"Spray-On" muscle fibers for biomimetic surfaces

Few patients with heart failure are fortunate enough to receive a donor's heart. Ventricular assist devices (or heart pumps) have been around for several years and are designed to buy time as patients wait for a transplant. Unfortunately, the body doesn't always tolerate these devices. Researchers at Empa now use a new procedure to produce a coating made of cells designed to line the pumps in the future and increase their lifespan.

In this interview with MEDICA-tradefair.com, Lukas Weidenbacher explains how the process his research team developed works, describes where it will be used and illustrates why there is still a long way before a fully implantable artificial heart can be created in the laboratory.

Mr. Weidenbacher, how did you manage to create muscle fibers that grow in multiple layers?

Lukas Weidenbacher: We basically used a combination of two well-known scientific methods. We combined electrospinning, which allows you to create fine synthetic fibers and cell electrospraying. This enabled us to create multilayered constructs made of cells and synthetic fibers. Alternately, layers of synthetic fibers are first created via the electrospinning process and subsequently, muscle fibers are "sprayed" into the pores of the spun scaffold to obtain a hybrid, multilayered construct.

How does electrospraying work exactly? 

Weidenbacher: During this process, we encase the cells with a type of protective capsule made of gelatin. We then use an electric field with positive and negative charge, as we did before during the electrospinning process. With the help of a spraying device, a dispersion with the coated cells is transported into the electric field. The individual liquid particles are subsequently sprayed via the positive charge in the direction of the negative charge. In doing so, they are transported to their destination in the pores of the polymer scaffold. Once there, the gelatin capsule dissolves within minutes. The cells begin to interlace and form elongated muscle fibers, so-called myotubes.

What are the advantages of your process over other methods?

Weidenbacher: One benefit is that thanks to the microfluidic coating, our process prevents cell damage, which can be caused by certain solvents used in the spinning process. The combination of both techniques also gives us spatial control over the cellular distribution in the polymer scaffold. Until now, it was very difficult for tissue engineering to create a mechanically stable 3D construct that contains living cells to use for tissue production. We have now managed to do this with our approach.

Where is this process meant to be used?

Weidenbacher: This process is specifically intended for ventricular assist devices. Our method is meant to imitate the tissue of a human blood vessel, in whose architecture smooth muscle cells are embedded in a fibrillary network, and to eventually line it with a single layer of endothelial cells. This tissue is then meant to form the surface of the ventricular assist device. The interesting part about endothelial cells is that they exhibit the best possible contact properties with human blood. We thus adopt a biomimetic approach where we trick the body into thinking it is not in contact with a synthetic material. A synthetic material could destroy the blood platelets or cause deposits and blood clotting. We aim to improve the hemocompatibility of the pump and avoid these blood clots.

What are your future plans within the scope of the "Zurich Heart" project?

Weidenbacher: Several research groups are involved in the "Zurich Heart" multidisciplinary project. Among them are the ETH Zurich, the University of Zurich, hospitals (called Spital in Swiss) of Zurich and the Heart Center Berlin. Each group is in charge of respective sub-projects. For example, the research groups attempt to add in additional medications into the lining of the devices. In doing so, it would reduce the number of blood thinners patients have to take for instance. Other groups are designing new device geometries to improve blood circulation and thereby causing less damage to the blood. The overall concept is an exciting approach that involves many contributors. Our group has primarily established the method of producing a biomimetic coating. The next step is to test in bioreactors how well the cells adhere to the surface of the ventricular assist device. This is a crucial aspect. If the cells are only loosely attached to the surface, they might get washed away by the blood flow, thus eliminating the protection function.

What are other measures that still need to be taken to create a fully implantable replacement heart in the lab?

Weidenbacher: You can obviously liken this to the quest for the Holy Grail. At this point, it's possible to create individual functional layers – but the actual heart is extremely complex. We would need neural activation and muscle contraction to prompt an artificial heart to beat for example. This is a major undertaking. There are currently various different approaches to accomplish this, though none of them are ready yet for a clinical application. For example, there are approaches where the cells of animal hearts –typically pig hearts- are washed away. You subsequently attempt to insert the patient's cells into the decellularized heart. All of these approaches have great potential but still have a long way to go before application. The ventricular assist devices were already developed several years ago to support heart function and to buy time while you wait for a donor organ transplant. More than ever, we have a lack of donor hearts today. That's why it makes sense to optimize the ventricular assist devices to where they can stay longer in the body.