Individually adapted and stable

The goal of the Nano Argovia project CerInk is to develop custom-made bone replacement materials that closely resemble natural bone

 

Agnese Carino, doctoral student at PSI and member of the Nano Argovia project CerInk (M. Fischer, Paul Scherrer Institute)

Humans have over 200 different bones with varying shapes, each of which performs a specific, important function in the body. In the event of bone defects due to accidents, inflammation, or tumors, it is possible to replace the damaged bone – or parts of it – with artificial bone. Given the considerable variations between individual patients and bone types, 3D printing seems the obvious method for producing customized replacement bones. However, optimum bone replacement materials must meet a series of demanding requirements. They must be long-lasting and well tolerated by patients. In addition, they should be lightweight and yet mechanically stable – in other words, they should resemble natural bone as closely as possible. As part of the Nano Argovia project CerInk, scientists from the FHNW School of Life Sciences, the Paul Scherrer Institute (PSI), and the Aargau-based company Medicoat AG worked together closely to develop future bone replacement materials of this kind.

 

Layers with different properties
Human bones are not homogeneous. Rather, they are characterized by a solid outer surface with a dense, mechanically stable (cortical) bone structure, in combination with an internal, sponge-like (trabecular) structure that acts as a sort of shock absorber. The size of these different layers varies depending on the type of bone. This type of multi-layered structure is also desirable in artificial bones that are implanted into patients following accidents or injuries. Scientists from the FHNW School of Life Sciences, the PSI, and the Aargau-based company Medicoat AG have already gained valuable experience in the field of innovative bone replacement materials and have previously combined bioceramic materials with polymers to imitate natural bones using 3D printing. Now, as part of the Nano Argovia project CerInk, they have investigated how the printing process can be used to produce compacted layers with improved mechanical stability. To do so, the scientists added ceramic nanoparticles (nano ink) to the base material. In a subsequent sintering process (which consolidates the artificial bone at high temperature), the nanoparticles bring about a change in density.

Twenty percent is not enough
The team, initially led by Ralf Schumacher (formerly of the FHNW) and later by Dr. Andrea Testino (PSI), used calcium phosphate – the major inorganic component of natural bones – as a scaffolding material for the synthetic bones. They first tested various nano inks with different concentrations of calcium phosphate nanoparticles and biocompatible sintering aids. After some time, it became clear from the experiments that standard print heads can only be used in the 3D printing process if the nano ink contains no more than 20% calcium phosphate nanoparticles. However, this would not allow them to increase the density of the base material to the desired level.

Potato starch to form pores
In the second year of the project, the scientists therefore adopted a different strategy. To find out which nano ink was the most suitable additive, they produced sample pieces from various combinations of materials – without a printing process. This involved combining a calcium phosphate matrix with potato starch, whose purpose was to form pores and to act as a binder. The base materials were ground, dried, and mixed with differing quantities of calcium phosphate nanoparticles, bioglass, and colloidal silica. These sintering aids support the differentiation and multiplication of osteoblasts in the finished bone implant. Finally, the scientists pressed these mixtures into a casting mold. In the first heat-treatment step, they burned the potato starch to create a porous material with the desired initial density. In the subsequent sintering process, the researchers tested three different temperatures between 1,350°C and 1,450°C. In total, they were left with almost 150 different samples, whose mechanical properties and density they analyzed.

A successful approach
The scientists then combined two layers of materials with different composition, carefully selected among more than 5,000 possibilities, to find out how stable the boundary was between the two materials after sintering. As a result, the most suitable combinations, in terms of sintering behavior, density, and mechanical stability for modern bone replacement materials, were identified. Based on morphological analyses using both optical and electron scanning microscopes, the team of researchers established that the chosen approach is promising and could be used to bond two layers together firmly even if they have different densities and mechanical properties.

“In the Nano Argovia project CerInk, we showed that we can produce bone replacement materials that closely resemble natural bone,” says Andrea Testino, the project leader. “In our tests, we were able to produce synthetic bone whose properties correspond to the spongy trabecular structure of bone on one hand and the more-stable cortical structure of bone on the other.” Philipp Gruner, CEO of the industrial partner, Medicoat, also considers the completed Nano Argovia project a success: “Thanks to our project partners’ expertise in this outstanding collaboration, we are in a position to break new ground and develop truly innovative products and technologies for the benefit of patients.”