3D-Scaffolds: "You can use all structures to create all kinds of implant geometries"

Using 3D lithography via two-photon polymerisation of biodegradable copolymers, 3D scaffolds with substructures on a micrometre scale were produced for the first time. The process will open up new possibilities in the therapy of cartilage-bone defects. We talked to Dr. Klaus Liefeith about the topic. 

Prof. Dr. Liefeith, how do you create 3D printed scaffolds?

Prof. Dr. Klaus Liefeith: We use a special maskless 3D printing technique pertaining to a 3D nanolithography system that is based on the multi-photon absorption principle. This means, we use a structuring process that addresses photochemically sensitive polymers. Polymerization only takes place inside the focus of the laser beam and is therefore – macroscopically speaking – reduced to one point. Moving the laser focus leaves a trace of polymerized material wherever it is guided via computer. The material is subsequently built up layer by layer so that respective structures can be programmed. In this way, a polymer is cross-linked to form a solid structure. The nice thing about it is that this works without expensive masks: You can use all structures that can be mathematically processed and create all kinds of implant geometries.

What materials are used in this setting?

Liefeith: The research is part of the ProMatLeben initiative, which was launched by the German Federal Ministry of Education and Research (BMBF) a few years ago. The project aims to replace biopolymers with lactic acid components (polylactides and polyglycolides). Corresponding studies have shown that these types of polymers form acidic degradation products when they break down in the body. While the reaction products themselves are not toxic, the degradation process produces a very low pH, resulting in necrosis in the tissue surrounding the implant. To prevent this from happening, the ProMatLeben initiative was designed to develop alternative biopolymers that no longer exhibit these effects.

We developed an amide-caprolactone polymer and compared it with lactide-caprolactone (which contains the undesirable lactide): The amide-caprolactone polymer no longer formed the acidic degradation products – the new implant structures are written with this polymer platform.

Which diseases could be addressed with this process?

Liefeith: The process should also be considered as an approach for diseases that go beyond the scope of bone-cartilage defects. Our Institute is in the process of creating all kinds of disease models. That means, on the one hand, we are targeting diagnostics: To generate three-dimensional cell cultures on a chip, you need an artificial matrix that we write using two-photon polymerization. These matrices are then populated with cells, creating a three-dimensional tissue structure that allows us to map out better and more physiologically adequate studies compared to the previously applied standard 2D cell culture systems.

We also target various therapeutic aspects of tissue engineering: We team up with the University Medical Center Göttingen to produce corresponding implants that are placed in the jawbone. There are also other conceivable approaches such as skin replacements. Basically, tissue engineering always requires the respective scaffolds to support cell regeneration – you can use this process to manufacture them with a high degree of flexibility.

When do you expect this research to be ready for the market?

Liefeith: It seems possible to make these implants under commercially viable conditions. It used to take us several days to write an implant. Thanks to industry partners who are also involved in the project, it now only takes one and a half hours.

Of course, there are several technical capabilities that will allow us to further upscale the process. Diffractive optical elements (DOE) make it possible to split the laser beam, enabling you to write with not just one but with eight or 16 beams. This means you can increase your speed for periodic structures by a factor of 16 in one fell swoop. At some point there might also be newer photoinitiators that are faster, resulting in a faster polymerization reaction. As you can see, there are many ways to make this process even more attractive.

What’s your opinion: How will 3D printing continue to change the medical landscape?

Liefeith: I think we are still in the early stages, but I know there are still many interesting possibilities to explore. There are phenomenal growth prospects from our perspective, running the gamut from electrospinning, two-photon absorption to 3D printing. I believe that 3D printing has big advantages over traditional manufacturing processes. I am confident that sooner or later it will conquer other parts of the industry as well.