The Revolution Will Not be Televised, But it Will be 3D Printed

Courtesy Photo | Collaboration between Defense Threat Reduction Agency, Chemical and Biological Technologies Department and Wake Forest Institute for Regenerative Medicine resulted in developing organ-on-a-chip technology. The organ-on-a-chip is a multichannel 3-D microfluidic cell culture chip which simulates the activities, mechanisms and physiological response of entire organs. (DTRA Photo by Jacob Mosholder)  

FORT BELVOIR, VA, UNITED STATES

06.04.2019

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

The long and winding journey that leads to the Food and Drug Administration (FDA) approval of a medicine is extremely expensive and littered with failed candidates. In “Drugs, Devices, and the FDA: Part 1” (published in April 2016 by JACC: Basic to Translational Science), Gail A. Van Norman, MD, writes that new drugs can take an average of 12 years before they go on the market — from animal studies to clinical trials in humans to FDA approval — and the cost may exceed a billion dollars. That’s if the drug candidate proceeds from one research step to another and the FDA deems it effective and safe for human use. But many potential candidates do not pass this rigorous testing process because what works in studies with animals may not work in humans, or worse, may cause harm.

Still, the FDA mandates that drug trials first occur in animals, resulting in the current timeline before a new drug is available to warfighters and the public. However, that timeline may shrink thanks to an innovative combination of 3D printing and collaboration between the Defense Threat Reduction Agency’s Chemical and Biological Technologies Department (DTRA CB) and Wake Forest Institute for Regenerative Medicine (WFIRM).

For years, pharmaceutical developers have been searching for ways to assess a drug candidate’s safety in humans before expensive clinical trials begin. WFIRM, led by director Anthony Atala, M.D., may hold the key. DTRA CB partnered with Atala and WFIRM to develop an Integrated Organoid Testing System (INGOTS). This system uses human organ cells, coupled with 3D bioprinted structures and microfluidic devices (e.g., tiny objects, such as a chip of glass, with grooved channels to transport fluids), to create interconnected organlike entities (organoids). With INGOTS, there is potential for creating liver, heart and lung cells that live, regenerate and function as one unit, as full-sized organs do.

In 2016, Atala won an R&D Magazine Innovator of the Year award for his efforts in developing 3D bioprinting. In this process, supportive biocompatible hydrogels are used along with human donor cells to create complex 3D living organs that function. Hydrogels are polymers — a material with a repeating molecular structure — bloated with water. Hydrogels do not dissolve in water, and their composition is flexible like human tissue. Think of hydrogels as “scaffolds,” as described by Tibbitt and Anseth in “Extracellular Matrix Mimics for 3D Cell Culture” (published in July 2009 by Biotechnology and Bioengineering). Scientists can place human cells living outside the body in hydrogels, and these cells can grow into structures such as a heart. This 3D living organ has potential for use in humans and in a variety of research, including drug trials.

Three-dimensional printing of organs and other biomatter involves additional complexities, such as the choice of compatible biological matrices, cell types, growth and differentiation factors, and other technical challenges to create the structural and functional aspects of the desired native organ cells. One goal of this technology is to create multiple types of tissue or organ prototypes for use in humans. Another is to produce miniaturized human organoid systems that interconnect and could predict the tolerability of a drug candidate before significant expenses are incurred through clinical trials — revolutionizing the drug development process and timeline.

The promise of 3D bioprinted human organoid systems lies in their interconnected nature. This is critical as drug candidates can do well in a test tube or a petri dish but then fail to produce the same results in a body where interconnected systems exist. For example, a drug may only show its toxicity to the heart following metabolism in the liver. Using these interconnected organoids, researchers have successfully replicated the failures of many drug candidates that had to be withdrawn. INGOTS can demonstrate potential toxicities before human trials and could be used to refine the development of lead drug candidates — dramatically reducing time, money and the number of nonhuman animals undergoing laboratory tests.

Currently, before the FDA allows human testing of a new drug, it requires a number of trials in accepted animal models. Animal models are nonhuman animals (such as mice or rabbits) that either naturally or artificially (i.e., created by researchers) have cells that share the potential to acquire a disease found in humans. Such animal models are particularly important to the development of medical countermeasures against chemical and biological warfare agents, which prevent human efficacy trials.

With INGOTS, DTRA CB and WFIRM can also create organoid systems of animal models for testing new drug candidates. Then, depending on the effectiveness and success of the drug in that phase, it could be used in human organoid systems. To that end, DTRA is starting a new effort at WFIRM to create interconnected animal organoids created from animal models commonly used by researchers in drug development and for regulatory approval. DTRA and WFIRM’s success supports increased confidence in INGOTS for the FDA.

This latest iteration of INGOTS will eventually provide improved safety by allowing for drug trials in human organoid systems outside the human body. These advances can speed development of new therapeutics to better protect warfighters and the public from disease and the ever-evolving threats of both naturally occurring and engineered chemical and biological weapons.

• Date Taken: 06.04.2019
• Date Posted: 06.04.2019 15:19
• Story ID: 325352
• Location: FORT BELVOIR, VA, US