Some day, heart attack survivors might have a patch of laboratory-grown muscle placed in their heart, to replace areas that died during their attack.
Children born with defective heart valves might get new ones that can grow in place, rather than being replaced every few years. And people with clogged or weak blood vessels might get a new "natural" replacement, instead of a factory-made one.
These possibilities are all within reach, and could transform the way heart care is delivered, say University of Michigan Medical School researchers in the new issue of the journal Regenerative Medicine. Technology has advanced so much in recent years, they write, that scientists are closer than ever to "bioengineering" entire areas of the heart, as well as heart valves and major blood vessels.
But hurdles still remain before the products of this tissue engineering are ready to be implanted in patients as replacements for diseased or malformed structures, the team notes. Among the hurdles: determining which types of cells hold the most potential, and finding the best way to grow those cells to form viable cardiac tissue that is strong, long-lasting and structured at a cellular level like natural tissue.
The new article reviews the current state of cardiac tissue engineering, both at the U-M Cardiac Surgery Artificial Heart Laboratory and in labs worldwide.
"Tissue engineering is a rapidly evolving field, and cardiovascular tissue is one of the most exciting areas but also one of the most challenging," says Ravi Birla, Ph.D., the paper's senior author and director of the U-M Artificial Heart Laboratory. "With this paper, we're presenting the current state of the art as it exists in our lab and others, and pointing out both potential applications and hurdles that remain."
The paper presents a model for collaborative research between engineers, clinicians and biologists for successful cardiovascular tissue engineering research.
"Although there remain tremendous technological challenges, we are now at a point where we can engineer first-generation prototypes of all cardiovascular structures: heart muscle, tri-leaflet valves, blood vessels, cell-based cardiac pumps and tissue engineered ventricles," says Birla.
Research at the Artificial Heart Laboratory has focused on comparing different platforms to engineer functional heart muscle in the laboratory. Last December, Birla and first author Yen-Chih Huang, PhD, published a paper describing their success in growing pulsing, three-dimensional patches of bioengineered heart muscle, or BEHM. That paper describes the use of an innovative technique, using a fibrin hydrogel, that is faster than others, but still yields tissue with significantly better properties.
The gel was able to support rat cardiac cells temporarily, before the fibrin broke down as the cells multiplied and organized into tissue within a few days. Tests showed that the BEHM was capable of generating pulsating forces and reacting to stimulation more like real muscle than ever before.
Previously, the group described the results of a self organization strategy, showing that it was possible to engineer heart muscle that closely resembles normal heart muscle physiology without any synthetic scaffolding material. The U-M team and others have also shown how polymeric scaffolds can be used to engineer heart muscle of any shape or size to match the area of the damaged heart muscle ? raising the possibility of engineering customized patches to meet the specific requirements of patients. All of these approaches are described in the recent review article.
The new article, by Birla and lead author Louise Hecker, a graduate student in the U-M Department of Cell & Developmental Biology, describes the ?bioreactor? that the team uses to grow their BEHM. It also details many other discoveries that have been made by other teams using different cell-growing surfaces and conditions, as well as hurdles that still lie ahead. In all, the authors say, bioengineered cardiac tissue holds immediate promise as a way to study heart disease and its treatment in cell cultures ? and promise over the longer term as a source of new patient treatments.