Microfabrication of AngioChip, a biodegradable polymer scaffold with microfluidic vasculature

Abstract

Microengineered biomimetic systems for organ-on-a-chip or tissue engineering purposes often fail as a result of an inability to recapitulate the in vivo environment, specifically the presence of a well-defined vascular system. To address this limitation, we developed an alternative method to cultivate three-dimensional (3D) tissues by incorporating a microfabricated scaffold, termed AngioChip, with a built-in perfusable vascular network. Here, we provide a detailed protocol for fabricating the AngioChip scaffold, populating it with endothelial cells and parenchymal tissues, and applying it in organ-on-a-chip drug testing in vitro and surgical vascular anastomosis in vivo. The fabrication of the AngioChip scaffold is achieved by a 3D stamping technique, in which an intricate microchannel network can be embedded within a 3D scaffold. To develop a vascularized tissue, endothelial cells are cultured in the lumen of the AngioChip network, and parenchymal cells are encapsulated in hydrogels that are amenable to remodeling around the vascular network to form functional tissues. Together, these steps yield a functional, vascularized network in vitro over a 14-d period. Finally, we demonstrate the functionality of AngioChip-vascularized hepatic and cardiac tissues, and describe direct surgical anastomosis of the AngioChip vascular network on the hind limb of a Lewis rat model.

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

“…Hydrogel‐based microvascular networks are desirable for engineering functional 3D vascularized tissues in OOC . Zhang et al developed an AngioChip scaffold with a built‐in perfusable vascular network fabricated using a synthetic polymer POMaC by 3D stamping technique, in which a complex microchannel network can be embedded within a 3D scaffold . POMaC, which is characterized by the properties of elasticity and photopolymerization, can be rapidly assembled under mild conditions and biodegraded by hydrolysis.…”

Revolutionizing Drug Testing Platforms by Leveraging Angiochip and Flight Data Recorder Technologies

“…This unique combination of culturing and fabrication techniques allows for the chip to simulate cardiac muscle contractions. Epinephrine, a heart rate accelerating drug, was administered to the chip to determine its efficacy as a drug testing platform (2). As expected, epinephrine induced quicker electrical impulses and contractions along the entire Angiochip, mimicking physiological responses.…”

“…However, the distinct physiology of animal primates renders this practice unsuitable for large-scale, translatable drug testing studies and has driven the use of human tissues as its own platform. At the University of Toronto, Dr. Milica Radisic's research group has designed a nano-scale "organ on a chip" called the Angiochip (2). Combining this novel technology with the Flight Data Recorder, which was recently developed by Dr. Samantha A. Morris at the University of Washington, will allow for independent testing of novel drugs while tracking the lineage and identity of individual cells in human tissues cultured on the Angiochip (3).…”

“…The Angiochip is a nano-scale chip that cultures endothelial and parenchymal cells to simulate human heart function ( Figure 1) (4). Its unique host-vascularized network is created upon implantation using bioprinting techniques, hydrogels and various sacrificial materials (2). A well-established vascular system is essential for providing oxygen and nutrients while sustaining surrounding cells.…”

A Multimaterial Microphysiological Platform Enabled by Rapid Casting of Elastic Microwires

“…Following full perfusion, the POMaC prepolymer was exposed to UV light to generate an array of crosslinked elastomeric wires, after which the PDMS mold was removed. To mitigate the effects of batch‐to‐batch variation of the bulk polymer solution to the mechanical stiffness of the UV‐crosslinked polymer wires, the UV crosslinking energy was adjusted for each batch of polymers so that the Young's modulus (measured with a myograph as we described) of the bulk polymer after crosslinking is 33 ± 3 kPa. UV‐crosslinked POMaC wires consistently attached to the polystyrene base, resulting in multiple microwires cast across the entire plate, suspended across 96 microwells (Figure C).…”