It's Alive

Need a jaw replacement in 2015? You’re in trouble. Today’s replacements are designed only to restore mobility, not to alleviate pain. Unlike a knee replacement, a new jaw may or may not actually feel better. And it certainly won’t have a normal range of motion. So far, the complex, two-part movement of the jaw has proven difficult to replicate.

For some patients with jaws that have become fused shut or immobile, the replacement surgery is an unfortunate, even shudder-worthy necessity. As happy athletes with metal alloy, ceramic, or plastic knees skate down the slopes and grandparents with titanium hips take up ballroom dancing, people with jaw pain wonder if surgery might actually make pain worse.

There are a lot of questions about unhappy jaws and what it might take to curb pain in this small, but active joint. One tiny opening amidst a sea of gloomy information is the possibility of a new type of jaw implant – a jaw 3D printed to fit the patient’s face and “seeded” with living cartilage cells to recreate the joint’s function.

Sound futuristic? Not according to TeVido BioDevices' Scott Collins, who says that although seeded implants are a step forward, they’re not the future. In fact, he believes that bioprinting technology – using live cells as ink to print living tissue structures – will surpass the idea of placing living cells on an inorganic structure.

But let’s back up.

We’ve been watching 3D printing slowly transform from a patented technology to a more accessible novelty and, now, a high-tech tool. 3D printers are hardly plug-and-play. Yet many users are lay people – including kids at schools and libraries – but who have the interest and patience to play with smaller models.

Increasingly, we’re seeing products with actual use. Not a mock-up of a mock-up, but something that can be put to work. And perhaps the most newsworthy of these is in the use of medical devices produced on 3D printers. In many cases, the printers are hobbyists. They’re not prosthetists or even print service providers – at least, not at first. They’re people who thought the technology was cool.

Matching Printers with Patients in Need
Jeremy Simon was one of those people. A tech geek, he bought a 3D printer for fun and is now a founding partner of 3D Universe, a 3D printer and materials supplier.

“I became fascinated with the technology and what I could do with it,” he says. So fascinated, in fact, that he soon joined e-Nable. This volunteer-based organization is so new that its 501(c)(3) status was pending when Simon and I spoke, but its model of matching volunteers (who donate printed pieces) with patients in need is quickly gaining momentum.

E-Nable’s model is pretty simple. Patients missing fingers or wrists apply online and e-Nable volunteers match them with 3D printers who guide the process, helping patients take accurate measurements or photos, and then using this data to print plastic pieces for the device. (These aren’t true prosthetics, but devices for simple tasks like grasping, according to e-Nable’s website.)

In some cases, patients may print their own devices, though Simon says this is still less common. Finally, patients also purchase their own nuts, bolts, screws, and padding, then assemble the device following simple instructions.

For Simon, volunteering is a natural fit; many of 3D Universe’s customers come from the community of e-Nable volunteers. He estimates that a quarter or more of his customers are involved with prosthetics. Still, he says he’d love to see prosthetists adopt the technology to create lower-cost, yet higher-tech devices.

“Professional prosthetists create devices using higher quality, higher strength materials,” he says. “But if you want to get a professional, body-powered device, it’s seven to nine thousand dollars. We hope a professional could produce one of these for one to two thousand. We don’t see that as competition. Our goal is to get as many people devices as possible.”

Organizations like e-Nable represent one type of medical 3D device printing, which also extends to surgical drill guides for dental implants, temporary crowns, and more. The industry has gained so much attention that the FDA held a public workshop last October to discuss technical considerations of 3D printing in a forum that included 3D printer manufacturers, device manufacturers, and academics.

Taking Printing to the Operating Room
If there’s a home for current printers in the medical industry, it’s staying on the device side, according to Katie Weimer, VP of medical devices, healthcare, for 3D Systems. An engineer by trade, Weimer joined the print manufacturer through an acquisition just over a year ago. Her division is now one of 3D Systems’ fastest growing.

Weimer specializes in personalized surgery, virtual procedures, and patient-specific technologies. If you need surgery, Weimer and her team could help your surgeon practice the procedure on a model of you, then print the surgical guides doctors would use in the operating room, perhaps even the materials that could be implanted during a joint replacement, for example.

She’s not outsourcing much work just yet, though, even as 3D printing is becoming more common in hospitals. “Most of the history of anatomical models used in healthcare has stemmed from the service industry where they use a service center,” she says. “We have trained biomedical engineers who process data and then print on our printers.” And the company hopes the technology will continue to democratize, with a goal of getting anatomical models into clinicians’ hands for pre-surgical planning. However, Weimer cautions, “There is a difference between printing a medical model for visualization versus something that enters the operating room and must be safe, biocompatible, and sterile.”

At this point, most surgeons learn to use the technology by working with 3D Systems directly through the service-center model. Weimer doesn’t see a shift in that practice coming soon. 3D technology, she says, is just changing too fast. And even companies like 3D Systems, which have the know-how to produce 3D printers, need high-level biomedical engineers like Weimer and her team to enter this field.

And printing is only a small part of what Weimer does. Much of her work is virtual, creating computer models of patient anatomy, processing that data, and helping create anatomical simulations before any printing occurs.

But Weimer says 3D’s impact in medicine has yet to peak. “Everybody has heard a story or two on 3D printing and healthcare, but I don’t think that’s outside of academic institutions or the big surgical centers, I don’t think it’s as widespread.” She says groups like e-Nable are “a great example of the contrast between the type of modeling that’s in use in the operating room versus the lower-level printers that can be used to print cheaply, efficiently, and in durable materials that can be impactful on the patient population. When it comes to healthcare and the medical field, there’s a different level of regulatory requirements.”

Bioprinting: Printing with Cells
“Different level” is an understatement. The level of regulatory oversight in bioprinting – printing living tissues with living substrates, for our purposes – is both staggering and appropriate. As scientists begin to test live tissues that might be implanted into patients, they enter a world tightly regulated by the FDA. University researchers develop the first version of technologies that require millions to commercialize, much like pharmaceutical products.

In fact, some bioprinting is being used to help reduce the cost of developing new medications. At Organovo, company printers aren’t even for sale. Instead, the company acquires or grows cells, converts them into printable materials, and prints them under conditions that allow the cells to survive, then nurtures and feeds the resulting tissue, so that it can develop and differentiate into its final structure.

To be clear, this doesn’t mean they’re pulling organs out of a printer. The company has printed liver, kidney, skin, bone, blood vessel, and lung tissue, to name a few. But the resultant product, while alive, is more paste-like than something you’d find inside a human body. A typical liver tissue print would be about 30 millimeters wide and 1 millimeter tall, according to Michael Renard, Organovo’s executive VP of commercial operations.

So, why print it? First, because there’s a terrific shortage of transplantable organs, and these types of tissues are the first, very early steps toward printing live organs. Secondly, because there is a lucrative market for these tissues.

Take pharmaceutical companies, which spend billions to develop and market medications. Historically, drugs in early stages were tested on cells in petri dishes. But cells are social beings, and each organ has dozens of types of cells. Put the cells together and they begin to communicate, differentiate, and develop differently than they do on their own.

By printing tissues with more – though not all – cell types present in various organs, companies like Organovo create a better testing environment for new medications. For a pharmaceutical company, that means less costly failures (which is where most drug development dollars go) and better predictive abilities. In other words, it’s more likely that cells will act the way they’re expected to in real people in these printed tissues.

And while organs earn the most hype, Renard says his short-term goals are more practical: “There are people out there who could use better medicines and treatments to just live a better or normal life, and we think that’s a new category of care.”

Now you can understand why Organovo isn’t particularly interested in selling or discussing its print technology, and why venture capitalists are increasingly interested in companies like this one.

“I would simply be able to say that the goal is to have a very high percentage [of cells], virtually what you put in, live and survive the process, which means that the printer has to be pretty efficient in terms of speed,” Renard says. “The cells can’t sit on a system for hours and days. They need to be delivered typically under low temperature by comparison to other 3D printing methods with very controlled sheer forces because they are fragile. Think of the difference between printing a golf ball and printing an egg.”

Bioprinting isn’t limited to tissue pastes, however. In Austin, Texas, scientists at TeVido BioDevices are working with skin and fat grafts to engineer implants and grafts for reconstructive surgery or wound care.

Scott Collins, the company’s CTO and VP of research and development, hopes TeVido’s technology will one day be widely used in breast reconstructions. Currently, women who undergo mastectomies may opt to reconstruct their breasts, but technology for rebuilding nipples lags, often involving surgery, healing, and then a tattoo. But colors can fade, and surgical techniques may require tweaking every few years.

Instead, Collins hopes to harvest cells from the patient before they go through the reconstructive process, and then recreate the structure, shape, and color of the lost nipple with a bioprinted implant: “From the tissue engineering standpoint, we’re going to add a vascular layer. Cells need oxygen and nutrients to survive, unlike plastics and metals. Our challenge is to allow things we print to live while they’re being printed and then to survive implantation into humans.” If he’s successful, this technology could help overcome one major hurdle of organ printing – creating blood vessels.

Fat cells don’t do much, metabolically, so building blood vessels to support them is a bit simpler. That’s why Collins has hope for his implants, while organs are still in their infancy.

Whatever happened to our jaw replacement patients, though? Amidst bioprinting and device manufacturing, is there hope in them? Yes and no. 3D technology is poised to make surgeries safer, shorter, and more patient-specific, all of which could be a help. Joints created to match patient anatomy and printed on ever-more-accurate 3D printers with increasingly durable materials could also help. But 3D printing has already been around for decades. Research progress takes time and funding. Even when a technology seems ready, it could take many years to bring it to market, according to Collins.

Yet, Weimer says the most exciting part of this technology in medicine is the change of democratizing it, including patient-specific implants using direct metal printing that offer long-term durability. It’s a sign of hope for the next generation of patients and the physicians that work to heal them.