predictivity and reliability of these platforms for drug screening when compared with 2D cultures (Eder et al , 2016).…”

Multilayer three-dimensional filter paper constructs for the culture and analysis of aortic valvular interstitial cells

“…Subsequent studies from the same research group have expanded the filter paper method to include a polyethylene (terephthalate) substrate and to have the ability to analyze the effects of soluble compounds on cell behavior [22,23]. An additional study used the system to study ischemia in cardiomyocytes [24].…”

Electrically Activated Paper Actuators

“…[2] In recent years, paper has become increasingly interesting as a material in new applications. [3][4][5] For example, we and others have used it for microfluidic [6][7][8][9][10] and electroanalytical devices as the basis for low-cost diagnostics, [11,12] as 3-D scaffolds for cell growth, [13][14][15] as a substrate for printed electronics, [16][17][18][19][20][21][22] and in micro-electromechanical systems (MEMS). [16,23,24] A missing component for paper-based devices is an electrically controlled actuator that is embedded within the paper, can be fabricated by printing, and continues to operate when the paper that supports it is creased and/or folded.…”