Engineering a healthier Arizona: Fulton researchers tackle urgent health challenges
Five faculty members in the Ira A. Fulton Schools of Engineering are receiving more than $2 million in funding from the Arizona Department of Health Services for research to improve health care in the state. (Left to right) Xiangfan Chen, an assistant professor of manufacturing engineering; Kuei-Chun “Mark” Wang, an assistant professor of biomedical engineering; Mehdi Nikkhah, an associate professor of biomedical engineering; Wanxin Jin, an assistant professor of mechanical and aerospace engineering; and Wenlong Zhang, an associate professor of manufacturing engineering, are pictured against a stylized background of “A” Mountain near the ASU Tempe campus. Image created by Sarah Pierson/ASU
From nanotherapeutics and tissue engineering to stroke rehabilitation and surgical robotics, researchers in the Ira A. Fulton Schools of Engineering at Arizona State University are taking on the health challenges that most affect Arizonans’ daily lives.
The Arizona Biomedical Research Centre, or ABRC, part of the Arizona Department of Health Services, recently awarded more than $2 million to five Fulton Schools faculty members to carry out innovative, community-focused research.
Nanotherapeutic drug delivery targets heart disease
One ABRC-funded effort is focused on developing new tools to combat cardiovascular disease using nanotherapeutic technology.
Before a cardiac event like a stroke or heart attack occurs, the body experiences a buildup of fats, cholesterol and other substances in and on the artery walls. The buildup, known as atherosclerosis, can ultimately block blood flow.
“Atherosclerosis is a precursor to cardiovascular disease,” says Kuei-Chun “Mark” Wang, an assistant professor of biomedical engineering in the Fulton Schools. “It’s the leading cause of death in the entire world and the number one killer in Arizona.”
Wang has carved a niche for himself in the treatment and diagnosis of cardiovascular disease. The ABRC is honoring his research efforts with an Arizona Investigator Grant of $750,000 to develop nanoparticles that mimic those of natural biology for targeted drug delivery to fight arterial plaque in patients with diabetes. Wang is completing the project in collaboration with Zong Wei, a Mayo Clinic researcher specializing in diabetes.
“No simple drug right now can directly target the plaque build-up on the vessel wall,” Wang says. “Every existing form of treatment manages the disease but doesn’t cure it. My team is trying to develop nanotherapeutics that mimic the behavior of white blood cells, which can hone in on the plaque regions and directly send anti-inflammatory medication to those plaques.”
The nanotherapeutic under investigation, a cell membrane-cloaked nanoparticle, involves loading the drug into a nanocarrier that is then coated with white blood cell membranes. Once injected into circulation, the nanoparticle functions like white blood cells, accumulating in the inflamed regions. By doing so, the nanoparticles are readily accepted by the body as a treatment method.
The team has observed positive results in rodent models and is looking to progress to testing in human cells. Wang notes that if proven successful, their therapeutic development could have vast additional applications beyond in patients with diabetes.
“The goal down the line is to incorporate an effective therapeutic agent together with diagnostic agents, known as a theranostic agent,” Wang says. “It could then be used for detecting the disease and releasing the drug locally once there. That way, we can manage disease progression, treatment and outcome with one device.”
A graphic depicts a drug nanoparticle cloaked in a membrane of white blood cells to enable its access to inflamed areas that a white blood cell would naturally gain access to, effectively delivering the drug directly to the inflamed location. Image courtesy of Mark Wang
Tumor-on-a-chip meets nanoparticle drug delivery
In another ABRC-funded project, Wang is a collaborator on a project led by Professor Mehdi Nikkhah, an associate professor of biomedical engineering in the Fulton Schools. Nikkhah has also been honored with an Arizona Investigator Grant and is receiving $750,000 to explore opportunities for camouflaging treatment for drug delivery to cells to personalize cancer treatment.
Nikkhah has a history of successfully modelling the tumor microenvironment on microengineered microfluidic chips, or rectangular pieces of polymers and plastics about the size of a long fingernail with specially designed channels to deposit live cells. The microfluidic chips replicate disease states or organs in an easily controlled environment. Nikkhah has already used this tumor-on-a-chip method to understand the fundamentals of how cancerous cells and their subunits function.
There is currently no treatment for the highly invasive growth of cancerous cells in the brain known as glioblastoma; patients often succumb to the disease within a year of diagnosis. One major challenge in treating glioblastoma is delivering treatment past the blood-brain barrier to reach cancerous cells. The body develops the blood-brain barrier, a tightly locked layer of cells, to defend the brain against hazardous foreign substances. However, this defense also makes the brain effective at preventing various medical interventions.
Nikkhah and Wang realized during a coffee break that applying Wang’s cell membrane-coated drug delivery nanoparticles could be advantageous in Nikkhah’s tumor-on-a-chip model. They will use the ABRC grant to test the efficacy of different medications on individual tumors to determine the best course of treatment.
“Ideally, we will eventually be able to take cells from patients suffering from brain tumors, load the nanoparticle drug into those cells and deliver it to the patient,” Nikkhah says. “This procedure could eventually become a valuable personalized platform.”
An immunofluorescence image shows the migration of patient-derived glioma stem cells in response to drug-loaded nanoparticles within a tumor-on-a-chip platform. Actin filaments, key structural components involved in cell movement and adhesion, are stained yellow. Cell nuclei are labeled in blue. Image courtesy of Mehdi Nikkhah
Suiting up stroke survivors
Whether due to stroke, injury or arthritis, more than 12% of adults in the U.S. have mobility issues, according to the U.S. Centers for Disease Control and Prevention.
“Healthy individuals tend to take things like walking for granted,” says Wenlong Zhang, an associate professor of manufacturing engineering in the Fulton Schools. “People don’t really think about it until they lose the capability.”
The ABRC is awarding Zhang a New Investigator Award of $225,000 to establish soft robotic exosuits that will provide customized support for the lower body mobility challenges of stroke patients.
Zhang’s approach integrates robotic features with conventional fabrics to provide customized stability for its wearer. He and his team are integrating artificial intelligence, or AI, to advance the technology’s capacity to support users and relay information to medical professionals.
The team is collaborating with Dr. Christina Kwasnica, chair of physical medicine and rehabilitation and a brain injury specialist at the Barrow Neurological Institute, and Fabric Tempe, a local nonprofit fashion incubator, to achieve the desired scientific and style criteria. Zhang says that AI and soft robots have a lot of potential to combine with fashion with function to meet a user’s needs.
“This project is a collaboration between engineers, medical professionals and fashion designers,” he says. “When you’re making robots, you typically don’t care too much about how robots look, but we are making something that people may potentially wear every day and be seen using. We want the users to really enjoy the product.”
The researchers have tested prototypes on stroke patients during physical therapy and received overwhelmingly positive feedback. Zhang plans to use the research funding to launch the project past the proof-of-concept stage to establish possibilities for user customization and pave the way to mass production.
“We have been collaborating and exploring completely different types of robots made of softer, more compliant and lower-cost materials to make the product lighter, smaller and easier to wear,” he says. “By developing these robots to be more affordable and effective, we can push this technology into the next stage and one day get it into patients’ homes.”
Wenlong Zhang (right), an associate professor of manufacturing engineering in the Fulton Schools, (right) helps engineering undergraduate student Raj Kodithyala (left) construct a prototype of a robotic exosuit. Photographer: Erika Gronek/ASU
Stimulating tissue engineering
When researchers experiment with neurons in a petri dish, the cells are confined to a flat, two-dimensional surface, similar to a vine plant without a stake or a tomato plant without a cage. This lack of structure has led to an inability to produce functional and dynamic synthetic tissue, creating a major challenge for establishing reliable research models that mimic real tissue and producing synthetic organs.
Xiangfan Chen, an assistant professor of manufacturing engineering in the Fulton Schools, received a New Investigator Award of $225,000 to advance a novel multi-material 3D printing technique that can produce scaffolds with magnetoelectric properties to support the growth of synthetic tissue.
The method stands apart for its capacity to print different materials into one structure that enables new functionalities. Incorporating these features enables researchers to create scaffolds for structural support and nuanced functions, such as generating or manipulating electrical fields, on a scale that can support and stimulate advanced tissue engineering.
“Neuron cells need a certain environment to grow and need to be activated to communicate with each other,” Chen says. “We are creating a 3D printing method to make a scaffold with novel magnoelectric features that provide both structural support and electrical stimulation to promote tissue growth and regeneration.”
Chen is collaborating with Jessica Lancaster, a Mayo Clinic researcher who specializes in age-associated changes in the immune system, to apply his mechanical and manufacturing engineering expertise to biomedical research. Chen notes that if their methods prove successful, there will be significant translational applications for other medical fields.
“My work has always had a multidisciplinary focus,” Chen says. “The tools and techniques developed in an engineering lab can be applied across many domains, including wearable and implantable sensors, neuroscience and synthetic organ production.”
Xiangfan Chen, an assistant professor of manufacturing engineering in the Fulton Schools, printed 2 mm models of the Eiffel Tower using his multi-material 3D printing technique to show the method’s scale and sophistication. Photographer: Erika Gronek/ASU
Advancing dexterity in surgical robotics
Every medical procedural drama depicts surgery as a high-stakes, sweat-inducing and heart-pounding endeavor. Wanxin Jin, an assistant professor of mechanical and aerospace engineering in the Fulton Schools, is improving the skill sets of autonomous robots so it doesn’t have to be.
Jin is incorporating AI into advanced control algorithms to advance the dexterity and safety of autonomous surgical robots, shifting the role of human surgeons from cognitively demanding operators into high-level supervisory roles, only for critical and necessary interventions. The ABRC is providing Jin with a $225,000 New Investigator Award to develop his approach, known as surgeon-on-the-loop, to train robots for certain procedures while surgeons supervise.
“Surgeons are required to keep several factors in mind as they work and make quick assessments for risk that can culminate in mental fatigue,” Jin says. “They need a system that can outsource the assessment to minimize risk.”
Jin is collaborating with Leixin Ma, a Fulton Schools assistant professor of mechanical and aerospace engineering, and Mayo Clinic surgeon Dr. Nitin Mishra to develop the robot’s dexterity to cut, grasp and suture. These tasks may sound simple, but the safety-critical and uncertain physical environment and decision-making demands require a significant amount of assessment on behalf of the robot.
“The robot end-effector tools have to be as flexible, sensitive and dexterous as human hands, which is very challenging,” Jin says. “For now, we want the surgical robot to be able to safely grasp tissue and cut with precision.”
Beyond the surgical domain, the technology could be used in situations that are too dangerous for humans or when a human expert is unavailable.
“It’s more than robotics or AI,” Jin says. “The power is in economics and trust. Taxpayers put their trust in researchers to find ways to improve their quality of life, and they have to trust that our robots will work as promised. Earning that trust is one of my biggest motivations.”
A surgical model is tested in a simulation, shown in the upper right corner, to confirm the dexterity and feedback of Jin’s robot. Image courtesy of Wanxin Jin
