Functionalising implant surfaces
Project description:
The chief aim is the improved, permanent anchoring of endoprostheses. This will be achieved by the development of ultra-thin, functional polymer coatings that act as a contact interface between bone and implant. The intention is that, by providing the coatings with growth factors (rhBMP-2, VEGF-A, Ang-1) and anti-inflammatory factors (IL-1RA, TNF-R), the dynamic process of bone remodelling at the bone-implant interface will be facilitated and that ultimately, even in problematic situations involving replacement of the prosthesis, long-term stability will be achieved.
Endoprosthetic joint replacement in cases of advanced degenerative disorders of the joints is viewed as a milestone in medical history. However, especially in young patients and in situations involving substitution of an existing prosthesis, limited durability and early loosening remain problematic. Improvements in the anchoring of endoprostheses, and especially those lacking long-shafted contact surfaces, will be achieved by optimising the growth of bone onto the prosthesis. Here, minimising the gap between the bone and the prosthetic surface can be regarded as the aim with regard to the development of optimal prostheses. It is hypothesised in this project that minimising the gap between bone and implant surface can be ensured by functionally combining growth factors and anti-inflammatory proteins on the surface of implants.
In the first project period (2003-2006), polymers were developed that serve an anchoring function and thus allow binding of such growth factors (in this case, BMPs), making these substances that are present on the prosthetic surface permanently available to the surrounding cell milieu. The controlled production of recombinant BMP-2 took place concurrently. As, hitherto, biological activity was known only for unbound BMPs in a concentration gradient, we also demonstrated the biological activity of bound peptide in cell cultures and in animal experiments. A coating was created from the polymers and the recombinant BMP-2 that had been produced; this was applied to titanium implants and here constitutes a functional surface on a nanometric scale. This was tested on the femur (using a rabbit model) and integration processes at the bone-implant interface were quantified using micro-CT analyses. This revealed a significant increase in the number of contact points for certain polymer-BMP coatings, demonstrating improved integration of the implant. At the same time, the intracellular signal pathways following binding of BMP-2 to the cell receptor were investigated, especially given that inflammatory cytokines may occur, since wear and foreign-body reactions cause inflammatory responses where endoprostheses are used. An important mechanism contributing to the interference of BMP-2-induced intracellular signal transduction was identified (TAK-1). Inhibition of these mediators communicated via inflammatory pathways may allow unhindered BMP-2 function with stimulation and differentiation of stem cells leading to bone formation, possibly also in situations with accompanying inflammatory reactions.
In the second project period (2007-2010), the focus will increasingly shift to the production, for further in vivo studies, of implants that are coated and biologised with growth factors such as BMP-2. Taking the findings from the initial period as a starting point, work will continue on optimising surface functionalisation with a view to further reinforcing the effect of binding. Other reactive groups will be tested here, with new implant materials such as ceramics and cobalt-chrome also incorporated. Another focus will be on the production of anti-inflammatory factors, including BMPs and angionic factors (rhBMP-2, VEGF-A, Ang-1, IL-1RA, TNF-R). A more differentiated approach to the testing of existing and new surfaces will be adopted; this will involve models – investigating stress, gaps and loosening - that more closely reflect the realities of medical use.
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