Magnesium sponges as bioresorbable implants
Project description:
On the basis of previous results, degradable osseous implants will be refined for use in weight-bearing areas. Novel hybrid ceramic magnesium sponge structures will be designed to ensure enhanced resilience and biocompatibility, as well as a suitable, specially tailored rate of degradation. Load magnitudes at the site will be recorded and calculated by simulating optimal structures. Magnesium-cell interactions are to be characterised at both the molecular-biological and histological level in order to identify, and specifically optimise, critical parameters.
The studies to date revealed that, with regard to their use as implant material in bone and in cartilaginous regions, magnesium sponges show both beneficial properties and others that require improvement. The outstanding advantages over other biodegradable materials were confirmed as being their greater strength, their elasticity (which is comparable with that of bone), and the good solubility and biological compatibility of Mg++ ions as a degradation product. Interestingly, it was shown that implants made from magnesium alloys may have an osteoinductive effect in vivo. Sponges consisting of various magnesium alloys were created with a high degree of reproducibility. Special programs were developed in order to mathematically define the mechanical properties of these sponges and to use the data for calculating an optimal structure. Finite-element simulations performed under pressure or tensile loading revealed that the models agree well with scanning electronic microscope analysis of the test specimens produced. In particular, degradation and the causes of failure in the peripheral areas were simulated and determined. The results show that, especially in thin-walled sponges, higher strength is required. The degradation of sponges and solid material without cavities was compared under specific technical conditions, under cell culture conditions and in vivo. Whereas, under specific technical conditions, precise and reproducible findings were routinely achievable, degradation under cell culture conditions and in vivo was very much slower and, to some extent, not homogenous. The degradation rate proved to be dependent on both the composition of the alloys and on the production process. As expected, degradation progressed considerably faster in sponges than in solid specimens, so that, if the envisaged functional duration is to be achieved, it is essential that the degradation rate be significantly reduced. Compared with fresh bone cement, biocompatibility tests in various cell culture models produced a positive picture with regard to the soluble degradation products of the tested alloys. Cells were even able to adhere to slowly degrading test specimens. As in cell culture, slowly degrading implants showed better tissue compatibility; in the rapidly degrading sponges, an osteoinductive effect was not observed. As an aid to understanding the underlying molecular processes, a custom DNA array chip was produced to analyse gene expression. Overall, it emerged that the stability of these sponges must be improved and their degradation slowed. To this end, novel composite materials are to be developed in which bone-compatible ceramic particles or bioglasses will be inserted as a spacer for the magnesium sponges. These spacers are to remain in the sponge after production, thus both improving mechanical strength and reducing the degradation rate. The intention is that, during the degradation of magnesium alloys in bone, the spacer material will initially remain as a porous matrix, which becomes populated by cells and can then gradually become ossified. In order to understand the molecular processes involved, a mouse model will be established which allows both histological evaluation of the implant environment and gene expression analyses by means of DNA arrays.
In order that the findings of gene expression analyses in the mouse can be transferred to the larger animal model, hybridising probes will be used to investigate the gene expression in rabbit tissue that corresponds to that in mouse tissue.
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