The biomaterial is based on a hydrogel that Christman’s lab developed. [Image courtesy of UCSD]
Researchers at the University of California San Diego (UCSD) developed a new biomaterial that promotes cell and tissue repair.
The injectable biomaterial reduces inflammation and promotes repair, the UCSD researchers say. Testing proved it effective in treating tissue damage caused by heart attacks in both rodent and large animal models. Researchers also provided proof of concept in a rodent model that the biomaterial could benefit patients with traumatic brian injury and pulmonary arterial hypertension.
Karen Christman, professor of bioengineering at UCSD, and lead researcher on the team that developed the material, said they could begin a study on the biomaterial’s safety and efficacy in human subjects within 1-2 years. The team presented its findings in the Dec. 29 issue of Nature Biomedical Engineering.
“This biomaterial allows for treating damaged tissue from the inside out,” said Christman. “It’s a new approach to regenerative engineering.”
UCSD researchers said no established treatment exists for repairing the damage to cardiac tissue caused by heart attacks. The development of scar tissue can diminish muscle function and lead to congestive heart failure.
“Coronary artery disease, acute myocardial infarction, and congestive heart failure continue to be the most burdensome public health problems affecting our society today,” said Dr. Ryan R. Reeves, a physician in the division of cardiovascular medicine at UCSD Health. “As an interventional cardiologist, who treats patients with coronary artery disease and congestive heart failure on a daily basis, I would love to have another therapy to improve patient outcomes and reduce debilitating symptoms.”
How the UCSD team got here
Christman previously led a team that developed a hydrogel made from the natural scaffolding of cardiac muscle tissue — extracellular matrix. This can be injected into damaged heart muscle tissue via catheter, with the gel forming a scaffold in damaged areas of the heart. That encourages new cell growth and repair.
However, because it must be injected directly into heart muscle, it can only be used a week or more after a heart attack. According to UCSD, any sooner and it would risk damage because of the needle-based injection procedure.
To develop a treatment ready for administration immediately following a heart attack, the UCSD team developed a biomaterial for infusion into a blood vessel. It can be done in a vessel in the heart at the same time as other treatments like angioplasty or a stent. Intravenous injection also represents an option with the biomaterial.
According to the UCSD team, an advantage of the new material comes through even distribution through damaged tissue. This happens because of the infusion/intravenous injection. Hydrogel injected via catheter remains in specific locations without spreading out.
“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,” said Martin Spang, the paper’s first author, who earned his Ph.D. in Christman’s group in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering.
About the biomaterial
According to the researchers, the particle size in the hydrogel posed a problem. It was too big to target leaky blood vessels. So, Spang put the liquid precursor of the hydrogel through a centrifuge to allow for sifting out bigger particles and keeping only nano-sized particles.
The researchers then put the resulting material through dialysis and sterile filtering before freeze-drying. They added sterile water to the final powder, resulting in a biomaterial ready for intravenous injection or infusion into a coronary artery.
In rodent testing, the UCSD team expected the material to pass through blood vessels and into the tissue. However, the biomaterial bound to endothelial cells in blood vessels, closing the gaps developed after heart attacks. This accelerated the healing of the blood vessels, reducing inflammation. Similar results came through in a porcine model.
The team successfully tested its hypothesis that the same biomaterial could target other inflammation types in rodents. These include traumatic brain injury and pulmonary arterial hypertension. The team plans to undertake further preclinical studies for these conditions.
“While the majority of work in this study involved the heart, the possibilities of treating other difficult-to-access organs and tissues can open up the field of biomaterials/tissue engineering into treating new diseases,” Spang said.
Christman and Ventrix Bio — a startup she founded — plan to ask for FDA authorization to conduct a study in humans for the biomaterial. They expect such trials for treating heart conditions to begin in one or two years.