This groundbreaking biomaterial heals tissues from the inside out

The substance may be administered intravenously and may be used to treat heart attacks, traumatic brain injuries, and other conditions.

An innovative biomaterial that may be administered intravenously lowers tissue inflammation and encourages cell and tissue repair. In both rodent and big animal models, the biomaterial was examined and shown to be helpful in repairing tissue damage brought on by heart attacks. The biomaterial may be helpful to patients with traumatic brain injury and pulmonary arterial hypertension, according to research that also demonstrated proof of concept in a mouse model.

Professor of bioengineering at the University of California, San Diego, Karen Christman was the team's principal researcher and said, "This biomaterial enables for repairing injured tissue from the inside out." It represents a fresh take on regenerative engineering.

Within one to two years, a research on the biomaterial's safety and effectiveness in human subjects might begin, stated Christman. The team, which consists of bioengineers and doctors, revealed their findings in the Nature Biomedical Engineering issue published on December 29.

In the United States, there are reportedly 785,000 new heart attack cases every year. The ensuing damage to cardiac tissue has no proven cure. Scar tissue that forms after a heart attack reduces muscle function and may result in congestive heart failure.

Dr. Ryan R. Reeves, a physician at the UC San Diego Division of Cardiovascular Medicine, stated that coronary artery disease, acute myocardial infarction, and congestive heart failure remain to be the most significant public health issues affecting our society today. "I would want to have another therapy to improve patient outcomes and lessen incapacitating symptoms," says interventional cardiologist who regularly treats patients with congestive heart failure and coronary artery disease.

In earlier research, the team lead by Christman created a hydrogel that can be injected into injured heart muscle tissue through a catheter and is formed from the extracellular matrix (ECM), the natural framework of cardiac muscle tissue. In the heart's damaged parts, the gel creates a scaffold that promotes the creation and healing of new cells. In the autumn of 2019, findings from a productive phase 1 human clinical study were released. However, because it must be injected directly into heart muscle, it must wait at least a week after a heart attack before being utilized. Doing so earlier runs the risk of damaging the heart due to the necessity for a needle-based injection method.

The group's goal was to create a remedy that could be used right away following a heart attack. This required creating a biomaterial that could be injected intravenously or infused into a blood artery in the heart in conjunction with other therapies like angioplasty or a stent.

Martin Spang, the paper's first author, received his Ph.D. from Christman's group in the Shu Chien-Gene Lay Department of Bioengineering. "We sought to design a biomaterial therapy that could be delivered to difficult-to-access organs and tissues, and we came up with the method to take advantage of the bloodstream — the vessels that already supply blood to these organs and tissues," Spang said.

Because it is infused or injected intravenously, the novel biomaterial has the benefit of being equally dispersed throughout injured tissue. In contrast, hydrogel injected through a catheter stays put and doesn't disperse.

How biomaterials are created

The hydrogel that Christman's lab created, which was validated through safety testing to be compatible with blood injections, served as the starting point for research. However, the hydrogel's particle size was too large to specifically target leaky blood arteries. This problem was resolved by Spang, a Ph.D. candidate in Christman's group at the time, by centrifuging the liquid hydrogel precursor, which allowed for the separation of larger particles while retaining only nano-sized ones. Before being freeze dried, the final product underwent sterile filtration and dialysis. The resulting powder is transformed into a biomaterial that may be injected intravenously or infused into a coronary artery in the heart by adding sterile water.

What it does

The biomaterial was then put to the test on a mouse model of heart attacks. Because gaps form between endothelial cells in blood vessels after a heart attack, they anticipated that the substance would flow through the blood vessels and into the tissue.

However, something else occurred. The biomaterial became attached to those cells, filling up the spaces and hastening the blood vessel's recovery, which in turn lessens inflammation. Similar outcomes were obtained when researchers examined the biomaterial in a pig cardiac attack model.

The same biomaterial was successfully evaluated in rat models of traumatic brain damage and pulmonary arterial hypertension to see if it may assist target other kinds of inflammation. For these diseases, Christman's lab will carry out a number of preclinical research.

Next actions

The science of biomaterials and tissue engineering may be able to cure new ailments even though the majority of the work in this study focused on the heart due to the possibility of treating other hard-to-access organs and tissues, according to Spang.

Christman and Ventrix Bio, Inc., the firm she cofounded, want to apply to the FDA for permission to explore the potential uses of the novel biomaterial for treating cardiac diseases in humans. This implies that human clinical trials will start in a year or two.

Preventing left ventricular dysfunction and the development of congestive heart failure is a key reason why we treat severe coronary artery disease and myocardial infarction, according to Dr. Reeves. This simple therapy has the potential to be very important in our therapeutic strategy.