Newswise — A new biomaterial that can be injected intravenously, reduces tissue inflammation and promotes cell and tissue repair. The biomaterial was tested and proved to be effective in treating tissue damage caused by heart failure in rodent and large animal models. The researchers also provided proof of concept in a rodent model that the biomaterial could be beneficial to patients with traumatic brain injury and pulmonary arterial hypertension.
“This biomaterial allows for the healing of damaged tissue from the inside out,” said Karen Christman, a professor of bioengineering at the University of California San Diego and lead researcher on the team that developed the material. “This is a new approach to regenerative engineering.”
Studies on the safety and efficacy of biomaterials in human subjects could begin within one to two years, Christman added. The team, which brought together bioengineers and physicians, presented their findings in the Dec. 29 issue of Nature Biomedical Engineering.
There are an estimated 785,000 new heart attacks each year in the United States, and there is no established treatment to repair the resulting damage to cardiac tissue. After a heart attack, scar tissue develops, which reduces muscle function and can lead to congestive heart failure.
“Coronary artery disease, acute myocardial infarction, and congestive heart failure are among the most pressing public health problems affecting our society today,” said Dr. Ryan R. Reeves, a physician in the UC San Diego Division of Cardiovascular Medicine, said. “As an interventional cardiologist, who treats patients with coronary artery disease and congestive heart failure on a daily basis, I want to develop another treatment to improve patient outcomes and reduce debilitating symptoms.”
In previous studies, a team led by Christman developed a hydrogel made from the natural scaffolding of heart muscle tissue, also known as extracellular matrix (ECM), that could be injected into damaged heart muscle tissue via a catheter. The gel forms a scaffold over damaged areas of the heart, encouraging the growth and repair of new cells. Results of a successful Phase 1 human clinical trial were reported in Fall 2019. But because it needs to be injected directly into the heart muscle, it can only be used a week or more after a heart attack – risking damage caused by an injection too soon. – based injection process.
The team wanted to develop a treatment that could be administered immediately after a heart attack. This means developing biomaterials that can be infused into the blood vessels of the heart at the same time as other treatments such as angioplasty or stents, or can be injected by injection.
“We sought to design a biomaterial therapy that could be delivered to hard-to-access organs and tissues, and we came up with a method to take advantage of blood flow — the vessels that supply blood to these organs and tissues,” said. Martin Spang, the paper’s first author, who earned his Ph.D. Shu Chien-Jin Le in Christman’s group in the Department of Bioengineering.
One of the advantages of the new biomaterial is that it is distributed evenly throughout the damaged tissue, because it is infused or injected intravenously. In contrast, a hydrogel injected through a catheter stays in specific locations and does not spread.
How biomaterials are made
Researchers in Christman’s lab started with a hydrogel they had developed, which had been shown to be compatible with blood injections as part of safety trials. But the particle size in the hydrogel was too large to target leaky blood vessels. Spang, then a Ph.D. A student in Christman’s lab solved this problem by putting the hydrogel liquid through a centrifuge, which allows the larger particles to be removed and only the nano-sized particles to be retained. The resulting material was put through dialysis and sterile filtering before freeze drying. Addition of sterile water to the final powder results in a biomaterial that can be injected intravenously or inserted into the coronary artery of the heart.
How it works
The researchers then tested the biomaterial in a rodent model of heart failure. They expected this material to move into blood vessels and tissues because gaps develop between endothelial cells in blood vessels after a heart attack.
But something else happened. The organic material binds to those cells, closing the gaps and accelerating the healing of the blood vessels, thereby reducing inflammation. The researchers also tested the biomaterial in a porcine model of heart failure, with similar results.
The team also successfully tested the hypothesis that the same biomaterial would help target other types of inflammation in mouse models of traumatic brain injury and pulmonary arterial hypertension. Christman’s lab will conduct several preclinical studies for these conditions.
“While much of the work in this study involves the heart, the possibilities of treating other hard-to-reach organs and tissues could open up the field of biomaterials/tissue engineering in the treatment of new diseases,” Spang said.
Meanwhile, Christman, along with Ventrix Bio, Inc., a startup he co-founded, plans to seek authorization from the FDA to study the new biomaterial’s applications for heart conditions in humans. That means human clinical trials start in a year or two.
“One of the main reasons we treat severe coronary artery disease and myocardial infarction is to prevent progression to left ventricular dysfunction and congestive heart failure,” Dr. Reeves said. “This easy-to-administer therapy has the potential to play an important role in our treatment approach.”