Microfabricated bioelectrodes on self-expandable NiTi thin film devices for implants and diagnostic instruments.

State of the art minimally invasive treatments and diagnostics of neurological and cardiovascular diseases demand for flexible instruments and implants that enable sensing and stimulation of bioelectric signals. Besides medical applications, implantable bioelectronic brain-computer interfaces are envisioned as the next step in communication and data transfer. Conventional microelectrode arrays used for these types of applications are based on polymer substrates that are not suitable for biostable, rigid and self-expanding devices. Here, we present fully integrated bioelectrodes on superelastic NiTi carriers fabricated by microsystem technology processes. The insulation between the metallic NiTi structure and the Pt electrode layer is realized by different oxide layers (SiOx, TaOx and Yttrium stabilized Zirconia YSZ). Key properties of bioelectronic implants such as dissolution in body fluids, biocompatibility, mechanical properties and bioelectrical sensing/stimulation capabilities have been investigated by in vitro methods. Particular devices with YSZ are biostable and biocompatible, enabling sensing and stimulation. The major advantage of this system is the combination of medically approved materials and novel fabrication technology that enables miniaturization and integration beyond the state-of-the-art processes. The results demonstrate that this functionalization of superelastic NiTi is an enabling technology for the development of new kinds of bioelectronic devices.

Cell adhesion on NiTi thin film sputter-deposited meshes.

Scaffolds for tissue engineering enable the possibility to fabricate and form biomedical implants in vitro, which fulfill special functionality in vivo. In this study, free-standing Nickel­Titanium(NiTi) thin film mesheswere produced by means of magnetron sputter deposition.Meshes contained precisely defined rhombic holes in the size of 440 to 1309 µm2 and a strut width ranging from 5.3 to 9.2 µm. The effective mechanical properties of the microstructured superelastic NiTi thin film were examined by tensile testing. These results will be adapted for the design of the holes in the film. The influence of hole and strut dimensions on the adhesion of sheep autologous cells (CD133+) was studied after 24 h and after seven days of incubation. Optical analysis using fluorescence microscopy and scanning electron microscopy showed that cell adhesion depends on the structural parameters of the mesh. After 7 days in cell culture a large part of the mesh was covered with aligned fibrous material. Cell adhesion is particularly facilitated on meshes with small rhombic holes of 440 µm2 and a strut width of 5.3 µm. Our results demonstrate that free-standing NiTi thin film meshes have a promising potential for applicationsin cardiovascular tissue engineering, particularly for the fabrication of heart valves.

Bioactive compounds immobilized on Ti and TiNbHf: AFM-based investigations of biofunctionalization efficiency and cell adhesion.

Implant materials require optimal biointegration, including strong and stable cell-material interactions from the early stages of implantation. Ti-based alloys with low elastic modulus are attracting a lot of interest for avoiding stress shielding, but their osseointegration potential is still very low. In this study, we report on how cell adhesion is influenced by linear RGD, cyclic RGD, and recombinant fibronectin fragment III8-10 coated on titanium versus a novel low-modulus TiNbHf alloy. The bioactive molecules were either physisorbed or covalently coupled to the substrates and their conformation on the surfaces was investigated with atomic force microscopy (AFM). The influence of the different bioactive coatings on the adhesion of rat mesenchymal stem cells was evaluated using cell culture assays and quantitatively analyzed at the single cell level by AFM-based single-cell force spectroscopy. Our results show that bioactive moieties, particularly fibronectin fragment III8-10, improve cell adhesion on titanium and TiNbHf and that the covalent tethering of such molecules provides the most promising strategy to biofunctionalize these materials. Therefore, the use of recombinant protein fragments is of high importance for improving the osseointegration potential of implant materials.

Cell adhesion strength is controlled by intermolecular spacing of adhesion receptors.

Spatial patterning of biochemical cues on the micro- and nanometer scale controls numerous cellular processes such as spreading, adhesion, migration, and proliferation. Using force microscopy we show that the lateral spacing of individual integrin receptor-ligand bonds determines the strength of cell adhesion. For spacings > or = 90 nm, focal contact formation was inhibited and the detachment forces as well as the stiffness of the cell body were significantly decreased compared to spacings < or = 50 nm. Analyzing cell detachment at the subcellular level revealed that rupture forces of focal contacts increase with loading rate as predicted by a theoretical model for adhesion clusters. Furthermore, we show that the weak link between the intra- and extracellular space is at the intracellular side of a focal contact. Our results show that cells can amplify small differences in adhesive cues to large differences in cell adhesion strength.

[Mucormycosis in paranasal sinuses]. / Mucormykosen der Nasennebenhöhlen.

Three patients with mucormycosis of the paranasal sinuses were treated in the University ENT departments in Bochum and Essen in recent years. All patients were immunocompromised for different reasons and had reduced resistance against microorganism infection. They presented with symptoms of orbital complications of sinusitis. The further progress of these life-threatening fungal infections with a mortality rate between 35 and 70% depends on early and definitive diagnosis and radical surgical therapy to reduce the amount of infectious agent. The difficulties of early diagnosis by imaging, histology, microbiology, or molecular biology and postoperative therapeutic options especially with amphotericin B, liposomal amphotericin B, and posaconazole are illustrated and discussed.

[Patients' satisfaction after nasal septal and turbinate surgery. Results of a questionnaire]. / Ergebnisse einer Umfrage zur Patientenzufriedenheit nach Nasenseptumplastik und Muschelbehandlung.

INTRODUCTION: Regarding the satisfaction of patients efficiency and outcome of surgery on the nasal septum and the turbinates regularly is the topic of controversial discussion and occasionally some health authorities doubt there is an indication for these procedures in general. Subjective and objective evaluation of surgical outcome do not necessarily match in all cases. METHODS: A standardized questionnaire was sent to patients having undergone surgery on the nasal septum and the turbinates 33-45 months ago at a university hospital and a non-university hospital. Topics (10 all together) were e. g.: nasal aeration, sense of smell, rhinorrhea, snoring, general condition. Statistic significance of each parameter was verified. RESULTS: 138 questionnaires were reviewed. 82% of the candidates reported better aeration of the nose after surgery. 71% stated to have benefited from the operation. A relevant positive effect on snoring, rhinorrhea, headache and sense of smell could not be proved. The results did no different whether surgery was performed at a university hospital or at a non-university-hospital. Older patients seem to profit more from the procedure than younger ones. DISCUSSION: The survey clearly shows, that surgery on the nasal septum with turbinoplasty has a positive effect on the nasal aeration and the general condition. Therefore its performance is well justified when after careful verification of the pre-conditions the indication for surgery is given.

[Wegener's granulomatosis and orbital complications of sino-nasal origin]. / Zur sinugenen orbitalen Komplikation bei Morbus Wegener.

Wegener's granulomatosis is an idiopathic, granulomatous disease with the potential for multiple head and neck manifestations (80 % of the patients). Sinonasal symptoms are observed in more than 60 % of the patients. Due to these facts the otorhinolaryngologist plays an essential role in the multidisciplinary team involved in establishing the diagnosis early, initiating immunosuppressive therapy and providing ongoing care. The treatment is based on medical therapy consisting of corticosteroids and immunosuppressive agents, whereas surgery is reserved for selected head and neck manifestations. By means of 3 patients presenting with distinct visual loss in consequence of orbital complications with sinonasal origin the course of disease and theoretical background are reviewed. In our patients Wegener's granulomatosis was diagnosed by histopathological examination and serological detection of ANCA, cANCA. The progression of the granulomatous process and an additional purulent inflammation in 2 cases led to a temporary amaurosis and in another case to a visual loss of 50 %. Immediate orbital decompression in combination with sufficient systemic immunosuppressive treatment relieved the compression of the optical nerve and preserved vision. We conclude that early orbital decompression either by external or endonasal approach and concomitant immunosuppression is necessary to determine or improve rapidly decreasing vision subsequent to high intraorbital pressure produced by a granulomatous process and inflammation.

[Osteosynthesis in facial bones: silicon nitride ceramic as material]. / Osteosynthese im Gesichtsschädelbereich: Siliziumnitritkeramik als Werkstoff.

BACKGROUND: The favorable properties of silicon nitride (Si3N4) ceramic, such as high stability and biocompatibility suggest its biomedical use as an implant material. The aim of this study was to test its suitability for osteosynthesis. MATERIALS AND METHODS: A Si3N4 prototype minifixation system was manufactured and implanted for osteosynthesis of artificial frontal bone defects in three minipigs. After 3 months, histological sections, CT and MRI scans were obtained. Finite element modeling (FEM) was used to simulate stresses and strains on Si3N4 miniplates and screws to calculate survival probabilities. RESULTS: Si3N4 miniplates and screws showed satisfactory intraoperative workability. There was no implant loss, displacement or fracture. Bone healing was complete in all animals and formation of new bone was observed in direct contact to the implants. CONCLUSIONS: Si3N4 ceramic showed a good biocompatibility outcome both in vitro and in vivo. This ceramic may serve as biomaterial for osteosynthesis, e.g. of the midface including reconstruction of the floor of the orbit and the skull base. Advantages compared to titanium are no risk of implantation to bone with mucosal attachment, no need for explantation, no interference with radiological imaging.

[Long-term results of laser-tonsillotomy in obstructive tonsillar hyperplasia]. / Langzeitverlauf nach Laser-Tonsillotomie bei symptomatischer Tonsillenhyperplasie.

BACKGROUND: Carbon-dioxide-laser-tonsillotomy is reconsidered as a procedure to relieve patients in early childhood from obstructive symptoms caused by tonsillar hyperplasia such as snoring or sleep apnea without influencing the immunological function. METHODS AND PATIENTS: The protruding part of the tonsils was removed by a CO (2)-laser delivering 10 - 15 W. During 1993 to 2003, 83 children received laser-tonsillotomy, combined with adenoidectomy 51 children were available for follow-up with a standard questionnaire. The parents were surveyed in average 39 months postoperatively. 5 patients required a subsequent tonsillectomy due to a recurrence of tonsillar hyperplasia. Histological investigations were done. 15 children were reevaluated by clinical examination. RESULTS: Most of the patients were relieved from obstructive symptoms. There was no occurrence of postoperative hemorrhage or peritonsillar abscesses. The histological investigations on the specimens from later performed tonsillectomy (n = 5) showed no evidence of scarring opened crypts. The clinical examination did not reveal any signs of chronic infections. CONCLUSION: The tonsillotomy by carbon-dioxide-laser appears as a suitable and safe technique for the treatment of tonsillar hyperplasia without severe throat infection in early childhood.

Regional expression of phospholamban in the human heart.

BACKGROUND: Several independent lines of evidence indicate that phospholamban (PLB) expression correlates positively with depression of force of contraction and duration of contraction in isolated cardiac preparations of several animal species. Here, we studied whether PLB levels correlate with attenuation of contractility and enhancement of contractile time parameters in different parts of the human heart. METHODS: Force of contraction was measured in isolated electrically driven atrial and ventricular preparations from human hearts. Ca(2+)-uptake by human atrial and ventricular homogenates was assayed at different ionized Ca(2+)-concentrations. Protein expression of PLB and the sarcoplasmic Ca(2+)-ATPase (SERCA) was measured in homogenates by quantitative immunoblotting using specific antibodies. PLB mRNA expression was quantified in human cardiac preparations by Northern blot analysis. RESULTS: The duration of contraction in isolated preparations of human right ventricle (RV) was double that found in right atrial preparations (RA) (620 +/- 25 ms versus 308 +/- 15 ms). In RA, PLB expression was reduced by 44% at the protein level and by 34% at the mRNA level compared to RV. In contrast, the SERCA protein content was increased by 104% in RA compared to RV. Ca(2+)-uptake at low ionized Ca(2+)-concentration, where the inhibiting effect of PLB is maximal, amounted to 1.39 +/- 0.28 nmol Ca2+/mg protein in RA and to 0.62 +/- 0.09 nmol Ca2+/mg protein in RV (n = 6 both). CONCLUSIONS: It is suggested that duration of contraction is shorter in human atrium versus ventricle due to the combined effect of decreased PLB levels (which inhibits SERCA function) and increased SERCA levels. The lower relative ratio of PLB to SERCA leads to less inhibition of SERCA and increased Ca(2+)-uptake which enhances relaxation and contraction in human atrium.