There are cascades of events ranging from inflammation and wound healing to bone remodeling after the implantation of foreign material into organisms. Specialised cells such as macrophages, osteoclasts, and osteoblasts are key regulators of these processes. Furthermore, crosstalk between cells via e.g. cytokines, increases the complexity level of this fine regulated network.
Our focus is to elucidate the response of different cells, their specific adjustments and modifications at the interface to metallic biomaterials.
Therefore several constitutive steps are combined
- development of cell culture models for in vitro investigations
- identification of key parameters indicating sensitive cellular processes
- description of cell responses at the interface of cells and biomaterials
Cell culture models
differentiated osteoblasts (small) promote the activity of osteoclasts (large, round) in a coculture © Steven Behr
It is essential to establish and apply cell (co)culture models in vitro in order to reflect an in vivo situation. These models are a prerequisite to understand the complex reaction and interaction with biomaterials. Human primary cells are favored.
The successful establishment of a coculture model includes the optimisation and adaptation of growth conditions according to the preferences of the single cell types, the characterisation of phenotype and molecular markers under undisturbed culture conditions and the control of growth-promoting intercellular signaling.
To understand the effect of the material on the different cell types, adjustments or modifications of specific cell characteristics or cell markers are studied on molecular, biochemical and functional level. For example, osteoblasts are responsible for bone and extracellular matrix formation and mineralisation. Thus, markers representing their ability to produce calcium-rich deposits are monitored via gene and protein expression as well as by colorimetric cell assays.
Cells interacting with biomaterials
mesenchymal stem cells under differentiation on the surface of a magnesium alloy disc © Jorge Gonzales
Utilising these key parameters, cell response is investigated under the influence of metal degradation products or in direct contact with different metal surfaces. Promoting events are of special interest but also disturbances of cell to cell communication pathways as well as growth-inhibiting effects.
We are a chain link
Results from the in vitro tests are fed back to the material development and its processing in order to improve cytotoxic and inhibiting properties of the magnesium-based alloys themselves or of their degradation products. In addition, the effects of different cell types on material degradation (e.g., degradation and microstructural changes) are analysed in collaboration with the department "Material Design and Characterisation". Various strategies, such as porous metallic scaffolds, the modification of alloying elements and coatings with biomolecules are being pursued to increase bone integration and/or osteoinduction. Thanks to inter-department collaboration, structure-function relationships of biomaterials or biomimetic materials (e.g., coatings or material structure) can be explored through X-ray and neutron structure research.
If individual alloys have proven particularly promising in vitro, prototypes of these materials are implanted in vivo. These experiments are done in close cooperation with external partners, and performance and possible side reactions of the implant material are tested.