Tissue engineering advance reduces heart failure in model of heart attack

January 26, 2017 by Jeff Hansen, University of Alabama at Birmingham
Heart cells growing in rectangular, box-like scaffold made with 3-D printing. Credit: University of Alabama at Birmingham

Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer. The cells organized themselves in the scaffold to create engineered heart tissue that beats synchronously in culture. When the human-derived heart muscle patch was surgically placed onto a mouse heart after a heart attack, it significantly improved heart function and decreased the amount of dead heart tissue.

"Our novel technique is the first to achieve resolution of 1 micrometer or less," the researchers reported in the journal Circulation Research. This tissue engineering advance is an important step toward the goal of preventing failure after a heart attack. Such heart failures account for nearly half of the 7.3 million worldwide heart disease-related deaths each year.

The heart cannot regenerate after a heart attack has killed part of the muscle wall. That dead tissue can strain surrounding muscle, leading to a lethal heart enlargement. It has long been the dream of heart experts to create new tissue that could replace damaged muscle and protect the heart from dilatation after a .

The researchers, led by Jianyi "Jay" Zhang, M.D., Ph.D., the University of Alabama at Birmingham, and Brenda Ogle, Ph.D., the University of Minnesota, modeled the scaffold after a three-dimensional scan of the of a piece of mouse myocardial tissue. Extracellular matrix is the collection of compounds secreted by cells that gives structural support and cushioning to hold the tissue together.

Using multiphoton three-dimensional printing, the team then created crosslinks among extracellular proteins dissolved in a photoreactive gelatin. When the uncrosslinked gelatin was washed away, the photopolymerized extracellular protein scaffold that remained replicated the shape of the extracellular matrix, with hollows where cells had been.

This native-like scaffold was seeded with a mix of 50,000 cardiomyocytes, and endothelial cells derived from human-induced , or hiPSCs. This cardiac muscle patch, about four one-thousandths of an inch thick and eight one-hundredths of an inch square began beating within one day of seeding, and the speed and strength of contractions increased significantly over the next week.

Researchers found that the scaffold had aligned the muscle cells properly, similar to native , and the cells showed a smooth wave of electrical signal moving across the patch, a vital part of the electrophysiology that propagates contraction of the heart across the atria or ventricles. It appeared that the native-like structure of the scaffold contributed to the healthy electrical and mechanical function of the .

When two of the patches were transplanted onto an infarcted mouse heart, there was significant improvement in measures of cardiac function, blood vessel density and cell proliferation, and reduced infarct size and programmed cell death, or apoptosis.

"Thus, the hiPSC-derived cardiac muscle patches produced for this report may represent an important step toward the clinical use of 3-D-printing technology," Zhang, Ogle and colleagues wrote. They also said, "To our knowledge, this is the first time modulated raster scanning has ever been successfully used to control the fabrication of a tissue-engineered scaffold, and consequently, our results are particularly relevant for applications that require the fibrillar and mesh-like structures present in cardiac ."

Explore further: Challenges of custom-engineering living tissue to fix a heart

More information: Ling Gao et al. Myocardial Tissue Engineering With Cells Derived from Human Induced-Pluripotent Stem Cells and a Native-Like, High-Resolution, 3-Dimensionally Printed Scaffold, Circulation Research (2017). DOI: 10.1161/CIRCRESAHA.116.310277

Anton V. Borovjagin et al. From Microscale Devices to 3D Printing, Circulation Research (2017). DOI: 10.1161/CIRCRESAHA.116.308538

Related Stories

Challenges of custom-engineering living tissue to fix a heart

June 8, 2016
Jianyi "Jay" Zhang, M.D., Ph.D., brought his biomedical engineering expertise to the University of Alabama at Birmingham to fix hearts.

Scientists create heart cells better, faster, stronger

November 10, 2016
Scientists at the Gladstone Institutes identified two chemicals that improve their ability to transform scar tissue in a heart into healthy, beating heart muscle. The new discovery advances efforts to find new and effective ...

Researchers develop spring-like fibers to help repair damaged heart tissue

September 23, 2013
The threat from a heart attack doesn't end with the event itself. Blockage of blood flow to the heart can cause irreversible cell death and scarring. With transplants scarce, half the people who live through a heart attack ...

Muscles on-a-chip provide insight into cardiac stem cell therapies

February 8, 2016
Stem cell-derived heart muscle cells may fail to effectively replace damaged cardiac tissue because they don't contract strongly enough, according to a study in The Journal of Cell Biology. The study, "Coupling Primary and ...

Functional heart muscle regenerated in decellularized human hearts

March 11, 2016
Massachusetts General Hospital (MGH) researchers have taken some initial steps toward the creation of bioengineered human hearts using donor hearts stripped of components that would generate an immune response and cardiac ...

Recommended for you

New cellular pathway helps explain how inflammation leads to artery disease

June 21, 2018
Investigators have identified a new cellular pathway that may help explain how arterial inflammation develops into atherosclerosis—deposits of cholesterol, fats and other substances that create plaque, clog arteries and ...

'Smart stent' detects narrowing of arteries

June 19, 2018
For every three individuals who have had a stent implanted to keep clogged arteries open and prevent a heart attack, at least one will experience restenosis—the renewed narrowing of the artery due to plaque buildup or scarring—which ...

Marriage may protect against heart disease / stroke and associated risk of death

June 18, 2018
Marriage may protect against the development of heart disease/stroke as well as influencing who is more likely to die of it, suggests a pooled analysis of the available data, published online in the journal Heart.

Deaths from cardiac arrest are misclassified, overestimated

June 18, 2018
Forty percent of deaths attributed to cardiac arrest are not sudden or unexpected, and nearly half of the remainder are not arrhythmic—the only situation in which CPR and defibrillators are effective—according to an analysis ...

Tick-borne meat sensitivity linked to heart disease

June 15, 2018
University of Virginia School of Medicine researchers have linked sensitivity to an allergen in red meat—a sensitivity spread by tick bites—with a buildup of fatty plaque in the arteries of the heart. This buildup may ...

The molecules that energize babies' hearts

June 14, 2018
A metabolic process that provides heart muscle with energy fails to mature in newborns with thickened heart walls, according to a Japan–Canada research team.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.