By Russ Banham
The creation of regenerative human tissue, bones and even organs like livers and kidneys via three-dimensional (3D) bioprinting is a fast-growing branch of science marked by ongoing achievements. The goal is to precisely make body parts from a patient’s genetic matter to match the tissues or organs being replaced, thereby limiting the risk of rejection.
While 3D bioprinting research and development largely has been confined to the laboratory, medical researchers at the forefront of this technology say progress is quickly being made. Two recent achievements include the growing of human cells using 3D bioprinting techniques without the use of scaffold-like devices, and the creation of liver tissue in three-dimensions for drug testing purposes in clinical trials.
The latter is paving the way for pharmaceutical companies to improve the efficacy of drugs that test for toxicity in the clinical trial process. At present, scientists testing a drug designed to improve liver function are limited to studies in rats or using two-dimensional liver tissue.
“Pharmaceutical companies often miss aspects of liver toxicity because they are relying on these two current methods of testing, which are highly imperfect,” said Keith Murphy, chairman and CEO of Organovo Holdings, Ind., a public company engaged in 3d bioprinting research and development. “This results in a drug being greenlighted to the next phase of clinical trials because researchers, despite it later being found to be toxic.”
In other words, a significant number of drugs move forward in the clinical trial process because the current testing methods failed to detect toxicity. “There is a ten percent failure rate,” Murphy said. “This eats up enormous time and money with no benefit to those who are sick.”
Now Available to Pharmaceutical Companies
Organovo is helping to alter this ill-fated course. The company takes healthy liver cells from a donor and then bioprints liver tissue in three dimensions for drug testing purposes. “This is complex tissue we make,” Murphy said. “Previous methods only use about 90 percent of the cells in a liver and put them in a flat petri dish. We are able to add the remaining minority cell populations to our tissue. We then orient them in a three dimensional architecture, with all the cells interacting with each other to replicate the right biology.”
The three-dimensional liver tissue proved its merit in a recent study sponsored by a major pharmaceutical company that has asked to remain anonymous. “We were able to show that the tissue could detect the toxicity of a drug that had previously been deemed safe in standards preclinical animal studies,” Murphy said. “The toxic profile of this compound was only discovered after its use in a large number of patients—at significant expense. Basically, we were able to predict the drug problems that the previous methods had failed to detect.”
The 3D bioprinted liver tissue is now commercially available to pharmaceutical companies for immediate use in their clinical trials. A company provides a drug compound to Organovo, which exposes it to the liver tissue at its facility in San Diego, and subsequently provides the results.
More Promising Research
Equally promising is research being conducted at the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina. Dr. Anthony J. Atala, the institute’s director, cited progress being made in eradicating the wide use of scaffolds shaped like the organ or tissue being engineered to manufacture three-dimensional organs and tissue. The scaffolds support the cells as they multiply, before harmlessly dissolving. Researchers had searched for another means of growing cells without the hands-on approach required using scaffolding. This means is now at hand.
“We’ve been able to show the feasibility of bioprinting the cells using a bio-ink that acts as a glue of sorts,” Dr. Atala said. “We’re now at the point where we will soon be injecting the printed cells into patients in the first phase of clinical trials.”
Since the cells are drawn from the patient’s own DNA, Dr. Atala is confident of success. “But, we still have to prove the safety of this, since we don’t know if or how the cells may change as they grow outside the body before being brought back into it,” he noted.
If the clinical trials prove successful, Dr. Atala said the next step would be to apply this research to the manufacture of an actual kidney.
Each of these developments, assuming they eventually become part of routine clinical care, poses risk to a broad array of parties, including medical researchers, manufacturers of bioprinted tissues and organs, the pharmaceutical companies that create drugs proven to be safe through tests using bioprinted tissues, and even health care providers like hospitals and physician practices prescribing their use. As this important research commences, it is imperative that the global insurance industry become a partner in helping these entities identify and manage the associated financial exposures and provide cost-effective methods of risk transfer.