Understanding artificial bones

Hip and knee joints made of titanium, vertebral bodies made of plastic and other bone implants have already relieved many patients of their pain. However, many wearers of such endoprotheses suffer complications, for example when the artificial bones fail to grow in correctly. “What precisely happens in the body after implantation is still unclear”, says the materials scientist Anne Martin from the Institute for Materials Technology in the mechanical engineering department at TU Darmstadt. Together with her former colleague Markus König and researchers from the biology department led by Bianca Bertulat, she has developed a model system that is intended to simulate the first days after a bone implant has been inserted.

The period after the operation is considered to be of particular importance for the healing process as this is the time when endogenous cells colonise the implant and ideally facilitate its integration into the body. “The surface of the implants plays a key role”, Martin emphasises. By applying a solution that resembles our body fluids the researchers are keen to find out how attractive a surface is for the cells. “Good wetting means the surface and the fluid are compatible.” Wettability depends, among other things, on the structure of the surface and is one of the basic requirements for the deposition of cells. Simply put: Only with a certain roughness cells feel well and develop in the right direction. Therefore, titanium implants are sand-blasted as a standard procedure.

Titanium is the most common material for bone implants. Yet, it is not ideal, since the metal is significantly more rigid than our bones. “If the implant does all the work, the endogenous body tissue in the vicinity is no longer used and degrades”, Martin says. That is possibly a cause for the loosening of endoprotheses. A meanwhile common alternative to titanium are synthetic materials such as PEEK (polyetheretherketone) that have similar mechanical properties as real bones. PEEK implants coated with titanium already exist.

Yet, which implant is best for patients? A clear answer to this question does not yet exist. That was the motivation for the Darmstadt materials technologists and biologists to examine the various materials used for bone replacement more closely. The focus of their joint project is on the interaction between living cells and the surface of implants. For this purpose, the interdisciplinary team has developed a compact testing chamber called SuBiTU (surface biology testing unit) and already registered it for a patent. The chamber is big enough to accommodate circular samples of materials with the diameter of a 2 Euro coin. The samples are exposed to living cells and a nutrient solution. The clever thing about the system: the lid of the chamber has a small glass window through which the cells can be observed with a microscope.

“Our aim with SuBiTU is to map processes that are similar to the body’s own”, emphasises Tom Engler, head of the surface technology competence group at the Institute for Materials Technology. Thus, a perfusion system that continuously supplies the cells with a nutrient likewise body fluids can be connected to the chamber. The influence of blood sugar levels and other parameters could also be examined in this way. Moreover, the biologists have developed a technology that enables the cells in the chamber to grow not only two-dimensionally as in the Petri dish but three-dimensionally as in the human body. Therefore, they apply a drop of collagen to the implant samples.It forms a network on which the cells can orient themselves. “We thus offer the cells not only a meadow but also a house”, Martin says and adds: “Our aim with the realistic tests is to reduce the number of animal experiments.” Until now, there was no possibility of investigating the live interactions between cells and implant surfaces under body-like conditions for a period of several days. All available systems for the microscopy of living cells are simply too small for the examination of implant materials.

For their experiments, the researchers selected specific tissue cells that develop into bone cells under suitable conditions. The hope is that the formation of bone cells occurs in the chamber, initiated by the artificial bone material. To enable this development to be observed, markers were fed into the progenitor cells. Under the fluorescent microscope, they serve as recognition signs for the various cell types.

Some experiments have already been conducted in the new testing chamber. The detailed analysis, however, is still ongoing “At first sight, the cells look good”, Martin thinks. Of particular interest to them is how the structure of the surface of the sample affects cell growth. As PEEK, cannot be sand-blasted, unlike the harder titanium, the Darmstadt materials technologists have developed an embossing method for the creation of rough PEEK samples. They press a stamp made of sand-blasted steel into the heated plastic. Should it turn out that cells on embossed PEEK surfaces grow significantly better than on smooth ones, rough PEEK implants could, for example, in the future be created using 3D printing.

Other modifications are also thinkable. “The surfaces could be designed in such a way that they release substances, which encourage the adhesion of the cells or have an anti-inflammatory effect”, Engler says. A wafer-thin coating of silver, for example, has an anti-bacterial effect whereas certain proteins promote cell growth. Medicines could similarly be anchored to the surface. There are plenty of ideas – and with the new testing chamber, their suitability can finally be tested under body-like conditions.