Biomedical engineers in the Cockrell School of Engineering at The University of Texas at Austin have received a three-year, $2.7 million grant from the U.S. Department of Defense (DOD) to advance a promising treatment that could help millions of older Americans and people with diabetes affected by peripheral ischemia, a condition that restricts blood flow to muscles in the lower limbs.
There are more than 3 million reported cases of peripheral vascular disease (PVD) annually in the United States. People over 65 years old, people with diabetes and smokers are most at risk for the condition, which causes peripheral ischemia.
Peripheral ischemia occurs when blockages in arteries or vessels, reduce the supply of blood and oxygen to tissues in the legs and feet. Left untreated, peripheral ischemia can lead to gangrene and amputation. To combat this condition, the UT Austin researchers have developed an injectable, regenerative gel that delivers a combination of sugar-containing proteins called proteoglycans and a growth factor to stimulate the growth of blood vessels and restore blood flow in the lower limbs.
Aaron Baker, associate professor in the Department of Biomedical Engineering, and his research team will receive the funding from the DOD’s Congressionally Directed Medical Research Programs, created to foster novel approaches to biomedical research. The grant will bolster the development of the team’s ischemia treatment and support it through pre-clinical testing to bring the treatment closer to human clinical trials and a commercialized therapy.
Baker is collaborating on the pre-clinical trials with UT Austin biomedical engineering professor Andrew Dunn and Richard Smalling, cardiologist at the McGovern Medical School at The University of Texas Health Science Center at Houston.
“Ischemia is a huge problem for people with diabetes and leads to many issues, including non-healing wounds and the eventual need to amputate limbs, in severe cases,” Baker said. “The purpose of our research is to develop a successful therapy, a gel that can be injected into the leg so blood vessels can grow back.”
Physical therapy, medicine and bypass surgery, which can be performed in the legs to unclog arteries or vessels, can provide temporary relief for patients with severe PVD and the accompanying peripheral ischemia, but there is currently no long-term treatment option.
“Our treatment is different from existing options in that you are going to grow new, small vessels that will take the place of the old ones that aren’t working well,” Baker said.
While there has been great interest from researchers nationwide to deliver growth factors to induce angiogenesis — the growth of blood vessels — other therapies in clinical trials have achieved only limited success in patients.
Baker and his team suspected that these treatments were lacking a key protein that would trigger the growth factors to build blood vessels. During their research, they discovered that diabetic mice were missing proteoglycans, a protein with several sugar chains, which provides signals to the growth factors to grow the blood vessels.
“The idea was to give a growth factor that induces angiogenesis, and also to find the missing piece, proteoglycan, which makes it work,” Baker said.
In experiments, their newly designed therapy successfully grew blood vessels in mice with ischemia and diabetes, and resulted in 85 percent recovery of blood vessels in the mice, compared with 60 percent recovery reported by other growth factor-based treatments. Baker and his team published their work in Advanced Healthcare Materials Feb.18.
“We believe our treatment could also be used as a platform to treat the complications of diabetes, including non-healing wounds and myocardial ischemia, which causes obstructions in the heart,” Baker said.
In the months and years ahead, the research group plans to optimize the treatment and determine the proper dosing and delivery mechanism before moving the patent-pending therapy into human clinical trials.
