Customizable Microfluidic Origami Liver-on-a-Chip (oLOC).

The design and manufacture of an origami-based liver-on-a-chip device are presented, together with demonstrations of the chip's effectiveness at recapitulating some of the liver's key in vivo architecture, physical microenvironment, and functions. Laser-cut layers of polyimide tape are folded together with polycarbonate nanoporous membranes to create a stack of three adjacent flow chambers separated by the membranes. Endothelial cells are seeded in the upper and lower flow chambers to simulate sinusoids, and hepatocytes are seeded in the middle flow chamber. Nutrients and metabolites flow through the simulated sinusoids and diffuse between the vascular pathways and the hepatocyte layers, mimicking physiological microcirculation. Studies of cell viability, metabolic functions, and hepatotoxicity of pharmaceutical compounds show that the endothelialized liver-on-a-chip model is conducive to maintaining hepatocyte functions and evaluation of the hepatotoxicity of drugs. Our unique origami approach speeds chip development and optimization, effectively simplifying the laboratory-scale fabrication of on-chip models of human tissues without necessarily reducing their structural and functional sophistication.

Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels.

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

Complexation-induced resolution enhancement of 3D-printed hydrogel constructs.

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Our study reports a unique method of resolution enhancement purely relying on post-printing treatment of hydrogel constructs. By immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge, shrinking can rapidly occur resulting in various degrees of reduced dimensions comparing to the original pattern. This phenomenon, caused by complex coacervation and water expulsion, enables us to reduce linear dimensions of printed constructs while maintaining cytocompatible conditions in a cell type-dependent manner. We anticipate our shrinking printing technology to find widespread applications in promoting the current 3D printing capacities for generating higher-resolution hydrogel-based structures without necessarily having to involve complex hardware upgrades or other printing parameter alterations.