"Cells are highly sensitive" – material development for bioprinting

The big hope of bioprinting is to someday be able to print whole human organs. So far, the process has been limited to testing platforms such as organs-on-a-chip. That's because the actual printing process already poses challenges. For starters, scientists need suitable printing materials that ensure the cell's survival as it undergoes the procedure. The Fraunhofer IGB is researching and analyzing this aspect.

In this MEDICA-tradefair.com interview, Dr. Achim Weber talks about the challenges of bioprinting cells, details the current opportunities of bioprinting, and explains why we still have a long way to go before printed living tissue can routinely help the human body.

Dr. Weber, what are the challenges of bioprinting cells?

Dr. Achim Weber: Cells are highly sensitive and they love their natural environment. This limits us in terms of material selection for the printing process. We cannot print at high temperatures because the cells we normally use in bioprinting are likely to die as a result. You also have to maintain a physiological pH range for many types of cells. This requires us to closely monitor the interaction of the cells with other materials that are used in quality assurance later on. The surface you print on is always a critical factor. Shear stress is another key element as it is part of the bioprinting process when the cells flow out of the nozzle at high speed, which is something not all cells can withstand and survive. You can protect the cells by reducing the printing speed or controlling the shear stress. However, printing at slow speed isn't always beneficial since it might change the bioink composition during the printing process. That's why we need a material that can protect the cells from dying once it is added. Having said that, this process typically always involves some type of cell damage or death.

Which material is suitable for this process? And what are the areas of application?

Weber: We took a closer look at gelatins. As a biomaterial, gelatin can protect the cells during the printing process. Several years ago we researched a substitute material for cartilage. Chondrocytes are the only type of cell found in cartilage, resulting in a relatively simple composition of cartilage. In contrast, entire organs are far more sophisticated since you must provide blood vessels or nerves. That's not the case with cartilage. To bioprint the chondrocytes, we chemically modified the gelatin to enhance its flow and print properties. The combination of chondrocytes and other cartilage material enabled us to bioprint. We incorporated acryloyl group into the gelatin to allow us to cross-link the gelatin scaffold. The liquid structure ultimately solidifies when it is exposed to light. It becomes more solid if you add hydroxyapatite to the ink formulation, allowing us to achieve bone-like structures.

We also adapted material and developed a bioink formulation to print fat tissue. In early 2021, an EU project will launch and emphasize the regeneration of ligament and tendons. Participants include the FC Barcelona professional football (soccer) club and Naturin Viscofan GmbH. Our goal is to develop a material that helps strengthen ligaments and tendons using 3D printing.

What is next for bioprinting? What could it potentially achieve in the future?

Weber: We keep learning new things about the interaction between different materials and living cells. It is highly likely that we will be able to print more complex structures and high-resolution constructs – using more and more types of cells – in the near future. So-called 4D printing is a process that can factor in the full life cycle of cells. At the start of their life cycle, cells need different materials compared to what they require in the middle or at the end stages. Israeli researchers already succeeded in creating a small 3D-printed beating heart made from human tissue. Having said that, it will take some time before we are able to print truly complex biological systems with neural networks and blood vessels.

Why are bioprinted structures so far mostly used as testing platforms versus tissue substitutes?

Weber: You must always be cognizant of the fact that the requirement of the Medical Devices Act must be met when you introduce materials to the body. Yet at this point, there are no regulations for 3D printed (or bioprinted) constructs. How were they tested to make sure they work? That’s a very personalized process that is always unique to the respective person. How do you make sure nothing went wrong during the printing process before the bioprinted tissue is placed inside the body? If you were to test and analyze this aspect, you might destroy the construct or alter it to where it no longer works later on. Who is ultimately responsible for structures and responses? As you can see, we still have to solve several issues from both a regulatory and analytical perspective.