Bionic heart tissue: U-Michigan part of $20M center Scar tissue left over from heart attacks creates dead zones that don’t beat. Bioengineered patches could fix that.

The University of Michigan is partnering on an ambitious $20 million project to grow new heart tissue for cardiac patients. The new research center has been awarded to Boston University (BU), with strong partnership from U-M and Florida International University (FIU).

“A heart attack creates scar tissue, and the heart never returns to full function. But for every person, we could create a living patch that a surgeon could stitch in,” said Stephen Forrest, who leads the nanotechnology aspect of the project and is U-M’s Peter A. Franken Distinguished University Professor of Engineering. “It’s very audacious.”

The project is a National Science Foundation Engineering Research Center. These 5-year grants are typically renewed for another 5 years, so the researchers are looking at a 10-year timeline to go from the current state of tissue engineering to working, implantable heart tissue.

A heart attack creates scar tissue, but we could create a living patch that a surgeon could stitch in.Steve Forrest

“Heart disease is one of the biggest problems we face,” said David Bishop, director of the new center and a BU professor of electrical and computer engineering and physics. “This grant gives us the opportunity to define a societal problem, and then create the industry to solve it.”

The living patches the researchers are developing would consist of heart muscle cells, blood vessels to carry nutrients in and waste out, and optical circuitry to make the heart muscle cells beat in synchrony. Already, researchers in the lab have been developing ways to structure cells in scaffolds that mimic particular organs and grow blood vessels into artificial tissues. But typically, working implants have been static, biodegradable materials such as artificial windpipes that the body gradually replaces with tissue. Working tissue, like heart muscle, would need to be responsive as soon as it was implanted.

Engineering Research Center grants are extremely competitive, with only four of more than 200 applicants receiving an award in 2017. These centers are designed to work directly with industry to translate breakthroughs along the way out of the lab and into healthcare. Just producing a more true-to-life “heart on a chip” could aid the pharmaceutical industry in developing better treatments for problems such as arrhythmia.

Ramcharan and her colleagues in Lahann’s lab will help design and produce a polymer-protein construct that mimics the 3D matrix connecting the cells in human heart muscle. Heart muscle cells moving into this environment will then be able to link up into a single tissue. Photo: Joseph Xu, Michigan Engineering Communications & Marketing.

In order to produce the heart tissue, the team intends to start with an artificial scaffold that mimics the 3D structure of heart tissue. Joerg Lahann, a U-M professor of chemical engineering, will work with the team building the flexible polymer scaffold, as well as on the attachment and monitoring of cells within that framework.

“Michigan is pleased to lend expertise to the development of implantable heart tissue, which could improve and extend so many lives,” said Alec D. Gallimore, the Robert J. Vlasic Dean of Engineering. “Our faculty members are leaders in nanotechnology and in developing materials that support and interact with living cells and tissues, two areas that are critical to the project’s success.”

The 3D scaffold will initially be peppered with nanometer-sized gold patches that act as attachment points for protein fragments, called peptides, which will then serve as anchors for the cells. They will be printed onto the gold patches using a technique developed by Forrest and Max Shtein, a U-M associate professor of materials science and engineering. This method, called organic vapor jet printing, was initially invented for mass-producing electronic devices.

“The adaptation of this technology to biological systems represents a radically new step,” said Forrest. U-M will receive $2.8 million for these contributions.

Christopher Chen, the center’s director of cellular engineering and a BU professor of biomedical engineering, will lead the effort to grow heart muscle cells on the scaffold and infuse the tissue with blood vessels. Meanwhile, Alice White, director of nanomechanics and chair of the BU mechanical engineering department will work closely with Arvind Agarwal, an FIU professor of mechanical and materials engineering, to produce an artificial nervous system that uses light to synchronize the heartbeat in the tissue.

Stacy Ramcharan, a doctoral student in chemical engineering, uses a computerized system to layer polymer fibers, forming a scaffold for growing cells into artificial tissues. Photo: Joseph Xu, Michigan Engineering Communications & Marketing.

“It’s humbling to have the opportunity to work on something that could really be a game changer,” says Bishop. “If we succeed, we’ll save a lot of lives and add meaningful years for many people.”

In addition to the technical thrusts led by Forrest, Chen and White, Thomas Bifano, a professor of mechanical engineering and director of BU’s Photonics Center, will direct imaging.

Along with the core partners, Harvard Medical School, Columbia University, the Wyss Institute at Harvard, Argonne National Laboratory, the École Polytechnique Fédérale de Lausanne in Switzerland, and the Centro Atómico in Argentina will offer expertise in bioengineering, nanotechnology, and other areas.

Forrest is also the Paul G. Goebel Professor of Engineering, and a professor of electrical engineering and computer science, material science and engineering, and physics. Lahann is also a professor of material science and engineering, biomedical engineering, and macromolecular science and engineering. Shtein is also an associate professor of chemical engineering, macromolecular science and engineering, and art and design. Gallimore is also the Richard F. and Eleanor A. Towner Professor, an Arthur F. Thurnau Professor, and a professor of aerospace engineering.

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Coating method could improve temporary implants that dissolve in the body

A strategy for coating complicated surfaces with biodegradable polymers has been pioneered by a team of researchers led by Joerg Lahann, a professor of chemical engineering and director of the Biointerfaces Institute at U-M. It could enable coatings for implants that dissolve in the body, such as drugs to improve healing.

Permanent polymer coatings are already used on medical equipment that does not biodegrade, such as metal stents that hold blocked arteries open. The drug prevents cells from growing over the webbed metal structure and narrowing the artery again. It can be applied with a technique called chemical vapor deposition – a process that puts the drug into a gas phase and lays it down in an even coating, like fog turning into frost.

“What you couldn’t do until we published this paper is take a suture that biodegrades and coat with a vapor-based coating that would provide similar benefits,” said Lahann. A suture or a biodegradable bone screw might benefit from a coating of growth factors to promote healing, he added.

Other ways of coating include dissolving the drug into a solvent and then spraying it onto the structure. However, the solvents are often toxic, and the spray technique can bridge gaps in open structures or result in one part of a structure blocking the spray from reaching another.

Still, chemical vapor deposition is very tricky with polymers, or chemicals built in a chain – and a biodegradable coating would need to be made out of polymers. Polymers tend to break up when they are vaporized, so they must be built piece by piece onto a surface.

The researchers demonstrated this using two different monomers, or types of links in the polymer chain. By controlling the ratio between the two monomers, and the chemical groups hanging off the sides of the monomers, the team could control how quickly water could get into the polymer and begin breaking up the chain into its nontoxic elements.

In the lab, Lahann’s group is testing out the coating technique with biodegradable scaffolds that they use for implanting stem cells to help heal wounds involving gaps in tissue. They are also beginning a project with the lab of William Giannobile, the Najjar Professor of Dentistry and Biomedical Engineering, to coat biodegradable dental implants with growth factors to speed healing.

Other members of the research team hailed from Northwestern Polytechnical University in Xi’an, China, and the Karlsruhe Institute of Technology in Eggenstein-Leopoldshafen, Germany.

The study was funded the German Science Foundation under the SFB grant 1176 and the Army Research Office (ARO) under Grant W911NF-11-1-0251.

Lahann is also a professor of biomedical engineering, macromolecular science and engineering, and materials science and engineering.

From: Kate McAlpine, Michigan Engineering

Link: http://www.engin.umich.edu/college/about/news/stories/2017/february/coating-method-could-improve-temporary-implants