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Photograph by C.J. Burton/Corbis
For the more than 21 million Americans with osteoarthritis, just going about their daily routines can cause debilitating pain and suffering. Though drugs or complicated operations to repair the underlying joint damage are options for the worst cases, there is no cure. But what if the patient’s body could heal itself?
Bioengineering Professor Liping Tang believes such treatment is possible. He is one of several UT Arlington engineering professors developing health-related innovations that take advantage of the body’s amazing ability to protect and heal itself. Early successes have brought millions of dollars in support from federal sources and interest from private companies.
Dr. Tang’s team, which includes collaborators from UT Southwestern Medical Center and Texas Health Arlington Memorial, focuses on what’s called post-traumatic osteoarthritis (PTOA), which accounts for about 10 percent of osteoarthritis cases. It stems from the improper healing of injuries and is increasingly common in young military veterans.
With help from a $1.04 million U.S. Army grant, Tang will use biologically based microscaffolding and nanoparticles manufactured in his lab to arrest the ongoing cartilage damage that leads to osteoarthritis. The goal is to attract stem cells from elsewhere in the body to do the healing.
With Kytai Nguyen's nanoscaffold, the heart can heal itself.
“Once the cartilage cells start dying because of injury, that usually causes erosion of the substrate. Everything starts to die more and more, which is how the osteoarthritis starts,” Tang explains. “That’s why we want to introduce the stem cells. The stem cell has a unique function of reducing inflammatory response. So the first thing it would do is stop the further damage, then it would be able to help with regeneration.”
Doctors have used scaffolding for years to successfully promote healing inside the body for larger defects such as broken bones. But the thin layer of cartilage that is vital to the proper functioning of joints requires a more minuscule approach. And that’s where Tang and his collaborators are concentrating.
In 2014, Tang and Joseph Borrelli, an orthopedic surgeon at Texas Health Arlington Memorial, published a paper in the prestigious online journal PLOS One detailing the successful creation of a “mini-bioreactor” to regenerate bone tissue inside the abdomen of a laboratory mouse. For their osteoarthritis research, the researchers are now working to identify the biomolecular protein that prompts the best response from stem cells to jumpstart healing and regeneration. They’ll then attempt to duplicate it in the lab.
Dr. Borrelli believes the cartilage regeneration project could benefit young sufferers of PTOA, who could be facing a lifetime of pain.
“Stimulating the body’s own reparative mechanisms for these acute cartilage injuries, as proposed in our new research, could prevent the development of PTOA,” he says. “It would represent a unique and powerful method to treat this life-altering condition.”
Success will also mean a huge step forward for tissue regeneration research, much of which has previously been confined to removing tissue and stem cells from the body and doing the regrowth in a lab before reinsertion.
“We think if a cell can do the work inside the body instead of taking it out and doing everything in the lab, it would make the whole process a lot easier,” Tang explains. “The body is a good bioreactor. What it needs is direction, which we provide with the microscaffolding.”
Figuring out the behavior of beneficial stem cells also could help researchers better understand so-called cancer stem cells, which leave a tumor and spread through the lymph nodes and other parts of the body when a cancer metastasizes. Tang is working to develop artificial lymph nodes that would use targeted proteins to attract the cancer stem cells, then trap and destroy them. For this project, he is collaborating with Jer-Tsong Hsieh, the Dr. John McConnell Distinguished Chair in Prostate Cancer Research at UT Southwestern.
Their overall goal? To help doctors more effectively treat diseases.
Like Tang, mechanical and aerospace engineering Professor Haiying Huang believes the input of medical professionals is essential to her health-focused research. In fact, one of her most promising projects might not exist without it.
Several years ago, Dr. Huang’s team developed wireless sensor technology to monitor stresses and cracks in aerospace structures. Afterward, Fan Gao, an assistant professor at UT Southwestern, contacted her to see if she could adapt the technology to help patients with amputations. A specialist in orthotics and prosthetics as well as orthopedic biomechanics, Dr. Gao has seen the pain that can result from a poor fit between an amputee’s residual limb and the prosthetic socket.
Haiying Huang's new prosthetics can adapt to the wearer.
“The tissue pushes against the socket, and with that pushing you have stresses between those two surfaces,” Huang explains. “Right now, there’s really no sensor that can measure these stresses, but it’s important to do so because if you don’t control them, they can cause ulcers and other skin problems for the user.”
Previously, commercially available gel pads or even balled-up socks were often the only ways to relieve the pressure caused by physical activity and natural day-to-day changes in a residual limb’s shape. But Huang and Gao, along with Muthu Wijesundara, a principal research scientist at the UT Arlington Research Institute, are collaborating on a system that places sensors in a liner commonly used by amputees to regulate and control those stresses.
About the size of a dime, the sensors measure shear (up-and-down) stress and pressure at the interface between the socket and residual limb. When coupled with a grid of bubble-like inflatable padding developed by Dr. Wijesundara’s team, the system will be able to react to information from the sensors by inflating and deflating its padding to relieve irritation and provide extra support.
Realizing the work’s potential to help service members returning from war, the Department of Defense Peer Reviewed Orthopaedic Research Program awarded the team a $744,300 grant in 2014. That same year, a Congressional Research Service Report estimated that U.S. troops fighting in Iraq and Afghanistan from 2001 to 2014 had undergone more than 1,500 major limb amputations.
Liping Tang is recruiting stem cells to treat osteoarthritis.
“The technology is not the hurdle. The hurdle is how you couple the technology with the medical side because there is not much data,” Wijesundara says. “Everyone knows the problem but not necessarily how to tackle it.”
Wijesundara believes this type of dynamic interface has a variety of additional applications, from seating pads for wheelchair users to hospital bed liners.
“This research will not only help patients by making their prosthetics more comfortable, but will also provide a huge database that will help us understand how skin ulcers relate to different variables,” Huang says. “Right now, nobody knows the exact causes of skin ulcers because there is no data. Science and engineering research is all based on data. Without it, all we have is speculation.”
Finding reliable data isn’t much of a problem for researchers when it comes to the risks associated with angioplasty. The procedure, sometimes referred to as balloon surgery, clears narrowed arteries caused by coronary heart disease without a risky bypass. But the balloon usually damages the vascular endothelium cells lining the arterial wall. This damage can expose the inflamed sub-endothelium to blood flow, thus triggering a series of inflammatory responses that results in the artery becoming clogged once again, a condition known as restenosis.
Typically, a stent, or mesh metal tube, is placed inside the artery to support the arterial wall and prevent restenosis. But even with it, patients run a two in 10 risk of the artery becoming blocked again, according to the National Heart, Lung, and Blood Institute. If that happens, the stent can make it impossible to repair the damaged section with the same treatment.
Bioengineering Professor Kytai Nguyen and Aneetta Kuriakose, a doctoral student in her lab, hope their work results in a more natural and effective solution. They are collaborating with Tang and professors from UT Southwestern and Penn State University to create a multifunctional nanoscaffolding that would line the injured endothelium after angioplasty.
“We want to let the arterial wall heal by itself,” Dr. Nguyen says. “If the body heals by itself, then you don’t have to put anything permanent in there, like a stent. So if you want to open the artery up again, you still can.”
The nanoscaffolds are equipped with agents that can capture stem cells in blood circulation. Those trapped stem cells eventually will mature into endothelial cells, which make up the endothelium.
“What we’re trying to do is to re-create that endothelial barrier,” Kuriakose explains. “If there is a good barrier, it prevents the exposure of that sub-endothelium and therefore restenosis doesn’t happen.”
Nguyen’s team used a grant from the American Heart Association to develop a proof of concept that was published in the 2014 edition of the American Chemical Society’s journal, Nano. That led to a four-year, $1.4 million National Institutes of Health grant.
Project collaborator Subhash Banerjee believes that this work has great potential benefits for patients. He is a professor of medicine at UT Southwestern and chief of cardiology at the VA North Texas Health Care System at Dallas.
“Our research is patient-centric, and the use of technology to improve quality of life for our patients is the ultimate objective of all our research efforts,” he says. “It is the driving force that keeps us going.”
