A novel form of 3D printing, dubbed melt electrowriting, has been used by researchers to produce scaffolds for artificial heart valves that mimic the different biomechanical properties of heart valve tissue. The fabrication platform allows researchers at the Technical University of Munich (TUM) in Germany to combine various, precise custom patterns in the scaffold and fine tune its mechanical properties such that the patient’s own cells will form new tissue as the scaffold biodegrades. The hope is that this technology will produce pediatric implants that will last a lifetime and not require replacement surgery.
Four heart valves in the human body ensure that blood flows in the correct direction, and it is essential that they open and close properly, notes the press release on the TUM website. To fulfill this function, 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 TUM, and Professor Elena De-Juan Pardo from the University of Western Australia, have for the first time imitated this heterogeneous structure by means of melt electrowriting.
High-voltage electric field produces extremely thin polymer fibers
Melt electrowriting is a comparatively new additive manufacturing technology that uses high voltage to create accurate patterns of very thin polymer fibers. As the polymer is melted and pushed out of a printing head in liquid jet form, a high-voltage electric field is applied, which considerably narrows the diameter of the polymer jet by accelerating and pulling it toward a collector. This results in a thin fiber with a diameter typically in the range of five to 50 micrometers. By comparison, a human hair is approximately 70 micrometers. The electric field also stabilizes the polymer jet, which is important for creating defined, precise patterns.
Image courtesy of Andreas Heddergott/TUM
|Close up of scaffold for artificial heart valves printed via melt electrowriting.|
“Writing” the fiber jet according to predefined patterns is conducted using a computer-controlled moving collector. The user specifies the pathway by programming its coordinates.
The researchers have developed software that allows operators to easily assign patterns to different regions of the scaffold by choosing from a library of available patterns. Geometrical specifications such as the length, diameter, and thickness of the scaffold can easily be adjusted via the graphical interface.
Biodegradable medical-grade polycaprolactone (PCL) is used to print the scaffold. After implantation, the researchers believe the patient’s own cells will grow on the porous scaffold, as was the case in first cell culture studies. The cells then potentially would form new tissue before the PCL-based scaffold degrades.
The PCL scaffold is embedded in an elastin-like material that imitates the properties of natural elastin present in real heart valves. The micro-pores in the elastin-like material are smaller than the pores of the PCL structure, leaving the cells enough space to settle but sealing the valves adequately for blood flow, according to the researchers.
Tests showed proper functioning of the artificial heart valves
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, said the press release.
The PCL material was further evolved and evaluated by adding iron oxide nanoparticles, which enabled the researchers to visualize the scaffolds via magnetic resonance imaging. The modified material remained printable and biocompatible. Being able to monitor the scaffolds after implantation could facilitate moving the research into clinical settings.
The ultimate goal of the researchers is to engineer bio-inspired heart valves that support the formation of new functional tissue in patients. This would benefit children, in particular, as current artificial heart valves do not grow with the patient and have to be replaced over the years. “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,” said Mela.
Pre-clinical studies in animal models are forthcoming. The researchers also are focused on further improving the technology and developing new biomaterials.