Heart diseases, such as ischemic heart disease, which caused approximately 9.5 million deaths in 2023, have driven researchers to gain a better understanding of how this vital organ works.

One of the most promising approaches is biofabrication, a technique that lets researchers grow cardiac tissue from human cells and replicate some of its functions under controlled laboratory conditions.

Milica Radisic, a researcher at the University of Toronto in Canada, is developing heart-on-a-chip models that can mimic heartbeats, as well as three-dimensional structures that resemble the heart’s ventricles.

“If I want to build functional heart tissue and a functional, basically, whole heart, I want to have something at the centimeter scale that is ejecting fluid,” the researcher said during the International Conference on Biofabrication 2026, held at Tecnológico de Monterrey.

Recreating the Tissues of the Heart’s Complex Structure

However, replicating how the human heart works poses major challenges for tissue engineering, given the complexity of the heart’s muscular structure and the need to coordinate different types of cells.

Radisic’s team developed Biowire, a heart-on-a-chip platform that allows researchers to grow heart muscle cells, known as cardiomyocytes, and stimulate them with electrical impulses to promote their maturation.

“This 6-hertz protocol, which was very aggressive, turned out to be a very potent stimulus for maturation,” she explained. “It’s almost like interval training. If you go to the gym and really push yourself to the limit of your ability, you’re going to build muscle. And that’s what we did in vitro.”

The team also worked on designing three-dimensional structures resembling the ventricles, the chambers of the heart that pump blood to the lungs and the rest of the body.

“Why is this cardiac wringing motion important? Because it enables you to push more blood out of the ventricle. Think about it like if you’re trying to get water out of a towel. How are you doing that? Are you just squeezing, or do you go like this, right? You will like kind of twist as well. So that’s exactly what our heart does.”

Another challenge has been incorporating functional blood vessels into the engineered tissues. To address this, the researchers decided to combine different types of cells, including macrophages, immune cells that play a role in maintaining tissues and supporting their function.

“I know in biofabrication we can build beautiful structures, we can really precisely control structure, and that is critically important, but the cell population is also very important to be able to reproduce some of these biological functions,” the researcher said.

Although the team’s models can already contract and generate pressure, they are still a long way from fully replicating the functions of a human heart.

From Studying Diseases to Testing Drugs

The heart-on-a-chip models developed by the team can also be used to study heart diseases and evaluate how certain medications affect the organ’s function, Radisic said.

One of the applications she has been working on involves studying cardiomyopathies, a group of diseases that affect the heart muscle and can impair its ability to pump blood.

“We work with patient-derived cells to recreate their diseases, such as hypertrophic cardiomyopathy and dilated cardiomyopathy,” she explained. The former causes abnormal thickening of the heart muscle, while the latter weakens its ability to contract.

The researchers analyzed cells from patients and identified the mutations associated with their conditions. They then used gene-editing tools to correct these genetic alterations and developed models of both healthy and diseased cardiac tissue for comparison.

Using these models, the team focused on evaluating how the tissue responds to different substances, including medications.

“So that speaks to safety testing, and this is something that is essentially impossible to pick up in a mouse or rat because mice or rats really don’t rely on this ion channel in repolarization of the action potential,” she explained.

Researchers Investigate Why Cancer Rarely Spreads to the Heart

Radisic has taken her research on cardiac tissue models beyond understanding heart disease and analyzing the effects of medications. She shared findings from a study aimed at uncovering why cancer spreads to the heart far less frequently than to other organs.

“I always ask this question: How many of you know someone who has died of metastasis to the heart? Nobody, or sometimes one person. But if I ask about metastases to the liver or bones, many people will raise their hands. So what’s going on?” the researcher asked the audience. “What is the heart’s hidden shield against cancer?”

The team developed an organ-on-a-chip system that connected breast cancer cells with liver and heart tissues to observe how cancer cells behave when interacting with each type of tissue.

The results showed that cancer cells invaded the liver tissue, while their presence in the cardiac tissue was considerably lower. The researchers also observed that certain substances released by heart cells appeared to hinder the migration of cancer cells.

Genetic and protein analyses also helped identify potential mechanisms behind this protective effect, including the involvement of a protein called ADAMTS9.

“We saw that ADAMTS9, which is a tumor suppressor, is very highly upregulated in cancer cells in the presence of cardiac conditioned media and in the presence of cardiac tissue,” she explained. “When we did that, we found out that indeed if we knock down ADAMTS9, we lose this protection.”

AI and Robotics to Engineer Cardiac Tissue

Toward the end of her presentation, Radisic highlighted advances in the use of artificial intelligence (AI) and robotics to improve the fabrication of human tissues.

Her team uses machine learning tools to analyze multiple combinations of cells and materials, aiming to identify the best conditions for engineering functional tissues.

“Through robotics, we try to automate and either scale down or increase the throughput of production of both organ-on-a-chip systems and these kinds of functional organ models for drug discovery,” she said. “That future is very far away, but you know that cell culture is one of the most tedious parts of lab work. It would be wonderful if parts of this could be automated.”

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