3D printed, bioinspired heart valves

Development of 3D printed artificial heart valves are designed to allow a patient’s own cells to form new tissue. To form these scaffolds using melt electrowriting – an advanced additive manufacturing technique – researchers created a new fabrication platform enabling them to combine different precise, customized patterns to fine-tune the scaffold’s mechanical properties. Their long-term goal is to create implants for children that develop into new tissue and therefore last a lifetime.

© Andreas Heddergott / TUM | https://www.tum.de

In humans, four heart valves ensure blood flows in the correct direction and it’s essential that heart valves open and close properly. To do this, heart valve tissue is heterogeneous, meaning that heart valves display different biomechanical properties within the same tissue.

A team of researchers working with Petra Mela, professor of medical materials and implants at the Technical University of Munich (TUM), and Professor Elena De-Juan Pardo from The University of Western Australia, have imitated this heterogeneous structure using a 3D printing process called melt electrowriting. They have developed a platform that facilitates printing precise customized patterns and their combination, which enabled them to fine-tune different mechanical properties within the same scaffold.

Precise, customized fiber scaffolds
Melt electrowriting is a comparatively new additive manufacturing technology using high voltage to create accurate patterns of very thin polymer fibers. A polymer is heated, melted, and pushed out of a printing head as a liquid jet to form the fibers.

During this process, a high-voltage electric field is applied, which considerably narrows the diameter of the polymer jet by accelerating it and pulling it towards a collector. This results in a thin fiber with a diameter typically in the range of five to fifty micrometers. Moreover, the electric field stabilizes the polymer jet, which is important for creating defined, precise patterns.

© Andreas Heddergott / TUM | https://www.tum.de

The “writing” of the fiber jet according to predefined patterns is conducted using a computer-controlled moving collector, that collects the emerging fiber along a defined pathway. The user specifies this pathway by programming its coordinates.

To reduce the programming associated with the creation of complex structures for heart valves, researchers developed software to easily assign different patterns to different regions of the scaffold by choosing from a library of available patterns. Furthermore, geometrical specifications such as length, diameter, and thickness of the scaffold can easily be adjusted via the graphical interface.

Scaffolds are compatible with cells and biodegradable
The team used medical grade polycaprolactone (PCL) for 3D printing, which is compatible with cells and biodegradable. The idea is that once the PCL-heart valves are implanted, the patient’s own cells will grow on the porous scaffold, as has been the case in first cell culture studies. The cells might then potentially form new tissue before the PCL-scaffold degrades.

The PCL-scaffold is embedded in an elastin-like material that imitates properties of natural elastin present in real heart valves and provides micro-pores smaller than the pores of the PCL structure. The aim is to leave enough space for the cells to settle, but to seal the valves adequately for blood flow.

The engineered valves were tested using a mock flow circulatory system simulating physiological blood pressure and flow. The heart valves opened and closed correctly under the examined conditions.

© Andreas Heddergott / TUM | https://www.tum.de

Nanoparticles allow
for visualization using MRI
The PCL-material was further evolved and evaluated together with Franz Schilling, professor of biomedical magnetic resonance, and Sonja Berensmeier, professor of bioseparation engineering at TUM. By modifying PCL with ultrasmall superparamagnetic iron oxide nanoparticles, researchers could visualize the scaffolds using magnetic resonance imaging (MRI). The modified material remains printable and compatible with cells. This might facilitate the translation of the technology to the clinics, as the scaffolds can be monitored upon implantation.

“Our goal is to engineer bioinspired heart valves that support the formation of new functional tissue in patients. Children would especially benefit from such a solution, as current heart valves don’t grow with the patient and must be replaced over the years in multiple surgeries. Our heart valves, in contrast, mimic the complexity of native heart valves and are designed to let a patient’s own cells infiltrate the scaffold,” Mela says.

The next step on the way to the clinic will be pre-clinical studies in animal models. The team also works on further improving the technology and developing new biomaterials.