Explaining the science behind regenerative manufacturing

Futuristic biotech engineering developments would drive Kamen’s vision for ARMI
Dean Kamen|!!| founder of DEKA Research and Development Inc.

The futuristic, yet attainable, vision of manufacturing blood, skin and organs will require a vast biotech and engineering industry, says Dean Kamen, the driver behind the newly formed Advanced Regenerative Manufacturing Institute.

In December, Kamen’s Manchester-based DEKA Research and Development Inc. was awarded $85 million over five years to create an industry that would sell bioengineered products to the U.S. Department of Defense to treat severely injured soldiers. 

The goal — creating a fully functional organ — will take longer than five years, says Kamen, but with the support of 26 academic and medical research institutions and 46 companies across the country, ARMI has formed a list of priorities. 

Top priorities include working with universities to form a pipeline of skilled talent; creating hardware to expand the cell line that will be used in research and development; providing 3-D modeling using real human cells in an engineered, monitored environment; and focusing on manufacturing simpler structures such as blood and skin.

If successful, it will not only result in bioengineered material, but also faster Food and Drug Administration approval and lower costs — changing the landscape of the health care industry. 

“Among our major partners are giant pharmaceutical companies. We all know why that little pill costs so much money. It took them many years to figure out how the stuff in that pill might affect that tumor,” says Kamen. 

Typically, it takes six to eight years for researchers to conduct human trials, after successfully growing cells in a Petri dish and testing in a 2-D environment, says Kamen.

“It’s not very exact and the modeling is not a very good mapping,” argues Kamen, of the current testing methods leading up to human trials. “What typically happens is they took the first five or six or seven years, they probably spent half a billion dollars, and then they finally get the right to do a Phase 1 trial and almost all the time it fails. Why did it fail? Well, because it wasn’t on a 2-D system anymore, it was a 3-D organ in which there was angiogenesis, there was blood flowing into it. It’s very different to be in a real person than scratched onto the back of a guinea pig or a rat.”

ARMI, Kamen proposes, could change the manner in which early research and development is done.

“What if we could build tumoroids? What if we could give you a 3-D model using real human cells in a real engineered environment where we could really monitor everything? That could, for the drug companies, be a way to dramatically shorten the time it takes to develop a drug and to test a drug, and not to be surprised that so many of them fail,” says Kamen. “What would that mean to the public? The development time gets shorter, the risk of side effects in real life is much lower, which would all make it more cost-effective.”

Lowering costs

Chronic conditions like diabetes constitute most of the health care costs in the United States, says Kamen. 

Kamen led DEKA’s development of HomeChoice peritoneal dialysis system for Baxter International Inc. HomeChoice allows patients to be dialyzed in the privacy of their home. 

“Dialysis costs [over] $100 billion a year. It’s 18 percent of the entire [Medicare] budget,” says Kamen. “And for many people with organ failure, a transplant is not a realistic option. This is an important issue for ARMI board member Martine Rothblatt [CEO of United Therapeutics], who notes that there are 200,000 deaths annually from end-stage lung disease and only 2,000 lung transplants annually.”

But the regenerative medicine opportunity could change that, says Kamen. 

“What if we could give people a new pancreas, instead of insulin everyday and pumps?” says Kamen.

It’s Kamen’s vision of using manufacturing expertise -— drawing in companies with little or no experience in biotechnology but vast knowledge of production lines — that made his grant proposal to the Department of Defense stand out, he says.

And it was a unique opportunity. As Kamen will point out, over the past two decades, most of the federal funding for stem cell research is from the National Science Foundation and National Institutes of Health.

But the Department of Defense was tasked to put together a plan to attract not just researchers, but organizations that would take the existing science and turn it into an industry, with finished products that could be purchased by the federal government’s biggest purchaser. 

In putting together the proposal, Kamen approached Milwaukee-based Rockwell Automation, which automates everything from automobile production to building semiconductor equipment.  

“I said, ‘You’re going to commit to support this venture because if it works, and we have basically a showplace here in Manchester that proves that we can bring these things to scale, we’re going to create a whole new set of industry customers for you. You like supplying the automotive giants, well wouldn’t you like to supply an industry that’s making organs for people?’ And they would. And so the chairman himself said, ‘Count us in. We want to be a part of it.’”

Creating a new industry

Kamen then approached Autodesk, which is based out of San Rafael, Calif., but has long had a presence in the Manchester Millyard.

“We need the software to do the very sophisticated modeling. Well the biggest single company out there that does sophisticated computer modeling of structures is Autodesk,” says Kamen. After an in-person meeting, board member and former CEO Carl Bass agreed.

From there, Kamen has flown around the country, expanding the list of industry and academic partners. 

Focusing on manufacturing basic, single-cell structures like skin tissue, blood cells, even bone scaffolds, will be among the first endeavors ARMI embarks on, says Kamen. 

The demand for those would be “huge,” he said,” citing help for treating burn victims and bone reconstruction.

With too few donors, there’s also demand for blood. 

“What if we could build a system where you can take some of your cells and some pluripotent or generic, universal donor cells, and what if we could build an engineered system to manufacture cells like blood? That’s a huge opportunity, but again it uses some of the same engineering sources we have to develop. It’s going to use some of the same students, we hope they [the University of New Hampshire] will create. And it will help create industry to create synthetic blood.”

After development of simple, single-cell structures that might be used in patients, ARMI will next focus on multiple-cell bioengineered products, such as pieces of organs, before building whole organs.

“What I’m trying to show you is we’re going to climb a ladder here,” says Kamen.

There are two ways human organs could be created, says Kamen. 

One option is to grow them from scratch out of biological materials like collagen in an environment where pluripotent stem cells — cells that are genetically modified to behave like embryonic stem cells and can form adult cell types — would grow into an appropriate organ.

“And in the really immediate incantation of that, we would introduce pluripotent stem cells from a donor who is going to be the recipient,” explains Kamen.

Creating organs from the recipient’s cells would ideally eliminate the need for immunosuppressant drugs that organ recipients currently need to take to prevent rejection of an organ from a donor — drugs that also have the ability to fight viruses.

The second method is to take a pig’s lung, for example, and — in an extremely simplified explanation — wash off the lung with a version of bleach, stripping off the living cells and leaving a very fine structure of cartilage that stem cells would be introduced into and become a functioning lung. 

“We’re working on two of those things for an incredible company, United Therapeutics, and we were doing it with funding from them and from us,” says Kamen. That is what attracted the Department of Defense to reach out to Kamen to apply for the grant in the first place. 

With the addition of Rockwell Automation to the Manchester Millyard, visits from research and biotech industry giants, and an increase in the caliber of talent applying to the University of New Hampshire Manchester after news broke, Kamen foresees a rebirth of manufacturing in the Manchester Millyard. 

Regenerative medicine would create high-paying jobs and light the fire again under the so-called “New Hampshire advantage,” drawing high-skilled workers to the state, and bringing back home those who have left, says Kamen.

“We’re not going to compete with any of these places doing the basic research, but you search the country, find me the city that’s known for building the industry of creating the organs to solve these problems. And the answer is there isn’t one,” Kamen says. “Why shouldn’t it be here? We have the universities, we have the industry partners. I’ve talked to academics; they want to work with us. We should do it here.”  

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