[Coupled Analysis of Fluid-Structure Interaction of a Micro-Mechanical Valve for Glaucoma Drainage Devices]. / Gekoppelte Analyse der Fluid-Struktur-Interaktion eines mikromechanischen Ventils für Glaukomdrainageimplantate.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. In therapeutically refractory cases, alloplastic glaucoma drainage devices (GDD) are being increasingly used to decrease intraocular pressure. Current devices are mainly limited by fibrotic encapsulation and postoperative hypotension. Preliminary studies have described the development of a glaucoma microstent to control aqueous humour drainage from the anterior chamber into the suprachoroidal space. One focus of these studies was on the design of a micro-mechanical valve placed in the anterior chamber to inhibit postoperative hypotension. The present report describes the coupled analysis of fluid-structure interaction (FSI) as basis for future improvements in the design micro-mechanical valves. MATERIALS AND METHODS: FSI analysis was carried out with ANSYS 14.5 software. Solid and fluid geometry were combined in a model, and the corresponding material properties of silicone (Silastic Rx-50) and water at room temperature were assigned. The meshing of the solid and fluid domains was carried out in accordance with the results of a convergence study with tetrahedron elements. Structural and fluid mechanical boundary conditions completed the model. The FSI analysis takes into account geometric non-linearity and adaptive remeshing to consider changing geometry. RESULTS: A valve opening pressure of 3.26 mmHg was derived from the FSI analysis and correlates well with the results of preliminary experimental fluid mechanical studies. Flow resistance was calculated from non-linear pressure-flow characteristics as 8.5 × 10(-3) mmHg/µl  · min(-1) and 2.7 × 10(-3) mmHg/µl  · min(-1), respectively before and after valve opening pressure is exceeded. FSI analysis indicated leakage flow before valve opening, which is due to the simplified model geometry. CONCLUSIONS: The presented bidirectional coupled FSI analysis is a powerful tool for the development of new designs of micro-mechanical valves for GDD and may help to minimise the time and cost expended on manufacturing and testing prototypes. Further optimisation of the FSI model is expected to ensure further convergence between the simulation and the results of experimental investigations.

Effects of metal ions on fibroblasts and spiral ganglion cells.

Degeneration of spiral ganglion cells (SGC) after deafness and fibrous tissue growth around the electrode carrier after cochlear implantation are two of the major challenges in current cochlear implant research. Metal ions are known to possess antimicrobial and antiproliferative potential. The use of metal ions could therefore provide a way to reduce tissue growth around the electrode array after cochlear implantation. Here, we report on in vitro experiments with different concentrations of metal salts with antiproliferative and toxic effects on fibroblasts, PC-12 cells, and freshly isolated spiral ganglion cells, the target cells for electrical stimulation by a cochlear implant. Standard cell lines (NIH/3T3 and L-929 fibroblasts and PC-12 cells) and freshly isolated SGC were incubated with concentrations of metal ions between 0.3 µmol/liter and 10 mmol/liter for 48 hr. Cell survival was investigated by neutral red uptake, CellQuantiBlue assay, or counting of stained surviving neurons. Silver ions exhibited distinct thresholds for proliferating and confluent cells. For zinc ions, the effective concentration was lower for fibroblasts than for PC-12 cells. SGC showed comparable thresholds for reduced cell survival not only for silver and zinc ions but also for copper(II) ions, indicating that these ions might be promising for reducing tissue growth on the surface of CI electrode arrays. These effects were also observed when combinations of two of these ions were investigated.

[Concept of a pressure-controlled microstent for glaucoma therapy]. / Konzept eines druckgesteuerten Mikrostents für die Glaukomtherapie.

A pressure-controlled microstent could permanently normalise the intraocular pressure (IOP) for open-angle glaucoma therapy by drainage into the suprachoroidal space. The complex requirements demand new technical solutions as well as an improved understanding of specific cell biological processes at the implant's surface to develop effective local drug delivery (LDD) concepts and surface modifications. Fluid mechanical requirements were derived from physiological data and the analysis of commercial glaucoma implants. The technological basics for the production of suitable structures are refined ultra-short pulse laser technology and 2-photon polymerisation (2PP). All known glaucoma implants induce unwanted cell proliferation resulting in a loss of function. It is assumed that the activity of fibroblasts is low in the suprachoroidal space. However, it was seen that LDD concepts are required to control cell proliferation. Fibroblasts from sclera and choroidea were isolated und cultured as the most relevant cell types for in vitro investigation. Potential materials and drugs were investigated by cell viability tests for biocompatibility or suppression of cell viability. The fluid mechanical analysis leads to smallest stent lumina (ID = 50 µm) at anatomically suitable implant lengths (7 - 10 mm). Only pressure control can manage the individual conditions with changing IOP. Finite element analysis of valves showed the need for highly flexible structures. This can be achieved by combining basic structures with micromechanically active valves added by 2PP. The potential materials show perfect in vitro and in vivo biocompatibility. Ormocers which are best suited for 2PP are also highly biocompatible. The selected drugs paclitaxel and triamcinolon acetonide open a wide therapeutic window to impair fibroblast growth. The surgical procedure was established by implantation of prototypes in rabbit eyes, connecting the anterior chamber with the suprachoroidal space. Highly flexible implants are required for correct placement within the eye. The new concept of the microstent combines biomechanical approaches, technologies for microfabrication and current LDD concepts and opens new perspectives for glaucoma therapy.

A comparison of the mechanical performance characteristics of seven drug-eluting stent systems.

OBJECTIVES: Mechanical properties of drug eluting stents (DES) will be measured to provide comparable numerical data to assess deliverability, and thus clinical performance. BACKGROUND: DES are routinely used in coronary interventions to reduce the rates of restenosis and target vessel revascularizations. Current research is primarily concerned with issues related to late stent thrombosis. However, mechanical properties of DES are a critical determinant of deliverability, and consequently the ultimate arbiter of their clinical performance. METHODS: Mechanical properties (pushability, trackability, crossability) were measured under standardized in-vitro conditions. The vessel models were derived from typical vessel anatomy but adapted to the individual tests. Additionally, profile and bending forces of the stent segment of the delivery system were measured. Seven different commercially available balloon-expandable coronary DES systems were included. All stents were 3.0 mm diameter with a stent length from 14 to 18 mm. RESULTS: The pushability expressed as the ratio of distal force at a specific proximal push force (4N) ranged between 38.66 and 18.53%. The trackability as the mean track-forces ranged from 0.551 N to 1.137 N. One stent system could not pass this test. The mean crossing forces at a 1.4 mm stenosis model ranged from 0.038 N up to 0.103 N. The mean crimped stent profiles ranged from 1.055 mm to 1.198 mm and the bending stiffness of the crimped stent was 17.22 to 47.20 Nmm2. CONCLUSION: Better understanding of mechanical properties of DES shall improve tactile skills of the interventionists during PCI and to improve criteria for DES selection in specific clinical settings.

[Investigation of the mechanisms involved in isolated orbital floor fracture. Simulation using a finite element model of the human skull]. / Untersuchungen zum Entstehungsmechanismus der isolierten Orbitabodenfraktur. Simulation am Finite-Elemente-Modell des menschlichen Schädels.

BACKGROUND: Isolated orbital floor fractures make up a significant proportion of all facial injuries, but the mechanism involved in these injuries to the orbital walls (blow-out fractures) has not yet been completely defined. Two theories have been described, which seem to be mutually exclusive. According to the hydraulic pressure theory, the kinetic energy of the blow is transferred via the incompressible eye tissue to the floor of the orbita, which in turn fractures. The buckling force theory, in contrast, explains these fractures as the result of bending and shear stresses arising from kinetic energy act directly on the orbital rim. MATERIALS AND METHODS: With the aim of elucidating the mechanism of injury, we constructed a simplified finite-element model of the human orbita by 3D optical scanning of a human skull obtained after an autopsy examination. We created a generic approximation model based on empiric data derived from femoral fractures and reported in the literature. Several experiments were conducted to test both the above hypotheses by direct and indirect application of kinetic energy. RESULTS: We simulated different types of shear stress with the finite-element model of the skull. The calculated points of maximum pressure were all within the orbital floor. CONCLUSION: The simulation showed that both mechanisms can lead to fractures, as also documented by recent studies. The generation of a finite-element model and simulation of stresses were initially useful in establishing a method. More detailed studies on the empiric data relating to the various structures and more extensive determination and measurement of different skull and/or orbita geometries are needed before we can achieve a model in which the mechanical attributes of the structures involved are reproduced with closer approximation to the real-life situation.

Biodegradable polymeric stents for vascular application in a porcine carotid artery model: English version.

Over the past years the development of biodegradable polymeric stents has made great progress; nevertheless, essential problems must still be solved. Modifications in design and chemical composition should optimize the quality of biodegradable stents and remove the weaknesses. New biodegradable poly-L-lactide/poly-4-hydroxybutyrate (PLLA/P4HB) stents and permanent 316L stents were implantedendovascularly into both common carotid arteries of 10 domestic pigs. At 4 weeks following implantation, computed tomography (CT) angiography was carried out to identify the distal degree of stenosis. The PLLA/P4HB group showed a considerably lower distal degree of stenosis by additional oral application of atorvastatin (mean 39.81 ± 8.57 %) compared to the untreated PLLA/P4HB group without atorvastatin (mean 52.05 ± 5.80 %). The 316L stents showed no differences in the degree of distal stenosis between the group treated with atorvastatin (mean 44.21 ± 2.34 %) and the untreated group (mean 35.65 ± 3.72 %). Biodegradable PLLA/P4HB stents generally represent a promising approach to resolving the existing problems in the use of permanent stents. Restitutio ad integrum is only achievable if a stent is completely degraded.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Structural alterations of adhesion mediating components in cells cultured on poly-beta-hydroxy butyric acid.

Polymers may serve as a biodegradable material in tissue engineering. To assess the biocompatibility of poly-beta-hydroxy butyric acid (PHB), we studied the structural organization of cellular molecules involved in adhesion using osteoblastic and epithelial cell lines. On PHB, both cell lines revealed a rounded cell shape due to reduced spreading. The filamentous organization of the actin cytoskeleton was impaired. In double immunofluorescence analyses we demostrated that the colocalization of the fibronectin fibrils with the actin filaments was lost in cultures on PHB. Similarly, collagen II distribution was altered, whereas the organization of collagen I was not obviously affected. Further evidence for impaired structural organization was obtained for the beta1-integrin receptor and vinculin which mediate the interaction of the cytoskeleton with the extracellular matrix. In confluent epithelial cells, the tight junction protein ZO-1 showed a larger lateral extension in the cell-cell contacts when cells were grown on PHB. Because structural organization of components which mediate cell-matrix and cell-cell adhesion controls cell physiology these parameters could be a sensitive indicator for the biocompatibility of implant materials.

Laser cutting: influence on morphological and physicochemical properties of polyhydroxybutyrate.

Polyhydroxybutyrate (PHB) is a biocompatible and resorbable implant material. For these reasons, it has been used for the fabrication of temporary stents, bone plates, nails and screws (Peng et al. Biomaterials 1996;17:685). In some cases, the brittle mechanical properties of PHB homopolymer limit its application. A typical plasticizer, triethylcitrate (TEC), was used to overcome such limitations by making the material more pliable. In the past few years, CO2-laser cutting of PHB was used in the manufacturing of small medical devices such as stents. Embrittlement of plasticized PHB tubes has been observed, after laser machining. Consequently, the physicochemical and morphological properties of laser-processed surfaces and cut edges of plasticized polymer samples were examined to determine the extent of changes in polymer properties as a result of laser machining. These studies included determination of the depth of the laser-induced heat affected zone by polariscopy of thin polymer sections. Molecular weight changes and changes in the TEC content as a function of distance from the laser-cut edge were determined. In a preliminary test, the cellular response to the processed material was investigated by cell culture study of L929 mouse fibroblasts on laser-machined surfaces. The heat-affected zone was readily classified into four different regions with a total depth of about 60 to 100 microm (Klamp, Master Thesis, University of Rostock, 1998). These results correspond well with the chemical analysis and molecular weight measurements. Furthermore, it was found that cells grew preferentially on the laser-machined area. These findings have significant implications for the manufacture of medical implants from PHB by laser machining.

Biocompatibility and surface structure of chemically modified immunoisolating alginate-PLL capsules.

Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.

[Characteristic mechanical properties of balloon-expandable peripheral stent systems]. / Mechanische Eigenschaften peripherer ballonexpandierbarer Stentsysteme.

PURPOSE: To measure in vitro geometric-mechanical characteristics of balloon-expandable peripheral stent systems for determining suitability for specific vascular regions. MATERIALS AND METHODS: Balloon-expandable stents including their delivery systems manufactured by Guidant (OTW Megalink trade mark ), Inflow Dynamics (Antares), Medtronic (AVE Bridge trade mark ), Biotronik (Peiron trade mark ) and Cordis (Corinthian IQ trade mark ) were selected for this study. When expanded, all stents had a nominal diameter of 8 mm. The length was 38 - 40 mm. Stent profile, trackability, length change on expansion, stiffness, elastic recoil, and radio-opacity in the crimped and expanded state of these stent systems were determined with specially developed test methods. RESULTS: The Corinthian IQ trade mark, Megalink trade mark and Peiron trade mark required the smallest force to pass through the vascular model. While the Bridge trade mark system had the largest profile with a diameter of 2.430 mm, all other stent systems had a significantly smaller diameter ranging from 1.970 mm for the Peiron trade mark to 2.078 mm for the Corinthian IQ trade mark. In the distal region of the stent delivery system, the Megalink trade mark was the most flexible and the Bridge trade mark system the stiffest. Elastic recoil for all stents was in the range of 2.5 % to 3.5 %, with the exception of the Bridge trade mark stent, which had an elastic recoil of 4.79 %. The Corinthian IQ trade mark stent had noticeably the highest radial stiffness. In the expanded condition, the Peiron trade mark was the most flexible while the Corinthian IQ trade mark and the Antares trade mark were found to be the stiffest. Length change (shrinkage on expansion) ranged from 0.54 to 6.57%, with the exception of the Corinthian IQ, which shrunk > 7mm (18.5%) on expansion. All stent systems in the crimped and expanded state were readily visible radiographically. CONCLUSION: Specific data of significant parameters are available to aid in the selection of balloon expandable stents systems to be deployed in complex vascular regions. All examined stent systems showed adequate mechanical properties, but clinically relevant differences were found in stent trackability, bending stiffness and shrinkage on expansion.

Assessment of explanted PTCA balloons.

The data presented here are part of a on-going study to define the surface characteristics and properties of explanted PTCA catheters in a further effort to address some of the ramifications of the re-use issue. PTCA balloon catheter were examined after angioplasty in one hundred and sixty-eight patients (n = 168). This series included six balloon types from three manufacturers. The fresh fixed and dehydrated balloons were examined at first with light microscopy and then in a scanning electron microscope. X-ray semiquantitative microanalysis and FT-IR-ATR analysis were also performed on the balloons. Because most blood proteins are water soluble, we examined unfixed balloons with a protein silver staining kit for detection of adhered proteins described by Heukeshoven. A further method for protein detection is the Lowry-analysis. With this method water insoluble proteins can be observed. Our study has shown convincingly that all deployed angioplasty catheters were coated with adherent protein layers. Plaque particles were found embedded in the surfaces of most of the balloons examined. Fissuring and micro tearing of balloon surfaces was noted. FT-IR-ATR analyses of the blood contacted balloon surfaces did not show any peaks indicative of proteins on the balloon surface. The silver staining method also did not show any evidence of protein adsorption on the balloons. On the other hand, the Lowry-analysis yielded clear evidence that water insoluble proteins were adherent to the balloon surfaces. The average measured protein concentration was 17 microg/ml.

The loss of stiffness as osteoporosis progresses.

The routine diagnosis of osteoporosis is based on radiological measurements of bone mineral content. An osteoporotic failure is influenced both by a loss of mineralized bone and internal bone structure. The structure cannot be estimated by bone reconstruction based on standard radiological equipment. To investigate the influence of structure on cancellous bone stiffness, a new finite element model of cancellous bone is developed. The model describes a cancellous bone unit as an open-celled structure. Trabecular length, trabecular thickness, diameter of trabecular connections, relative lattice disorder and relative bone loss determine the real architecture. Using this model, the loss of stiffness as a result of trabecular thinning and loss of trabecular connections is estimated. The volume fraction as a scalar value for a volume can not be a marker for orthotropic stiffness changes. A formula in the form Y = e(a *1 n(X) + b) can describe the correlation between cancellous bone stiffness and volume fraction. These formulas are appropriate for those cases, when the loss of bone mineral (decrease in trabecular thickness) is closely connected to a loss of structure (increasingly perforated trabecular network).

Relationship between design and control of artificial heart for protection of the right/left balance.

Right/left matching in the total artificial heart (TAH) is essential to prevent fatal volume displacement into the pulmonary circuit. Measurements were made with three different sized Rostock pneumatic artificial ventricles incorporated in the Donovan mock circulatory system together with the heart driver AKT 86. First for each ventricle we determined the dependence of the maximum effective stroke volume on the systolic driving pressure and the afterload. The right ventricle (RV) is about 10% more effective than the left ventricle (LV). Control of the TAH permits different or equal frequencies for the RV and LV. For control with equal frequencies and full-to-empty regimen of one ventricle (RV-Master or LV-Master) the ratio of designed stroke volumes between RV and LV is important. This follows from the smaller efficiency of the LV and the left-to-left shunt. Otherwise a control mode with different heart rates must be used.

[Biomaterials in urology]. / Biowerkstoffe in der Urologie.

Biomaterials are defined as non-living materials which are used in interaction with biological systems. Especially in the field of urology, biomaterials are applied in urinary diversion, urinary incontinence, erectile dysfunction, and as cosmetic prostheses. Biomaterial-tissue interaction is caused by the physical and chemical characteristics of the biomaterial, its degradation, and the resulting protein denaturation. General requirements include biocompatibility and functionality and the avoidance of carcinogenic, mutagenic, toxic, and allergic reactions. This is most important when there is permanent contact between urine and epithelial tissue, which may lead to biofilminfection and incrustation. Continuous modification of known materials, inauguration of new materials, as well as the possibilities of tissue engineering will determine their development in the years to come.

[Bioartificial materials in urology]. / Bioartifizielle Materialien in der Urologie.

The scope of our research is the development of polymer-based bioabsorbable stents for urologic applications and in vitro testing of tissue reactions of cultured ureteral and urethral segments induced by implanted polymer stent prototypes. For these purposes a tissue cultivation model was developed using selected techniques of tissue engineering. Essential advantages of degradable over nondegradable urethral stents are elimination of the adverse extraction of epithelialized stents and the potential for recovery of organ-specific functionality. Moreover, the biocompatibility of a degradable urethral stent could potentially reduce the risk of restenosis due to hyperplasia and could be used, even repeatedly, for the treatment of a number of subvesical obstructions. For the treatment of tumor-induced strictures, application of degradable polymer stents coated with cytostatic drugs may be possible. The mechanical effect of the drug-loaded stent as a "place holder" could be complemented by adjuvant or palliative approaches such as local chemotherapy. We have developed and tested in vitro a degradable urethral stent incorporated with the model drug methotrexate for local drug delivery (LDD) by diffusion and during stent degradation.

[Polyurethane or silicone as long-term implant substance--a critical evaluation]. / Polyurethan oder Silikon als Langzeitimplantatwerkstoff--eine kritische Wertung.

Long-term implants made from thermoplastic elastomers have a long history of clinical use. Among other rubber materials, such as polyolefin rubber, much of the demand for rubber-like biomaterials is met by silicone and polyurethane elastomers. The last two elastomers both have sufficient biocompatibility for long-term applications, but differ in terms of biodegradability. Inadequate resistance to degradation almost always leads to implant function loss, which may even threaten the patient's life. Long-term implantation studies in the rat show different mechanisms of biodegradation for polyurethane and silicone. Polyurethane shown deep fissures in the surface, compared with erosion of silicone surfaces. Mechanical and electrical parameters determined to evaluate degradation, additionally show differences in the extent of damage occurring.

The impact of material characteristics on the mechanical properties of a poly(L-lactide) coronary stent.

Biodegradable polymer stents as an alternative to metallic vascular stents have long been under discussion. However, for various reasons no such stent concept has been made available for commercial use until today. One reason may be, that still little is known about the mechanical properties of polymer stents and their dependency on the material characteristics. In this study, finite element analysis is used to investigate the mechanical properties of a balloon expandable PLLA stent under various load conditions. It is shown, how material parameters, such as elastic modulus, yield level and material hardening, influence stent recoil and collapse behavior.

[A measuring procedure for experimental determination of tensile strength of catheters and flexible probes]. / Messverfahren zur experimentellen Bestimmung der Biegesteifigkeit von Kathetern und flexiblen Sonden.

In order to obtain a more objective description of the properties usually subsumed under such terms as the "handling" of catheters, it is necessary to measure the significant parameter bending stiffness. A contact-free method of recording the oscillations of rod-shaped elements is presented. The stiffness EI can be calculated from the measured characteristic frequency. The logarithmic decrement can be derived from the damped natural oscillation and the damping properties of the catheter thus characterised. In addition, a consideration of imposed oscillations can be employed to calculate resonance frequency. A computer-driven measuring set-up employing a CCD line camera for the non-contact recording of oscillations of rodshaped elements, together with the software required is presented. The measuring principle and possible errors are discussed and a measurement described by way of an example.

[Comparative analysis of in vitro test procedures for evaluating hemocompatibility of cardiovascular stents]. / Vergleichende Analyse von in vitro Testverfahren zur Beurteilung der Hämokompatibilität von kardiovaskulären Stents.

Within the scope of this study existing in vitro techniques for testing the hemocompatibility of coronary stents were analysed and optimised. Static and quasi-stationary systems were compared to a pulsed flow model with respect to platelet activity. The streamlines were visualized by dye injection. Blood flow was measured by ultrasonic Doppler velocity meter and electromagnetic flow meter. Uncoated stainless steel (316 L) stents were tested. Surrogate parameters of the hemocompatibility were the change in surface morphology after blood contact and the rise of biomechanical activation markers as C3a and beta-thromboglobulin. The results were correlated to the stent design and to the flow characteristics of the test systems.