Papers by Author: Helmut Schubert

Abstract: Polymeric, biodegradable microspheres represent a good reliable system to investigate the release of bioactive substances in both in vitro and in vivo applications. Common biomaterials for the synthesis of these microspheres are aliphatic polyesters of the poly(α-hydroxy)acids, especially poly-L-lactides (PLA) and polyglycolides (PGA) or their copolymers poly-D,L-lactide-co-glycolides (PLGA). In our own previous studies we have developed PLGA microspheres with integrated PGE2 as model substance for a wide range of biomedical applications, especially in angiogenesis, fracture healing and cartilage repair. The synthesis is based on a binary solvent in water emulsion approach, where two different solvents are used to dissolve the active agent and the polymer, while being miscible in each other (CHCl3, ethyl acetate). Both, the degradation of the material and the release profiles were investigated using SEM and mass spectrometry coupled with gas- or high performance liquid chromatography. SEM and AFM measurements indicated a porous structure of the microspheres but could not resolve the true three dimensional structure of the microspheres. Therefore, synchrotron radiation-based µCT (SR-µCT) investigations were performed to link the release profile to the structural design of the microspheres. As a result, we were able to cross validate the experimental data from SEM and AFM with SR-µCT, demonstrating both micro-porosity and nano-porosity. The polymer itself appears to consist of 200 nm – 300 nm sized particles.

Abstract: Biomaterials based tissue engineering requires optimization of several parameters. The most important parameters can be attributed to biocompatibility, degradational behaviour, mechanical stability and structural design. In previous studies we have established a porous gelatine based scaffold material, with parallel oriented pore channels. Although, tomographic data has been derived on dried scaffold samples, it remains unclear how the pore channel network interacts under load in a wet environment. We developed an experimental setup to compress biomaterials in a wet environment during exposure to synchrotron generated X-rays using a micrometer screw with a force sensor. Achieving good X-ray absorption contrast in polymeric biomaterials immersed in water is rather difficult, as water absorption prevents detailed imaging. Phase contrast imaging on the other hand allows for improved imaging results due to the attenuation of phase boundaries in the imaged data, neglecting effects of X-ray absorption in the watery phase nearly completely. Best results were obtained for X-ray energies of 30 keV with a scintillator to sample distance of 1090 mm with the established experimental setup. Due to over attenuation of phase boundaries at higher beam energies, this energy was finally chosen. As a result, we could evaluate the collapsing pore network upon loading with the possibility to enhance the structural design for future studies.

Abstract: Restoring peripheral nerve trauma is an important research field in regenerative medicine. One therapeutical approach is to use tissue engineered nerve conduits consisting of biodegradable polymers. These materials can be designed to include active agents to further stimulate or influence proliferation, maturation, differentiation or migration of specific neuronal cell in these nerve guides. We have developed a method to electrically deposit and immobilize neuronal cells and extracellular matrix proteins on self structured micro electrodes. These electrodes also present a feasible methodology to investigate electrical stimulation of nerve cells. In our approach, poly-D,L-lactide-co-glycolides (PLGA) were investigated as possible substrate for these electrodes, while further allowing for the integration of model substances in a drug release concept. In a first approach, caffeine was used due to its well known effect of both stimulating and inhibiting effects on certain neuronal cells, while also allowing easy incorporation into PLGA via chemical means. A Plackett-Burman experimental design was used to find the optimum composition among different parameters such as drug concentration, polymer concentration, type of solvent and film-drying condition. The optimized drug loaded polymer films were tested for their release and degradation profile, and their behavior in cell culture. Finally, we are currently establishing an integrated experimental setup, combining caffeine modified PLGA film substrates with the manufacturing of the electrode structures to investigate cell deposition via electrical means and stimulation/ inhibition via chemical release.

Abstract: Si3N4 based ceramics that made by hot isostatic press, were implanted at room temperature with N+ - and C+ - ions with energy of 500 keV and 2 MeV, respectively. The specimens were irradiated at a fluence of 1017 ion/cm2. The microstructure changes after ionimplantation in the surface layer were investigated by transmission electron microscopy (TEM). The effect of ion-implantation on the tribological properties was also studied. After N+ and C+ ionimplantation an amorphous layer near to the surface has been formed which was observed by electron diffraction measurement. The wear tests were performed by means of a ball-on-disk configuration using commercially available Si3N4 ball. The friction coefficient was measured online, the wear coefficient was determined on the base of the wear scar sizes. The specific wear rate was reduced by N+-implantation and the coefficient of friction was lower in the initial stage in both cases.