“Gentlemen, we can rebuild him. We have the technology. We have the capability to make the world's first bionic man.”

Though focused on mechanics, the Six Million Dollar Man serves as a good introduction to the concepts, and promises, of regenerative medicine. 3-D printing could revolutionize engineering, and many speculate that it could have a huge impact on medicine, too. Useful organs grown in the lab three-dimensionally on scaffolds is now closer to fact than fiction. And this, naturally, creates much excitement.

Prizes are already in place for the team that successfully prints a liver, as one example, and transplants it into an animal recipient that survives. Implantable organs might be the most exciting promise, but others, such as producing organs specifically for toxicology studies, might be more practical and provide a greater impact.

The processes and regulatory challenges in taking this technology from the lab to the patient, however, are significant.


Process hurdles

One ultimate goal is mass production of printed organs—thus removing transplant donor waits and minimizing rejection issues. But what happens after tissue printing experiments become accepted treatment options? How will these be taken from the lab to the bed side? No one knows yet. There are no standard process regulations, or even best practices, in place. Some, however, are starting to lay the foundation for automation and, eventually, commercialization— working to take a process that is very expensive and has a low yield and streamlining it to the point where it can be done cheaply and reliably.

North Carolina State University’s Edward P. Fitts Department of Industrial and Systems Engineering (ISE) is one group working to achieve this goal.

“It is one thing to be able to grow an organ but another to take that ability to the bedside, so involving manufacturing engineers early on in the biological research phase is vital to achieving commercialization,” says Dr. Binil Starly, associate professor of regenerative medicine at NC State’s ISE.

Starly’s group is attempting to kick start a program that looks at the manufacturing aspects of regenerative medicine and helps to identify the scale-up issues. ISE identified variability in methods as a crucial issue to be addressed. By tracing the processes and documenting each step, they quickly realized that more standard operating procedure (SOP) was needed.

“When you have humans involved, you’re going to have variability,” says Dr. Ola Harryson, associate professor, Fitts Fellow in Biomedical Manufacturing at NC State’s ISE. “People will do things differently, and that will affect the outcome. So the first thing we tried to do was standardize these processes to reduce the variability in the yield. That was a big step.”

A second concern: quality control. A key element in any automated system is the sensors that ensure the work being done is up to snuff. When you’re dealing with biological processes, these gain even more importance. As Harryson puts it, “you don’t want to keep culturing something that is already out of control.” Unfortunately, the technology is not quite there yet, but it’s getting closer.

“The technology definitely needs to catch up,” says Starly. “I think people are still trying to define what we are trying to sense. Once that can be defined, then sensors can be developed around that.”


Legal challenges

There are a number of legal challenges as well. Chief among these: who gets to hold the patent? Judith L. Toffenetti, Ph.D., partner, McDermott, Will & Emery LLP, points to the example of Dolly— the famous cloned sheep— as one that illustrates the patent issues associated with 3-D bioprinting. A patent on Dolly has been pending for more than 15 years, but was recently rejected.

“The reason the court finally rejected the claims directed to the clone is that there is nothing in the specification that indicates that the cloned animal is any different from the naturally occurring animal,” says Toffenetti. “The claims indicate it’s an identical copy, and therefore, the court found that it is a product of nature.”

Extending this ruling, if one of the criteria for receiving a patent is whether or not the end product is unique or not seen in nature, then a 3-D printed organ is not unique. The goal is, after all, to replicate what is seen naturally.

“Going forward, those who draft patent applications and claims will have to be sure to put in the differences between the naturally occurring and the invented,” says Toffenetti. “Unfortunately, the closer you get to perfection, the further you get from patentability. And 3-D printing is a perfect example of that.”

So what is patentable? The process and methods. Groups similar to Starly’s, that are working to perfect the manufacturing process, stand to have much to gain in this area.

It seems that eventually we will reach a point where the Six Million Dollar Man becomes a reality. What remains to be seen, though, is if that price tag is accurate.