There is a special synergy occurring in today’s medical technology landscape. While engineers and biologists have played well together in the past, a new breed of bioengineers is working with scientists to push the envelope even more. Corralling future-forward technologies such as 3D printing, artificial intelligence (AI), and robotics, bioengineers are delivering exciting developments in tissue and cell manufacturing, drug delivery and exploration, as well as medical devices.
Which laboratory-seeded projects have the potential to actively change patients’ and doctors’ lives for the better, and soon? Furthermore, where is bioengineering headed overall?
Cell and tissue manufacturing
3D printing a human heart once sounded like science fiction, but if Adam Feinberg, professor of materials science & engineering and biomedical engineering at Carnegie Mellon University and his team have their way, it will become a reality sooner than you might think. The group recently announced that its lab has developed a technique to 3D print the components of a heart.
However, the debate about whether a functioning, 3D-printed human heart is a month or a decade away remains wide open. In the meantime, bioengineers use cell and tissue manufacturing techniques to chip away at a variety of problems. Keith Cook, professor of biomedical engineering at Carnegie Mellon University, is working on biofabrication of lungs. According to Cook, engineers must figure out how to deliver organ functionality while designing additively manufactured replacements. Doing so would address one of the current challenges in tissue engineering: the inability to take successes accomplished on a micro scale and apply them on a macro scale.
Sometimes this requires altering the approach to thinking and design.
“My lab’s approach is fabricating organs that are completely out of biological tissue but in structures that don’t look like the native organs, so they can be created more easily in a manufacturing process,” Cook says. In essence, a lung does not need to look like a lung to perform its functions.
3D-printed human tissue is gaining traction in bioengineering. Techniques such as laser-induced forward transfer are being reconfigured for bioprinting. However, vascularization remains a significant challenge, according to Dr. Ibrahim Tarik Ozbolat, associate professor at Penn State University.
Ken Church, CEO at nScrypt Inc., which bioprints living material, agrees. “The reality is that when you start getting tissue to a certain level of thickness, there’s a fail point,” he says. “Waste needs to come out, oxygen and nutrients need to be fed. That doesn’t happen effectively, and so you have dead zones.” The good news is that necessary angiogenesis in 3D-printed tissues has already been seen, so the future might still hold hope for fully vascularized organs for the human body.
Then there is cell manufacturing, the basis for successful widespread applications for cell-based therapeutics in cancer treatments. Chimeric Antigen Receptor (CAR)-T cells used in immunotherapy cancer treatments are developed from cells harvested from the patient and weaponized to target cancer cells, according to Thomas Tubon, Ph.D., executive director of the NSF ATE Coordination Network: Advanced Manufacturing for Cell & Tissue-based Products at the School of Applied Science, Engineering and Technology at Madison Area Technical College in Wisconsin.
While CAR T-cell therapy is an example of a successful transition from lab to field adoption, promising cell engineering therapies face issues of scaling up production. Time is another significant challenge because cell production takes at least 12 weeks, a window cancer patients might not be able to afford, according to Tubon. “We can use engineering principles to get that time frame more manageable, to produce cells faster and in a much larger quantity to make them available to patients when they need them,” he says.
Groups such as the Georgia Institute of Technology’s NSF Engineering Research Center for Cell Manufacturing Technologies, the National Cell Manufacturing Consortium, and initiatives led by the Advanced Regenerative Manufacturing Institute and the National Institute for Innovation Manufacturing are helping accelerate progress in the field, Tubon adds. The key to the future in cell-based therapeutics is larger scale, lower cost, and reproducible and engineered processes for medical and other uses.
While much scientific focus is on the printing of living cells in gels, some are developing and using advanced materials that can be repair tissues without needing to add living cells. One company, Dimension Inx, creates advanced, printable materials that become tissue after implementation. Without printing the cells, there is more freedom on the manufacturing side, since these materials can be stored, shipped, sterilized, and used after they are made without worry.
For example, the company’s Hyperelastic Bone material is 90% bio-ceramic. It is a flexible material that the body can recognize and ultimately convert into natural bony tissue on its own—all without using actual living cells in the printing process.
Creative engineering is also solving challenges in drug delivery. Engineers apply technologies such as 3D printing to solve fundamental patient pain points.
Take the example of SPRITAM by Aprecia Pharmaceuticals, a drug used to treat seizures in people with certain types of epilepsy. Some patients with epilepsy may have difficulty swallowing, and SPRITAM delivers a high dose load that rapidly disintegrates with just a sip of water. Typically a high dose load means a very large tablet, according to Jennifer Zieverink, vice president, marketing services at Aprecia Pharmaceuticals, but the company’s proprietary ZipDose 3D printing technology solves that problem.
“With 3D printing, there are no compression forces or dies or molds that are used in a typical tablet press. It allows us to create a drug product in a very porous and loosely compressed form,” Zieverink says. 3D printing distributes the powder precisely and then deposits just enough binding fluid to hold it all together.
Translating the mechanics of 3D printing from one-off production to large-volume manufacturing was a significant challenge. “The print head needs to be extremely precise to have a consistent flow, so a lot of engineering fine-tuning was involved,” Zieverink says.
Robert Langer, institute professor at the Massachusetts Institute of Technology and a major figure in biotechnology, believes the field of drug delivery presents engineers with a variety of challenges: “First you have to decide, ‘Is the patient going to swallow it, are you going to do an implant, an aerosol?’ If you’re going to do a transdermal patch, you have to get the right release kinetics for the medicine. You have to be able to manufacture on a large scale so millions of people can use it,” he says.
Double emulsion techniques, in which droplets of a dispersed substance enclose smaller droplets of another substance, were translated to industry as a way of delivering vital drugs, according to Langer.
Getting the right release kinetics plagued Paul Ashton, inventor of Yutiq and president and CEO of Inflammasome Therapeutics Ltd. Because the drug, fluocinolone acetonide, is released through a tiny implant injected into the eye, the release rate had to be calibrated to deliver just enough medicine to last three years. Yutiq is an example of a drug delivery solution for a very specific challenge: The eye disease posterior uveitis can be potentially blinding, but eye drops do not work for treatment and can cause glaucoma. The trick was to release at a high enough rate to be effective but slowly enough not to cause glaucoma.
Church predicts that biologic drugs are going to be the next frontier in drug delivery advances. The company Koligo, for example, is crafting spheroidal nanoparticles from donor pancreatic cells that can be injected subcutaneously into patients.
“You don’t have to put it in the liver, which is where normally they would do something like this,” Church says. Early studies on mice have shown glucose levels drop from 600 to 120 and stabilize. Biologics can work their way through the human body or stick around and treat diseases such as diabetes.
Engineers are also particularly good at considering form factor, Church says. They know how to think outside the probe. It is why innovative drug delivery techniques, whether through biologics or 3D printing, are the way of the future.
Robotics and AI
Enabling patients to control objects with their brains is part of the future too, as accomplishments by engineers show. Tyler Clites, postdoctoral research fellow at the University of Michigan, has already helped pioneer a new kind of neural interface between machine and human. Through such solutions, amputees who receive a prosthetic leg can preserve the sense of proprioception, which means they can sense where their limbs are in relation to the others. Equally exciting, amputees can control the movement of the prosthetic limb simply by thinking about it.
When an amputee moves their phantom ankle, the electrical system picks up that muscle activity and directs movement of motors on the prosthesis accordingly. It tells the prosthetic foot in which direction to point and with how much force. The surgical component of the interface makes the amputee feel as if their own foot is moving.
A little more than a dozen patients have benefited from this prosthesis and amputation advance, and Clites is looking to target similar progress with arms next. Bin He, trustee professor and department head of biomedical engineering at Carnegie Mellon University, is working to help disabled patients with mind-controlled brain-computer interfaces. With this advance, patients on wheelchairs can perform basic functions such as move the wheelchair and feed themselves.
“We are targeting at helping paralyzed patients who cannot move much but who have clear cognitive states,” He says. “Electrical sensors record what you’re thinking and will generate an intention signal which can control the final result.” This kind of movement was previously achieved using a brain implant, but understandably, patients do not want to have an implant just to move a robotic arm. Instead, the patient would simply wear what looks like a swimmer’s cap with embedded sensors. The sensors are connected to a computerized device which reads signals and connects to the end object that needs to be controlled.
The fields of AI and quantum computing are reshaping medicine in other ways. Quantum computing is accelerating the early stages of the drug discovery process by enabling scientists to rapidly cycle through large molecule configurations to forecast which combinations will work best. The technology is forecast to boost annual operating income for pharma companies by $35 billion–$75 billion.
AI and machine learning are shifting understanding of how neurobehavioral disorders on the autism spectrum are classified and bringing about precision approaches such as those seen in oncology. The AI-driven platform at BlackThorn Therapeutics can find patients within specific “neurotypes” and calibrate treatment goals toward more predictive therapeutic development.
Back to the future
Given the impact today’s advanced technologies have on medical technology, directors of design engineering are poised to make the biggest impact through incremental gains, according to Church.
Industry experts predict robotics, AI, machine learning, 3D printing, and more will translate their basic ideas to engineer better products in service of the patient. Take nanoelectronics in medicine, for example. Tzahi Cohen-Karni, associate professor of biomedical engineering & materials science and engineering at Carnegie Mellon University, expects to see sensors become increasingly miniaturized. “These sensors can measure the electrical activity of cardiomyocytes,” Cohen-Karni says, as a way of gauging heart health under various disease conditions.
Cohen-Karni is working on nanosensors that are unobtrusive enough to not provoke any adverse reactions. “It’s all about fusing electronics with biology,” he says.
That kind of interdisciplinary approach is what design engineers should prepare for. The bottom line, according to Church, is that scientists and engineers need to play well together and solve a real problem in order to most benefit the industry. The technology is the means to an end, not an end in itself.
“The medical industry couldn’t care less what technology you’re using. They just want to solve a problem,” Church says. “If you’re using a 3D printer to solve it, good for you. If you’re using a shovel, that’s fine too. But you have to solve the problem.”
The good news is that the solutions are becoming increasingly elegant. By marrying microfluidics, chemical and bioengineering concepts along with advanced biology concepts, engineers will wow the industry with solutions that solve precise pain points—elegantly.
Written by Poornima Apte