Biomaterials designed to travel through the bloodstream may provide a minimally invasive way to quell inflammation and help damaged tissue repair itself. In animal studies, the injectable substance reversed tissue damage caused by heart attacks in both rodents and large animals. Early proof-of-concept experiments also suggest that the same approach could one day help treat other inflammatory conditions, such as traumatic brain injury and pulmonary arterial hypertension.
“This biomaterial allows us to treat damaged tissue from the inside out,” said Karen Christman, a professor of bioengineering at the University of California, San Diego, and principal investigator on the team that developed the material. “This is a new approach to regenerative engineering.”
The findings were reported as follows: natural biomedical engineering By a team of bioengineers and doctors in 2022. At the time, Christman said human studies testing the biomaterial’s safety and effectiveness could begin within one to two years.
A new route to repair heart damage
Heart attacks remain one of the most serious medical emergencies in the United States, with an estimated 785,000 new cases occurring each year. When blood flow to the heart is blocked, heart tissue can become damaged or die. The body responds by forming scar tissue, but the scar does not contract like healthy heart muscle. Over time, the heart weakens and can lead to congestive heart failure.
Currently, there are no established treatments to directly repair heart tissue after a heart attack. Existing care focuses on restoring blood flow, limiting further injury, and managing the risk of future heart problems.
“Coronary artery disease, acute myocardial infarction, and congestive heart failure continue to be the most vexing public health problems affecting our society today,” said Dr. Ryan R. Reeves, an internist in the Department of Cardiology at the University of California, San Diego. “As interventional cardiac specialists who routinely treat patients with coronary artery disease and congestive heart failure, we are eager to introduce additional treatments that improve patient outcomes and reduce debilitating symptoms.”
From cardiac hydrogels to bloodstream injections
The study builds on Christman’s team’s previous work on hydrogels made from the natural scaffold of myocardial tissue, also known as extracellular matrix (ECM). The gel was designed to be delivered directly to the damaged heart muscle through a catheter. Once in place, they form a supporting structure that promotes cell growth and tissue repair.
Results from a successful phase 1 human clinical trial of that initial hydrogel approach were reported in fall 2019. This trial found that transendocardial injection of VentriGel, a cardiac extracellular matrix hydrogel, is safe and feasible for patients with left ventricular dysfunction after a heart attack, but large randomized studies are needed to test whether outcomes improve.
However, direct injection methods have important limitations. Because it requires a needle injection into the heart muscle, it generally cannot be used immediately after a heart attack. If you deliver it too soon, you risk further injury.
This challenge led researchers to another idea: biomaterials that can be injected into blood vessels of the heart during procedures such as angioplasty or stent implantation, or administered via an intravenous drip.
“We tried to design a biomaterial therapy that could be delivered to organs and tissues that are difficult to access, and we came up with a way to take advantage of the blood vessels, the blood vessels that already supply blood to these organs and tissues,” said first author Martin Spann, a Ph.D. Shu Chien-Gene Lay belongs to Christman’s group in the Department of Bioengineering.
Why IV administration is important
Blood flow-based approaches offer significant practical advantages for biomaterials. Rather than staying at a few injection sites, it spreads evenly throughout the damaged tissue. Therefore, it may be particularly valuable after a heart attack when it is difficult to reach the injury site directly and time is of the essence.
of natural biomedical engineering The study describes the material as an intravascularly injected extracellular matrix biomaterial made from decellularized, enzymatically digested, and fractionated ventricular myocardium. The material was designed to localize to damaged tissue by binding to leaky microvasculature and was largely degraded within about three days.
Biomaterial manufacturing method
To create an injectable version, researchers in Christman’s lab started with a hydrogel they had already developed and tested for compatibility with blood injections. The problem was the size of the particles. The particles in the original hydrogel were too large to effectively target damaged and leaky blood vessels.
Spann solved this problem by processing the hydrogel’s liquid precursor in a centrifuge. This allowed the team to separate out the larger particles and keep only the nano-sized particles. The material was then dialyzed, sterile filtered, and lyophilized. Adding sterile water to the final powder results in a biomaterial that can be delivered intravenously or injected into the coronary arteries of the heart.
How to find damaged tissue
When the researchers tested the biomaterial in a rodent model of heart attack, they expected it to migrate through leaky blood vessels and into damaged tissue. After a heart attack, gaps may form between the endothelial cells that line blood vessels.
Instead, the team discovered something even more surprising. Biomaterials attached to these endothelial cells are thought to help fill gaps and promote blood vessel healing. This process reduced inflammation, one of the main factors in tissue damage after injury.
The researchers then tested the treatment in a pig heart attack model and found similar results. In rats and pigs induced with acute myocardial infarction and subsequently injected intracoronarily, the biomaterial was associated with decreased left ventricular volume, improved wall motion scores, and changes in gene expression related to tissue repair and inflammation.
Possibilities beyond the mind
Although most of the research focused on heart attack damage, the researchers also tested whether the same biomaterial could target other inflamed tissues. The researchers found proof of concept in a rat model that this approach could be useful in traumatic brain injury and pulmonary arterial hypertension.
Its wide range of possibilities is one of the most interesting parts of this work. Many organs and tissues are difficult to access directly, but all are supplied by blood vessels. If biomaterials can use these blood vessels as a delivery route, regenerative medicine may be able to reach injuries that are otherwise difficult to treat.
“Although the majority of the research in this study concerns the heart, it has the potential to treat other organs and tissues that are difficult to access, potentially opening up the field of biomaterials/tissue engineering to treat new diseases,” Spang said.
What has happened since the 2022 survey?
Since that initial study, related research has continued to investigate how extracellular matrix-based biomaterials impact repair after myocardial infarction. 2025 nature communications A study by Christman and colleagues used spatial transcriptomics and single-nuclear RNA sequencing to examine how injectable extracellular matrix biomaterials affect cardiac tissue after myocardial infarction. This study discovered pro-repair signals involved in immunomodulation, vascular and lymphatic development, fibroblast activation, myocardial rescue, smooth muscle cell proliferation, and neurogenesis in a rat model.
Subsequent research did not replace the need for clinical trials of endovascular biomaterials, but added more detailed information about how this class of cardiac extracellular matrix therapy may impact healing at the cellular and local level inside the injured heart.
Ventrix Bio, Inc., a startup co-founded by Christman, also continues to advance related cardiac extracellular matrix technology. The VentriGel listing on ClinicalTrials.gov describes a Phase 1 open-label study in children with hypoplastic left heart syndrome sponsored by Emory University to evaluate the safety and feasibility of intramyocardial injection of Ventrix Bio extracellular matrix material. At the time of access, there was no recruitment yet.
Next steps in human testing
Christman and Ventrix Bio plan to seek FDA approval to study new endovascular biomaterials for human heart disease. If clinical trials are allowed, the treatment must be shown to be safe, practicable, and effective enough to improve patient outcomes.
For now, this treatment remains in the experimental stage. But its appeal is clear. Rather than requiring direct injection into the heart muscle, it could be delivered through existing blood vessel-based procedures or IVs to reach damaged tissue from within.
“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 easily administered therapy could play an important role in our therapeutic approach.”
