How do human cells respond to biomaterials? And how can the interaction be further improved? Geistlich traces these questions in its cell laboratory.
The human body, taken at a cellular level, has long ceased being the closed village community that it was once considered to be. In 1890 Themistocles Gluck fitted the first artificial knee joint in Berlin. Since then, foreign matter within the body has become almost a matter of routine.
There are now 950,000 artificial hip and knee joints implanted each year, just in Europe. To this can be added 6 million dental implants, 2 million of which are accompanied by bone replacement augmentation.
An entire arm of research is now concerned with perfectly integrating biomaterials into human tissue. How do cells respond to the impostor? How can integration be made better, faster and with fewer complications? At Geistlich Pharma’s research site in Wolhusen, a research team is dedicated to these questions. Seven biologists are currently working on investigating the precise interactions between somatic cells and Geistlich biomaterials. Research group leader Dr. Paul Buxton explains to us why this cell research is important.
Geistlich has its own laboratory for testing how cells react to our products. For what exactly are you looking?
Dr. Buxton: We test, for example, different variants of a new bone replacement biomaterial, or we vary specific parameters in the production of Geistlich Bio-Oss®. The key question then is: how does the new product affect the bone-forming cells? What variant best promotes osteogenesis?
Dr. Buxton: Precisely. Cell tests make it possible for us to compare biomaterials at a very early stage of development. Still, findings about cell behavior in a test tube alone are insufficient. Cell tests have to be so well controlled that they really allow conclusions about the situation in a patient. In a certain way this, in turn, is more chaotic, as many different cell types are involved.
Is it possible to make reliable statements with cells such as, for example, with a mechanical tear-resistance test?
Dr. Buxton: To some extent yes. Let’s take, for instance, collagen structures. For the cells these fibers are their home, and they detect the tiniest differences. Certain structures have a function for these cells, others do not, although this is nearly impossible to see “from the outside.” Neither can we calculate it from the chemical, physical and mechanical description of a product, although there are rules. For example, soft materials tend to give rise to neural cell types during cell differentiation, while stiff materials tend to give rise to bone cells, but these hypotheses always require individual tests.
Geistlich Pharma’s cell research: The researchers investigate, for example, which RNA and which proteins are being expressed in different cell types – depending on their surroundings and the biomaterials with which they interact.
Dr. Buxton: To compare which genes are transcribed in mesenchymal stem cells in various situations or on various biomaterials. This, in turn, allows conclusions about how these stem cells further differentiate, and whether they multiply. Such tests permit “objective” statements on whether a product, for instance, promotes the production of bone-forming cells.
Does your research confirm the general wisdom: the more natural the better?
Dr. Buxton: Nature is certainly a good starting point because cells accept natural biomaterials best. Therefore, Geistlich focuses on preparing its biomaterials as “gently” as possible. On the other hand it is nonsensical to only imitate nature without first understanding it. Mankind remained unsuccessful as long as they continued to design, for example, a flying machine just like a bird. Only when they let go of the natural template did “artificial birds” actually take to the sky.
What does this signify for the development of new products?
Dr. Buxton: Our cell research also puts us in a position to fully understand what happens during regeneration and why our materials work so well. We have made some very interesting discoveries in this area, mainly regarding the differentiation of mesenchymal stem cells into osteoblasts. Now we would like to use the discovered mechanisms further, so not just creating new products by trial and error, but by thoroughly understanding interactions at a cellular level.
What can ideally be achieved through such research?
Dr. Buxton: If a good biomaterial contributes to lowering the complication rate by one percent, for a million patients that at least means 10,000 better treatment results.