Yet another huge milestone in bioprinting research for our most versatile bioprinting development system has been reached with the study of the scaffold for a tympanic membrane. This is an exciting step toward the bioprinting of complex implantable cartilage structures, a process that is already close to practical applications.
When considering the level of complexity of the various bio-structures in the human body, very few feature the intricate structure and unique functionality of our tympanic membrane (a.k.a. the eardrum). This sparked the interest of Lorenzo Moroni and his team at the MERLN Institute for Technology-Inspired Regenerative Medicine, at the University of Maastricht, to explore the limits of bioprinting using the most advanced equipment available for this task, that is EnvisionTEC’s 3D-Bioplotter®.
The tympanic membrane is a thin membrane that captures vibrations in the air and transforms them into electric signals that our brain can conceive as sounds. If this delicate part of the body breaks, it causes a complete loss of hearing. Being able to reproduce it would have a significant impact in the field of regenerative medicine. However, the complexity of this elaborate task is huge, not only because of the level of miniaturization required (the membrane has a diameter of 15 mm, with a thickness of just 100 micron) but also because of the multiplicity of the tissues involved. The malleus is made up of bone tissue while the membrane has epithelial and neural elements. Recreating it means producing both a physical interface with the malleus and a neural interface with the nervous system.
Lorenzo and his team are currently focused on the 3D printing of the three-dimensional scaffolds that will support the cellular materials. The scaffolds were composed of two FDA-approved copolymers of wide biomedical use and were built using two different approaches. In the first approach, the scaffolds were created by electrospinning (ES) – a particular process in which fine fibres (in this case polylactic coglycolic acid or PLGA) are collected from a liquid using an electrical charge to create a “fiber mat”. In the second approach, ES was combined with 3D printing to produce and three dimensional structures from other copolymers.
ManufacturerSeriesMachine“We 3D print the scaffolds with EnvisionTEC’s 3D-Bioplotter”, Moroni says. “We use polymer-based materials that are biodegradable and bio-compatible. We work to engineer the scaffold’s structural properties as well as those relative to its surface, with the idea that the scaffold will have to interface with stem cells and, let’s say, ‘persuade them’ to undertake a specific type of activity. In this case, what we want is for the cells to differentiate into cells of the otoplastic bone or into the cartilaginous cells of the tympanic membrane. This, for example, can be achieved through a differentiation of the sizes of the pores on the scaffold, which determine the concentration of cell nutrients.”
One of the elements that adds to the complexity bioprinting the tympanic membrane is the fact that the tissue is made up primarily out of collagen. The mechanical properties of this collagen are very hard to imitate and reproduce accurately enough to enable the interface with the malleus to propagate sounds in the frequencies that would be generated on a non-artificial system. Moroni’s team worked in collaboration with a team from the Hospital of Pisa to research ways to organize the collagen fibers in such a way that they will allow the stem cells to display themselves in specific patterns that seem to facilitate the acoustic propagation correctly.
The scaffold that would allow this to take place would be implanted together with the membrane and would progressively dissolve and be absorbed by the newly formed cells. In this case, the material is extruded in the form of a paste with thermoplastic properties, meaning that it is more fluid when hot, and becomes gradually more solid as it cools down. Moroni’s team were among the first to have modified EnvisionTEC’s bioplotter in order to enable the extrusion of plastic materials.
These materials include PCL and PLA; however, one that is now starting to be used more frequently is called polyactive or PA. Other researchers have begun to introduce new co-polymers and other interesting materials such as polymethyl carbonate, that was specifically developed for the printing of soft tissues. The range of available materials has been growing steadily recently and this is not happening by chance. For example, there is a family of polyurethanes that are both biocompatible and biodegradable. They hold a broad range of new possibilities in terms of scaffold development for future bioprinting applications.
This project isn’t the only one led by Lorenzo Moroni. He is also currently working on the printing of pancreatic and neurovascular tissues (capillaries and neural networks together), but no details about those can be revealed yet. At the upcoming Biofabrication 2015 conference, EnvisionTEC will present its latest products and showcase the most exciting new developments in the growing field of bioprinting.
http://envisiontec.com
