Following a heart attack, there is development of scar tissue, which affects muscle function and can result in congestive heart failure. However, there is still no established treatment available for repairing the damage caused to cardiac tissue after a heart attack. Now, a newly-developed biomaterial that can be injected intravenously reduces inflammation in tissue and encourages cell and tissue repair. Researchers who developed the biomaterial also tested it and proved its effectiveness in treating tissue damage as a result of heart attacks in rodent as well as large animal models. They also provided proof of concept in a rodent model that the biomaterial may benefit patients with traumatic brain injury and pulmonary arterial hypertension.

In previous studies, a team of bioengineers and physicians at the University of California San Diego (La Jolla, CA, USA) had developed a hydrogel from the natural scaffolding of cardiac muscle tissue, also known as the extracellular matrix (ECM). This gel can be injected into damaged heart muscle tissue using a catheter and forms a scaffold in the damaged areas, promoting new cell growth and repair. The researchers had reported successful results from a phase 1 human clinical trial although the gel can only be used a week or more after a heart attack as it has to be injected directly into the heart muscle – risking damage caused by the needle-based injection procedure. This time, the team set out to develop a treatment that could be administered immediately after a heart attack. For this purpose, the team developed a biomaterial that could be infused into a blood vessel in the heart at the same time when other treatments such as angioplasty or a stent were being administered, or injected intravenously.

The researchers began with the hydrogel they had developed, which had proved to be compatible with blood injections in safety trials. However, the particle size in the hydrogel was too large to target leaky blood vessels. The researchers resolved this issue by putting the liquid precursor of the hydrogel through a centrifuge, enabling them to sift out bigger particles and retain only nano-sized particles. The resultant material was made to go through dialysis and sterile filtering before being freeze dried. After the addition of sterile water to the final powder, a biomaterial is obtained that can be injected intravenously or infused into a coronary artery in the heart. The new biomaterial offers the advantage of even distribution throughout the damaged tissue, as it is infused or injected intravenously. In contrast, hydrogel injected using a catheter stays in specific locations and does not spread out.

The researchers went on to test the biomaterial on a rodent model of heart attacks. The material was expected to pass through the blood vessels and into the tissue due to the development of gaps between endothelial cells in blood vessels after a heart attack. However, the researchers found that the biomaterial instead bound to those cells, closing the gaps and accelerating healing of the blood vessels, as a result of which inflammation was reduced. Testing the biomaterial in a porcine model of heart attack generated similar results. The team also successfully tested the hypothesis that the biomaterial could help treat other types of inflammation in rat models of traumatic brain injury and pulmonary arterial hypertension. The researchers will now undertake preclinical studies for these conditions with a study on the safety and efficacy of the biomaterial in human subjects expected to begin within one to two years.

“This biomaterial allows for treating damaged tissue from the inside out,” said Karen Christman, a professor of bioengineering at the University of California San Diego, and the lead researcher on the team that developed the material. “It’s a new approach to regenerative engineering.”

“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. “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.” 

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