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Background The technique of flap-prefabrication has been successfully established in tissue engineering: missing intrinsic vascularisation of engineered tissue can be generated in vivo by microsurgical vesselloop construction. It is possible to move engineered tissue into a defect with microsurgery. In the literature, the combination of engineered tissue covered with skin is not widely reported. Objective Aim of this study was to establish a model to investigate scaffold prefabrication with full thickness skin graft coverage with subsequent free tissue transfer. Methods 8 Wistar rats were operated in 2 separate steps: 1) after creating an arteriovenous loop with the femoral vessels, a porous scaffold was placed on the loop and covered with an inguinally based skin flap. A control was implanted without loop into the contralateral groin. 2) 6 weeks later the prefabricated composite flaps were microsurgically transferred to the cervical region. Skin-island monitoring was performed with Laser Doppler-scanner after the transfer. Results Continuous loss of the skin islands was observed within 72 hours. Complications included wound-dehiscence, thrombosis and death from anaesthesia; in spite of consistent loop viability. Conclusion Evaluation showed that modifications are necessary to maintain the skin-island cove.

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The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed.

The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (M-n=1kDa or 10kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models.

Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0–30 mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10–30% of the cells incorporated particles with ⩾20 mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ⩾20 mol.%. Importantly, the secretion of functional biological mediators by HUVECs was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized Rhodamin B loaded particles with low NVP content may be explored for cell labeling and tracking.

Linear, side-chain methylated oligoglycerols (OGMe) were recently reported as potential surface passivating molecules for improving the protein resistance of cardiovascular application relevant poly(ether imide) (PEI) membranes. A previously reported in vitro screening under static test conditions allowed an end-point evaluation of the adhesion and activation of adherent thrombocytes performed on the material surfaces and revealed similar levels of thrombogenicity on PEI membranes, functionalized with OGMe and oligo(ethylene glycol) (OEG) of similar molecular weight (Mn = 1,300 g·mol−1 - 1,800 g·mol−1). In the present study, we investigated the hemocompatibility of these materials in a dynamic closed loop system, in order to study time-dependent thrombocyte material interactions also of the circulating thrombocytes by mimicking in vivo relevant flow conditions in a dynamic test system with multiple material contacts. Activation and aggregation of circulating thrombocytes as well as complement activation and plasmatic coagulation were evaluated after 40 circulations of thrombocyte rich plasma in the closed loop system. The results of the dynamic tests revealed no differences between the OGMe and OEG functionalized PEI membranes. Furthermore, no differences were observed between the latter and a PEI membrane treated under the conditions of functionalization at pH 11 (PEI-pH11) without an oligoether being present. Blood plasma protein adsorption, as well as activation, and adherence of circulating thrombocytes occurred in a comparable, but minor manner on all investigated PEI membranes. From this we conclude that the OGMe and OEG surface functionalization did not lead to an improvement of the already good hemocompatibility of the PEI-pH11 membrane.

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

Polymers exhibiting cell-selective effects represent an extensive research field with high relevance for biomedical applications e.g. in the cardiovascular field supporting re-endothelialization while suppressing smooth muscle cell overgrowth. Such an endothelial cell-selective effect could be recently demonstrated for a copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and poly(epsilon-caprolactone) segments, which selectively enhanced the adhesion of human umbilical vein endothelial cells (HUVEC) while suppressing the attachment of smooth muscle cells (SMC). In this study we investigated the influence of the fibre orientation (random and aligned) and fibre diameter (2 mu m and 500 nm) of electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC and SMC. Adhesion, viability and proliferation of HUVEC was diminished when the fibre diameter was reduced to a submicron scale, while the orientation of the microfibres did only slightly influence the cellular behaviour. In contrast, a submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds with micron-sized single fibres could be promising candidate materials for cell-selective stent coatings.

Back scattered Laser Doppler (LD) signals are composed of two different individual signals. The number of the moving particles and the speed of the particles in the measured tissue volume determine the frequency shift and the band width of the Doppler signal. The dependence of the Laser Doppler flux on the number of scattering particles is highly nonlinear: at very low hematocrit and high speed the axial migration of the cells to the centre of the blood vessels is very strong, so that in these cases - because of the parabolic flow profile - the Doppler flux measurement overestimates the mean real blood flow (up to two- or three-fold). The opposite is the case when the hematocrit is very high, then the blood flow might be underestimated (due to the increased amounts of blood cells near the vessel wall). In addition, a very change in number of moving particles - as can occur during the postprandial phase or during therapy - can change the signal also at a constant cell number. Also, it must be mentioned that the LD signal possibly is not only reflected by moving blood cells in the different skin layers but also by blood cells flowing in tissues below the skin (particularly below atrophied skin areas of older patients) so that in such cases the LD Flux signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest may still be within the normal range even in advanced states of disease, since the scattered light is sampled from a tissue volume which may contain also non-nutritive shunt vessels. This critical analysis of the LD signals of course shall not lead to an overall rejection of the application of laser Doppler systems. Actual progress only can, however, be obtained under the exact consideration of anatomical conditions, technical restrictions and when generalizations are avoided.

The formation of a functionally-confluent and shear-resistant endothelial cell (EC) monolayer on cardiovascular implants is a promising strategy to prevent thrombogenic processes after implantation. On the basis of existing studies with arterial endothelial cells adhering after two hours on gelatin-based hydrogels in marked higher numbers compared to tissue culture plates, we hypothesized that also venous endothelial cells (HUVEC) should be able to adhere and form an endothelial monolayer on these hydrogels after days. Furthermore, variation of the hydrogel composition, which slightly influences the materials elasticity and even more the degradation behaviour, should have no considerable effect on HUVEC. Therefore, the monolayer formation and shear resistance of HUVEC were explored on two gelatin-based hydrogels differing in their elasticity (Young's moduli between 35 and 55 kPa) in comparison to a positive control (HUVEC on glass cover slips) and a negative control (HUVEC on glass cover slips activated with interleukin-1β) after 9 days of culturing. HUVEC density after 9 days of culturing under static conditions was lower on the hydrogels compared to both controls (p

Common strategies for biofunctionalization of surfaces comprise the immobilization of bioactive molecules used as cell-binding ligands for cell recruitment. Besides covalent binding, multivalent noncovalent physical forces between substrate and ligand are an alternative way to equip surfaces with biomacromolecules. In this study, polymer binding ligands are screened by means of a DNA-based in vitro selection process. As candidate biomaterials poly(ether imide) (PEI), polystyrene, and poly[ethylene-co-(vinyl acetate)] are selected, due to their different chemical structure, but similar macroscopic interface properties, allowing physical interaction with nucleotide bases by varying valences. Multivalent interacting aptamers are successfully enriched by SELEX method and an area-wide surface functionalization is achieved, which can be used for further binding of bioactive molecules. In vitro selection against the polymers result in thymine-dominated aptamer binding motifs. The preferential interaction with thymine is attributed to its chemical structure, connected with a decreased electrostatic repulsion of the π-system and the hydrophobic character maximizing entropy. The aptamer binding stability correlates with available valences for interaction, resulting in a more stable functionalization of PEI.

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.

Endothelial cell (EC) models have evolved as important tools in biomaterial research due to ubiquitously occurring interactions between implanted materials and the endothelium. However, screening the available literature has revealed a gap between material scientists and physiologists in terms of their understanding of these biomaterial–endothelium interactions and their relative importance. Consequently, EC models are often applied in nonphysiological experimental setups, or too extensive conclusions are drawn from their results. The question arises whether this might be one reason why, among the many potential biomaterials, only a few have found their way into the clinic. In this review, we provide an overview of established EC models and possible selection criteria to enable researchers to determine the most reliable and relevant EC model to use.

There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically. This need remains unmet by the biomaterials research community. Recognized stagnation of the blood-biomaterial interface research translates into waning interest from clinicians, funding agencies, and practitioners of adjacent fields. The purpose of this contribution is to stir things up. It follows the 2014 BloodSurf meeting (74th International IUVSTA Workshop on Blood-Biomaterial Interactions), offers reflections on the situation in the field, and a three-pronged strategy integrating different perspectives on the biological mechanisms underlying blood-biomaterial interactions. The success of this strategy depends on reengaging clinicians and on the renewed cooperation of the funding agencies to support long-term efforts.

The endothelialization of cardiovascular prostheses is known to improve their haemocompatibility. As such body-foreign materials often do not endothelialize spontaneously. A lot of in vitro studies are ongoing how endothelialization of biomaterials can be improved. In this study the influence of different components of a tissue-typical extracellular matrix (ECM) like laminin, fibronectin or gelatin on the formation of an endothelial cell monolayer and on the shear resistance of adherent cells on these substrates was studied.The study revealed that the density of human venous endothelial cells (HUVEC) monolayers differed markedly between cells grown on a natural ECM and cells grown on singularized components of an ECM (p < 0.001). Only HUVEC grown on laminin showed similar densities and a stress fiber pattern comparable to HUVEC grown on the ECM. HUVEC grown on gelatin- or fibronectin-coated coverslips were less firmly attached to the substrate; frequently individual HUVEC and even groups of cells detached.Concluding it seems that coating of implants with laminin supports the formation of shear resistant endothelial cell (EC) monolayer - superior to other ECM components.

BACKGROUND: Thrombogenicity is one of the main parameters tested in vitro to evaluate the hemocompatibility of artificial surfaces. While the influence of the temperature on platelet aggregation has been addressed by several studies, the temperature influence on the adherence of platelets to body foreign surfaces as an important aspect of biomedical device handling has not yet been explored. Therefore, we analyzed the influence of two typically applied incubation-temperatures (22 degrees C and 37 degrees C) on the adhesion of platelets to biomaterials. MATERIAL AND METHODS: Thrombogenicity of three different polymers - medical grade poly(dimethyl siloxane) (PDMS), polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) - were studied in an in vitro static test. Platelet adhesion was studied with stringently characterized blood from apparently healthy subjects. Collection of whole blood and preparation of platelet rich plasma (PRP) was carried out at room temperature (22 degrees C). PRP was incubated with the polymers either at 22 degrees C or 37 degrees C. Surface adherent platelets were fixed, fluorescently labelled and assessed by an image-based approach. RESULTS AND DISCUSSION: Differences in the density of adherent platelets after incubation at 22 degrees C and 37 degrees C occurred on PDMS and PET. Similar levels of adherent platelets were observed on the very thrombogenic PTFE. The covered surface areas per single platelet were analyzed to measure the state of platelet activation and revealed no differences between the two incubation temperatures for any of the analyzed polymers. Irrespective of the observed differences between the low and medium thrombogenic PDMS and PET and the higher variability at 22 degrees C, the thrombogenicity of the three investigated polymers was evaluated being comparable at both incubation temperatures.

Within the hemocompatibility testing portfolio of medical devices a range of dynamic models were established in recent years. In contrast to the static hemocompatibility testing method the dynamic models allow considering the impact of hemorheological and hemodynamic blood characteristics on the hemocompatibility of medical devices. Unfortunately the EN DIN ISO 10993-4 for the biological evaluation of medical devices for interaction with blood gives no hints towards the period of time during which the medical devices should be exposed to the blood in these tests. To examine whether different exposure times impact the comparability of hemocompatibility test results low density polyethylene (LD-PE) tubes and nitinol stents were tested exemplarily in a closed loop model for changes of the fibrinogen content, the prothrombin time, the thrombin time, and the C5a activity after 30 and 90 min exposure to the blood. Low density polyethylene was used as negative control because it is one of the European reference materials for hemocompatibility testing. After 90 min blood exposure to the LD-PE tubing and the nitinol stents the prothrombin time was significantly longer and the fibrinogen content significantly lower (p < 0.05) than after 30 min. In contrast the thrombin time and the C5a were comparable after 30 and 90 min blood exposure time. These results might recommend to an initial 30 min exposure time, which is followed by a 90 min exposure time in cases of unclear results.

Trans-catheter pulmonary valve implantation (TPVI) has become the treatment of choice in most congenital heart disease patients with degeneration of a previous right ventricular outflow tract (RVOT) repair. Since the life expectancy of this patient cohort is improving, there is an increased demand of these procedures. Efficacy and safety have been demonstrated for the Medtronic Melody and the Edwards Sapien valves, although there is still a paucity of data and no consistent procedural recommendations are available.

Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of the used blood cells or whole blood, which are not standardized. Here, we report about an in vitro dynamic test system for studying the hemocompatibility of polymeric microparticles utilizing fresh human whole blood from apparently healthy subjects, collected and processed under standardized conditions. Spherical poly(ether imide) microparticles with an average diameter of 140±30 μm were utilized as model systems. Reported as candidate materials for the removal of uremic toxins, these microparticles are anticipated to facilitate optimal flow conditions in a dialyzer with minimal backflow and blood cell damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized microparticles exhibited similarly nanoporous surfaces (PEI: ØExternal pore = 90±60 nm; PEI-KOH ØExternal pore = 150±130 nm) but varying water wettabilities (PEI: θadv = 112±10° PEI-KOH θadv = 60±2°). The nanoporosity of the microparticle surfaces allows the exchange of toxic solutes from blood towards the interconnective pores in the particle core, while an immigration of the substantially larger blood cells is inhibited. Sterilized PEI microparticles were incorporated –air-free –in a syringe-based test system and exposed to whole blood for 60 minutes under gentle agitation. Thereafter, thrombi formation on the particles surfaces were analyzed microscopically. In the collected whole blood the non-adherent/circulating single blood cells were quantified via a differentiated complete blood cell count and the activation of platelets (P-Selectin expression, secretion and release), platelet function (PFA100 closure time) as well as thrombin formation (thrombin-antithrombin-complex) was analyzed. Free hemoglobin (HGB) levels were quantified as a measure of hemolysis. Microscopic evaluation revealed thrombi formation and particle aggregates for all tested microparticles. Reduction of circulating blood cells differed significantly between the particle types. Particularly, platelet and monocyte counts decreased up to 50% compared to the control (syringe filled with whole blood but without microparticles). In accordance, platelet activation, thrombin levels and degrees of hemolysis were clearly elevated in the particle loaded test systems and allowed a differentiation between the particle types. Increased PFA100 closure times (as activating agent a combination of collagen/ADP was used) indicated a similarly reduced ability of platelets to adhere and form stable aggregates independent from the particle type tested. This observation is most probably a consequence of the strong thrombus formation in the test system, which is associated with a reduction of the circulating blood cells. The reported in vitro dynamic whole blood test system allowed the sensitive analysis of the hemocompatibility of polymer-based microparticles and was successfully validated for porous PEI microparticles with different water wettabilities. Beyond the qualitative and quantitative analysis of cell-material interactions, the test also allowed the functional evaluation of platelets in whole blood.

In view of the rare presence of studies concerning platelet function as risk factor in atherosclerotic patients, processes underlying thromboembolic events are reviewed in this paper. The morphology and the structural organization-membrane receptors, the open canalicular and dense tubular systems, the cytoskeleton, mitochondria, granules, lysosomes, and peroxisomes-of platelets are described. Platelet function under physiological conditions in atherosclerosis and after implantation of cardiovascular devices is summarized.

Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers.

Die Magnetokardiographie (MKG) ist eine beruhrungs- und strahlungsfreie, nichtinvasive Methode zur Erfassung der elektromagnetischen Aktivitat des Herzens. Theoretische Gesichtspunkte und vergleichende Untersuchungen deuten auf einen unterschiedlichen Informationsgehalt von MKG und Elektrokardiogramm (EKG) hin. Obwohl eine Vielzahl von Fragestellungen der kardialen Elektrophysiologie und Pathophysiologie durch magnetokardiographische Untersuchungen beantwortet werden kann, ist die Methode immer noch weitgehend unbekannt. Im Vergleich zum EKG ist der Betrieb eines Magnetokardiographen durch Verwendung supraleitender Sensoren mit der Notwendigkeit zur Kuhlung mit flussigem Helium und aufwendiger magnetischer Abschirmung um ein Vielfaches teurer und nicht am Patientenbett verfugbar. Der Gewinn an diagnostischer Information lasst den Aufwand jedoch als gerechtfertigt erscheinen, da die Sensitivitat fur ischamisches Myokard sowohl in Ruhe als auch unter Belastung deutlich hoher ist als die des EKG. Im Hinblick auf die Risikostratifizierung fur den plotzlichen Herztod erlaubt die Magnetfeldanalyse moglicherweise eine genauere Indikationsstellung fur die prophylaktische Defibrillatorimplantation. Die raumliche Auflosung ist hoch genug fur eine nichtinvasive Lokalisation arrhythmogener Foki, was die Methode insbesondere fur das Management von Vorhofflimmerablationen interessant macht. Prospektive und ausreichende klinische Daten fehlen jedoch bisher weitgehend. Es gibt ausreichend Raum fur Fantasien uber weitere Fragestellungen der klinischen Kardiologie, die mit der MKG beantwortet werden konnen.

The cell population of peripheral blood monocytes/macrophages (MO) is heterogeneous: The majority of the MO are CD14++ CD16- and named "classical" (= MO1). Furthermore, two other subpopulations were described: CD14++ CD16+ ("intermediate" = MO2) and CD14+ CD16++ ("non-classical" = MO3). It is reported that MO2 possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic neutrally charged acrylamide-based hydrogel human intermediate (CD14++ CD16+ ), angiogenically stimulated CD163++ monocytes/macrophages (aMO2) maintained a proangiogenic and noninflammatory status for at least 14 days. Here, we explored whether this aMO2 subset adhered to hydrophobic poly(n-butyl acrylate) networks (cPnBA) and also remained in its proangiogenic and noninflammatory status. Because substrate elasticity can impact adherence, morphology, and function of cells, cPnBAs with different Young's modulus (250 and 1100 kPa) were investigated, whereby their elasticity was tailored by variation of the cross-linker content and matched to the elasticity of human arteries. The cPnBAs exhibited similar surface properties (e.g., surface roughness), which were maintained after ethylene oxide sterilization and exposure in serum-free cell culture medium for 18 h at 37°C. aMO2 were seeded on cPnBA samples (1.7 × 10(5) cells/1.33 cm(2) ) in Dulbecco's modified Eagle medium (DMEM high glucose) supplemented with vascular endothelial growth factor 165 (VEGF-A(165) , 10 ng/mL) and fetal calf serum (10 vol%) for 3 and 72 h. On both polymeric samples (n = 3 each), the numbers of adherent cells per unit area were significantly higher (P

Echinocyte formation is associated with a rigidification of the cells that may affect capillary perfusion and, consequently, the tissue oxygen supply. This study examines how many echinocytes appeared after the addition of radiographic contrast media (RCM) (Iodixanol320, Ioversol300, Iopamidol300, and Iomeprol400) compared to red blood cells in autologous plasma and in isotonic saline solution. Isotonic saline solution, Iodixanol, Ioversol, Iopamidol and Iomeprol in concentrations of 10 vol%, 20 vol%, and 40 vol% were added to the plasma of seven healthy subjects. Subsequently, the erythrocytes were resuspended in these plasma/RCM mixtures, incubated for 5 minutes and then examined under the microscope. The concentrations and the RCM in the mixture had a significant effect on the number of discocytes (factor concentration: p < 0.0001; factor RCM: p < 0.0001). The percentage of discocytes for all concentrations depended significantly on the RCM/plasma mixture (concentration × RCM: p < 0.002). Of all RCM/plasma mixtures used, the Iodixanol/plasma mixture showed the most similar discocyte fraction compared to red blood cells in the autologous plasma. Importantly, while Iodixanol differed from all other RCMs, the other RCMs did not differ from one another with respect to the discocyte fraction.

Heart failure patients are clinically characterized by extreme cardiomegaly, breathlessness, fluid retention and an early onset of fatigue. Studies have shown generalized restricted blood flow in those patients. Furthermore animal experiments proved an impaired blood flow and a diminished oxygen supply of the skeletal muscle in animals with chronic heart failure. Patients with chronic heart failure are limited to the extent of their ability to regulate their arterial pressure, especially in physical activity. It is however unclear in what way restriction of blood flow in the main arteries correlates with those in capillaries and to what extent. In this study it was examined the depth of capillary circulatory restriction as well as the disregulation of oxygen partial pressure in skeletal muscle in rest and stress conditions, in patients with terminal heart failure.

As shown in several studies, various properties of biomaterials such as stiffness, surface roughness, chemical composition or the amount of functional groups at the surface can influence adhesion, viability, proliferation and functionalities of cells. The aim of this work was to explore whether a cell-selective effect could be achieved for acrylonitrile-based copolymers containing different contents of positively charged functional groups, which were introduced by incorporation of methacrylic acid-2-aminoethylester hydrochloride (AEMA) units. The p(AN-co-AEMA) copolymers were synthesized by suspension polymerization in water and processed into disk shaped test specimen via a sintering process to ensure the absence of organic solvents in the copolymers. Copolymers with an AEMA content of 1.4, 1.6, and 4.4 mol-% were investigated according to their cell-selective capacity, which should support the adhesion, viability and proliferation of keratinocytes, while the adherence of fibroblasts should rather be disabled. The test samples were seeded with primary human keratinocytes and primary human dermal fibroblasts in mono- as well as in co-cultures. Tissue culture plate polystyrene (TCP) was used to control the physiologic growth of the cells. Density and viability of attached and non-adherent cells were analyzed by live/dead staining, lactate dehydrogenase (LDH) assay and flow cytometry with DAPI staining. For the assured discrimination of adherent cell types in coculture a keratin/vimentin-staining was performed. On copolymers with 4.4 mol-% AEMA adherent keratinocytes in monoculture and cocultured keratinocytes and fibroblasts showed a higher viability, a lower impairment of cell membranes and higher densities of viable cells compared to both other copolymers. For adherent fibroblasts these parameters did not differ between the copolymers and an increasing ratio of keratinocytes to fibroblasts in cocultures were found with increasing AEMA content. The results showed that keratinocytes and fibroblasts can be influenced by copolymers with different contents of positively charged functional groups. Since the tendency of a better adherence and viability of keratinocytes with increasing amounts of positively charged functional groups was shown, the potential enhancement by further increase of the amount of positively charged functional groups shall be tested in a future study.

During extracorporeal circulation (ECC) controlled hypothermia is a common method of myocardial protection due to a reduction of the myocardial oxygen consumption. Although the beneficial aspects of hypothermia on the myocardial metabolism have been widely demonstrated the effect of hypothermia on the myocardial oxygen tension (PmyO2) is unclear. For this reason the PmyO2 of German Landrace pigs (male, three months of age) during ECC was analysed under mild hypothermia (32°C, n = 6 pigs) and under normothermia (n = 10 pigs, control group) within a time period of 23 min (1400 sec). Flexible invasive Clark type microcatheters were used to measure the PmyO2 in the beating heart. During normothermal ECC a continuous PmyO2 increase from 36.5 ± 15.8 mmHg to 52.6 ± 27.2 mmHg (+44.1%) after 1400 sec was measured (p = 0.02). In contrast, mild hypothermia caused a continuous PmyO2 decrease from initially 46.9 ± 17.5 mmHg to 36.7 ± 20.8 mmHg (−21.8%, p < 0.013) in the test period. Electrocardiography revealed no signs of ischemia or arrhythmia during normo- and hypothermic ECC. It seems obvious that mild hypothermia results in a reduction of the oxygen transfer to the myocardial cells and that this effect outweighs the beneficial effects of hypothermia in the myocardium which are related to reduced oxygen consumption. However, in mild hypothermia oxygen supply to the myocardium remained sufficient for normal myocardial function.

The chemical composition of a substrate can influence the adhesion, viability and proliferation of cells seeded on the substrate. The aim of this work was to investigate the influence of different cationic or anionic moieties in acrylonitrile-based copolymers on the interaction with fibroblasts. A series of ten different types of acrylonitrile-based copolymers with a random sequence structure was prepared using a water born synthesis process to exclude potential residues of organic solvents. As charged comonomers cationic methacrylic acid-2-aminoethylester hydrochloride (AEMA), N-3-amino-propyl-methacrylamide hydrochloride (APMA) and anionic 2-methyl-2-propene-1-sulfonic acid sodium salt (NaMAS) were utilized. By application of a specific sintering procedure the copolymer materials were processed into transparent disks for conducting cell tests in direct contact. The copolymers were analyzed with respect to their composition and surface properties. Cytotoxicity tests of the polymer extracts, as well as of the disks were performed with L929 mouse fibroblasts. All copolymers showed no cytotoxic effects. Furthermore, for higher molar ratios of AEMA an increase in cell growth could be observed, which might be a hint that higher charge densities are favorable for the proliferation of L929 cells.

A major clinical problem of high relevance in the cardiovascular field is late stent thrombosis after implantation of drug eluting stents (DES). Clinical widely used DES currently utilize durable polymer coatings, which can induce persistent arterial wall inflammation and delayed vascular healing resulting in an impaired endothelialization. In this study we explored the interaction of smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC) with electrospun scaffolds prepared from resorbable polyetheresterurethane (PDC) and poly(p-dioxanone) (PPDO), as well as polyetherimide (PEI), which can be surface modified, in comparison to poly(vinylidene fluoride-co-hexafluoropropene) (PVDF) as reference material, which is established as coating material of DES in clinical applications. Our results show that adhesion could be improved for HUVEC on PDC, PPDO and PEI compared to PVDF, whereas almost no SMC attached to the scaffolds indicating a cell-specific response of HUVEC towards the different fibrous structures. Proliferation and apoptosis results revealed that PPDO and PEI have no significant negative influence on vitality and cell cycle behaviour compared to PVDF. Hence, they represent promising candidates for temporary blood vessel support that induce HUVEC attachment and prevent SMC proliferation.

Soft hydrophobic poly(n-butyl acrylate) networks (cPnBA) were developed as entropy elastic substrates for passive mechanical stimulation of cells, where the elastic modulus of the cPnBAs could be systematically adjusted by variation of the cross-link density. The networks were synthesized by thermally-induced radical polymerization from n-butyl acrylate, with poly(propylene glycol) dimethacrylate (PPGDMA) acting as cross-linker, whereby the purity of the cPnBAs was confirmed by(1) H-NMR spectroscopy and gas chromatography. In this work two cPnBA polymer networks with an elastic modulus around 200 kPa and 1 MPa were investigated having an elastic modulus similar to that of arteries. Both cPnBAs exhibited an almost smooth surface with a surface roughness (R q) in the wet state ranging from 17 to 37 nm and a similar zetapotential, indicating an almost identical chemical composition within the topmost surface layer in terms of functional groups. In contrast, wettability of the samples was found to be different with an advancing angle ( advancing) of 123 ± 3.8° for cPnBA0250, while for cPnBA1100 significantly lower values for advancing (111 ± 3.8°) were obtained. First in vitro tests were performed with primary endothelial cells (HUVEC) to study its effects on vascular cell functions. Within the time period of cultivation (72 h), the cells on the cPnBA samples reached subconfluence and showed a viability rate of almost 100%. Although cell density differed after 72 h with more cells on cPnBA0250 than on cPnBA1100, both materials showed no significant effect on the cell morphology, the cellular LDH-release, which was used as marker for the integrity of the cell membrane, and the organisation of the VE-cadherin. However, lower cell density and less actin stress fibre formation on cPnBA1100 might indicate that cell-material interaction was weaker on cPnBA1100 than on cPnBA0250. The secretion of the vasoactive cytokines prostacyclin (PGI2) and thromboxane A2 (TXA2) was low compared to previously reported values. However, the anti-thrombogenic ratio of PGI2/TXA2 - which is balanced under physiological conditions - with much higher PGI2 compared to TXA2 (up to 17.6-fold after 72 h for cPnBA1100) suggests that this material might be effective to preventing thrombosis.

Minipigs are frequently used for scientific research as they are easy to handle and the dimensions of their vascular system do not change after 20 months of age. Although surgical interventions under anaesthesia are often performed in the supine position the effects of this positioning on lung functionality in minipigs have not been systematically described. This study aimed to analyse the influence of supine positioning on the macrostructure of the lung and the pulmonary density by the use of computed tomography imaging in pre-adult Gottingen minipigs. Twelve pre-adult female minipigs were used in the study and lung density was investigated in both the prone and the supine positions. The time between the scans in prone and supine positions was less than 5 minutes (296 ± 6 sec). In the prone position lung density did not differ between the dorsal and ventral part of the lung (-641 ± 72 Hounsfield units [HU]). However in the supine position there was a ventrodorsal gradient of decreasing density (ventral part of the lung: -497 ± 106 HU, dorsal part of the lung: -723 ± 51 HU). The changes in lung density were not accompanied by changes in lung volume (829 ± 191 ml). These results suggest an influence of the body position on the ventilation/perfusion (V(A)/Q) matching of the lung which could possibly result in lowered lung oxygenation as well as in an increased heart activity in the supine position. Additionally, due to the steep course of the vena cava caudalis from the caval foramen in the diaphragm across to the heart (in contrast to the more shallow course in the prone position) the activity of the heart necessary to pump the venous blood to the right atrium has to be higher in the supine position than in the prone position. In pigs the capacity of the heart to increase frequency is limited due to a diastolic/systolic (D/S) ratio

Objective The study aimed to test a Nitinol®-based vein cuff model for external banding valvuloplasty. Method In 12 adult minipigs, the vena jugularis externa was covered for 42 days by a cuff with an inner diameter adapted to the outer vein diameter in supine position. By changing from supine into prone position hypostatically vein dilation was induced to simulate varicose vein dilation. Cuff position and the inner diameter of the vein lumen under the cuff were examined by computer tomography scanning. Also, histological analysis of the vein wall within the cuff was performed. Results The preset tubular shape of the cuff and the cuff position did not change in both prone and supine position, but due to fibrosis the luminal vein diameter within the cuff was decreased ( P < 0.01) already after 21 days. Conclusion A foreign body response resulted in a fibrous capsule covering the cuff which might limit cuff functionality.

Biopolymer-based systems with adjustable macroscopic properties that can be varied in a wide range using only small changes in chemical composition are promising candidates for biomaterial-induced autoregeneration. Glycidylmethacrylated gelatin is photopolymerized with the addition of PEG mono- or dimethacrylate to form co-networks in pH = 7.4 PBS. The degree of swelling (Q) and water uptake (H) in PBS at 37 °C are tailorable for PEGDMA co-networks (Q ≈ 250-650 vol%), while the storage modulus of swollen networks at 3 °C can be adjusted by the PEG(D)MA content (G' = 0.7-145 kPa). Indirect cytotoxicity tests on ethylene oxide sterilized films show non-toxic responses for the homonetwork and all but one PEGDMA-containing co-networks materials.

Degradable polymers are essential to enable biomaterial-based regenerative therapies, particularly, in articular cartilage defect healing, which remains a major clinical challenge. The aim of this study was to investigate the effect of two degradable polymers (as a film or scaffold) on primary articular chondrocytes vitality, adherence, differentiated phenotype and morphology. Films and electro-spun scaffolds were prepared from degradable poly(ether)ester urethane (PDC), which was synthesized via co-condensation of poly(p-dioxanone)diol and poly(e-caprolactone)diol with an aliphatic diisocyanate and poly(p-dioxanone) (PPDO). The thermal and mechanical properties and the surface roughness of the films and scaffolds were examined by differential scanning calorimetry, dynamic mechanical thermal analysis, tensile tests and optical profilometry. Primary porcine articular chondrocytes were seeded on the polymers and analysed for viability, ultrastructure (scanning electron microscopy) and immunolabelled for type II collagen. All films and scaffolds exhibited a low endotoxin load

Biomaterial-induced autoregeneration requires materials with distinct tailored mechanical and thermal properties, water uptake and swelling properties as well as degradation behavior. Furthermore, before any biomaterial can be applied in vivo, in vitro studies should be performed that confirm the suitability for such applications. One facet in this process is the evaluation of endotoxin loads and immunogenic response to the material to avoid an unspecific activation of the immune system, which otherwise might cause fever and could lead to life–threatening pathologies. In this study, gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) were investigated in terms of their endotoxin content and their potential to induce an inflammatory cytokine response in macrophages. Using the Limulus amebocyte lysate (LAL) test it could be shown that the endotoxin content was substantially reduced by using certified low endotoxin containing gelatin and performing the gelatin functionalization under cleanroom conditions. Furthermore, production of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor–alpha (TNFα) of an immune relevant macrophage cell line was significantly reduced for these materials. The survival of the macrophage cell line in the presence of DAT(T)-functionalized gelatins was not influenced by both materials. Therefore, DAT- and DATT-functionalized gelatins were shown to have passed the tests concerning immunological responses important for their applicability in vivo.

Cost effective and safely to apply tissue engineered constructs of big volume bone transplants for the reconstruction of critical sized defects (CSD) are still not available. Key problems with synthetic scaffold materials are shrinkage and fast degradation of the scaffolds, a lack of blood supply and nutrition in the central scaffold volume and the absent or the scarce development of bone tissue along the scaffold to bridge the bone defect. The use of composite scaffolds made of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium phosphates (CaP) revealed promising therapeutical options for the regeneration of critical sized bone defects. In this study interconnectively macroporous PLGA scaffolds loaded with microporous and coated with nanoporous calcium phosphates were either seeded in fixed bed bioreactors with allogenic osteogenically induced mesenchymal stem cells and implanted or implanted unseeded into critical sized femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was excised where the proximal and distal parts of the femur were fixed and stabilized by the use of an eight-hole linear reconstruction plate and secured with three bicortical screws (2.7 mm diameter) on every side of the osteotomy. Aim of the study was if we could find a way to load and coat PLGA scaffolds with CaP so that shrinkage of scaffolds could be avoided, which would favour angiogenesis, blood supply and nutrition in the construct and thus avoid central necroses regularly observed so far in transplants not vascularized and which would be inhabited by cells of he bone lineage forming new bone and healing the defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided and scaffolds were practically not degraded. Both scaffolds, loaded and loaded and coated, revealed blood vessels in all parts of the implants after 4 weeks. Only in scaffolds seeded with allogenic mesenchymal stem cells the development of bridging bone constructs between proximal and distal edges of the femur was observed after four weeks without further supplementation of growth factors. In case of the implantation of non-seeded scaffolds no obvious scaffold bound bone development could be shown.

After intra-arterial administration of radiographic contrast media (RCM), a disorder of the downstream microcirculation both with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure was described. Possible factors contributing to this microcirculatory disorder are increase in plasma viscosity, a formation of echinocytes, a buckling and denudation of endothelial cells, and a disturbation of endothelial prostacyclin release. It is not known so far whether the reactions observed in the context of RCM applications are reactions of venous endothelial cells alone or also of arterial endothelial cells. Therefore, arterial ECs on ECM were exposed to the same RCMs under identical conditions. The decrease of cell-cell contacts with an increase of denuded subendothelial matrix areas in the functionally confluent endothelial cell layer on ECM were more pronounced after a five minute exposure of endothelial cells to Iomeprol compared to Iodixanol. Changes in arterial ECs after the incubation in culture media supplemented with RCM were very subtle in comparison to changes in venous ECs.

Background: Endothelial cells secrete different mediators depending on biochemical and/or biophysical conditions, which can lead to vasodilation or vasoconstriction, respectively. Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. Material and methods: In order to examine, whether such macrocirculatory data might correlate with data obtained in the supplied microvessels, a parallel investigation in the brachial artery (BA) and the supplied nailfold capillaries was performed. The duration and amplitude of the postischemic hyperemia (stasis in the vasculature of the left arm using a blood pressure cuff for 3 minutes) were measured (ultrasound technique) and simultaneously the amplitude and duration of the postischemic hyperemia in ipsilateral nailfold capillaries (intravital capillaroscopy). Results: There was absolutely no correlation between the duration (n = 153, r = 0.076, p = 0.3493) of the diameter increase in the BA and in ipsilateral nailfold capillaries. Conclusion: The regulation of the cutaneous microcirculation did not follow diameter changes of the conduit artery (BA) but seems to be dominated by the precapillary arterioles.

In cardiac surgery the substitution of lost blood volume by plasma substitutes is a common therapeutical approach. None of the currently available blood substitutes has a sufficient oxygen transport capacity. This can limit the functional integrity of the myocardium known as highly oxygen consumptive. The study was aimed to get information about the minimal hematocrit, also known as critical hematocrit (cHct), which guarantees a stable and adequate oxygen partial pressure in the myocardium (pO2). In adult female pigs (n = 7) the hematocrit was reduced by isovolemic blood dilution with an intravenous infusion of isotonic 4% gelatine polysuccinate solution, The substituted blood volume ranged between 3000 ml and 7780 ml (mean: 5254 ± 1672 ml). In all animals the pO2 of the myocardium of the beating heart and of the resting skeletal muscle increased until blood dilution resulted in a Hct decrease down to 15%. Further blood dilution resulted in a decrease of the pO2. Only after the Hct was < 10% the pO2 was lower than before blood dilution and accompanied by a lethal ischemia of the myocardium. These data indicate a cHct of about 10% in the pig animal model.

Mechanical conditioning can serve as a potent tool to influence mechano-responsive cells, which plays a prominent role during formation and regeneration of functional tissue. Recently, the differentiation of mesenchymal stem cells could be influenced by the local stiffness of hydrogels used as 2D substrates. However, the mechanical properties and the swellability of hydrogels in physiological liquids are difficult to control precisely as their properties strongly depend on physical parameters like ionic strength or pH value. Here, we explored amorphous, hydrophobic poly(n-butyl acrylate) networks (cPnBA) as soft substrates for cell culture system with adjustable mechanical properties. cPnBAs were synthesized via bulk radical polymerization from n-butyl acrylate (nBA) and poly(propylene glycol) dimethacrylate (PPGDMA) as crosslinker. The Young's modulus for cPnBAs determined by tensile tests could be systematically adjusted from 100 kPa to 10 MPa by increasing the PPGDMA-content at ambient temperature, while the glass transition temperature (Tg) was found to increase from −46 to −22°C. All cPnBAs exhibited similar surface properties with a surface roughness (Rq) in the range from 1.4 to 0.4 µm and advancing contact angles from 115° to 100°, which remained constant after ethylene oxide sterilization. The extracts of sterilized materials were tested for cytotoxic effects with L929 cells. All tested samples were non-cytotoxic. The functional integrity of cell membranes and mitochondrial activity stayed unaffected. The investigated polymer networks are promising candidates as soft substrates for passive mechanical stimulation of cells in vitro in cell culture devices or in vivo as implant coatings. Copyright © 2010 John Wiley & Sons, Ltd.

Polymer-coated and polymer-based cardiovascular implants are essential constituents of modern medicine and will proceed to gain importance with the demographic changes toward a society of increasing age-related morbidity. Based on the experiences with implants such as coronary or peripheral stents, which are presently widely used in clinical medicine, several properties of the next generation of cardiovascular implants have been envisioned that could be fulfilled by multifunctional polymers. The challenge is to combine tailored mechanical properties and rapid endothelialization with controlled drug release in order to modulate environmental cells and tissue. Additionally, degradability and sensitivity to external stimuli are useful in several applications. A critical function in terms of clinical complications is the hemocompatibility. The design of devices with improved hemocompatibility requires advancedin vitrotest setups as discussed in depth in this article. Finally, degradable, multifunctional shape-memory polymers are introduced as a promising family of functional polymers that fulfill several requirements of modern implants and are of high relevance for cardiovascular application (e.g., stent technology). Such multifunctional polymers are a technology platform for future cardiovascular implants enabling induced autoregeneration in regenerative therapies.

Isoforms of the enzyme lactate dehydrogenase (LDH) were found in almost all cells of the organism and an elevated activity of LDH in the circulation is thought to be a clear indicator of elevated cell destruction coinciding with an increased release of components from the cellular cytoplasm, e.g. LDH. Here, we report on an in-vitro examination to test whether radiographic contrast media (RCM) could induce cell destruction followed by an increase in LDH release. The RCM were tested in non-flow cultures of human umbilical venous endothelial cells (HUVEC) of the fourth passage seeded on extracellular matrix and the results were compared to those from control cultures not exposed to contrast media. The examination revealed that the addition of contrast media to the cell culture media supplemented with pooled human serum (HSP) as source of exogenous LDH was followed by a strong decrease in LDH activity both in the absence and presence of HUVEC. Within 1.5 min after the addition of contrast media to the culture medium supplemented with HSP (30% vol of the culture medium were replaced by either of two contrast media, Iodixanol or Iopromide) the LDH activity decreased about 80% compared to the initial values. In contrast, the LDH activity did not change in cell culture media not supplemented with RCM. The partial replacement of HSP supplemented cell culture medium by RCM will cause a dilution of cell culture medium constituents. The decrease of LDH activity, however, was much stronger than the decrease thought to be attributable to the effects of dilution of cell culture medium, so that the role of dilution seems to be a minor one in this case. It has to be assumed that the RCM could interact with the LDH available in the culture medium as well as with the substrates delivered with the measurement system for the assessment of LDH activity, so that both, the amount of LDH and the activities of enzymes involved might be influenced. In the presence of HUVEC a similar effect was observed. Here, a little less strong decrease of LDH activity occurred compared to the decrease in cell culture medium without HUVEC. This was unexpected because a considerable amount of HUVEC were detached after the addition of contrast media and many of these cells were damaged seriously so that a significant amount of endogenous LDH should have been released. These unexpected results make it necessary to re-evaluate those past time examinations focussed on cell damage/destruction in the presence of contrast media, where the measurement of LDH activity was used as indicator or cell vitality and where cell decease rates were correlated to questionable toxic influences. According to the results of the examination reported here it is difficult to uphold the interpretation of recently published findings that contrast media almost exclusively induce cellular apoptosis and not necrosis.

Multiblock copolymers with shape-memory capability attracted tremendous interest as promising candidate materials for smart, degradable implants. In the present study the hen's egg-chorioallantoic membrane test (HET-CAM test) was used to investigate the angiogenic properties of a thermoplastic, biodegradable multiblock copolymer PDC composed of poly (p-dioxanone) hard segments (PPDO) and crystallizable poly(s-caprolactone) switching segments (PCL), whereby PPDO and PCL homopolymers were investigated as controls. According to our HET-CAM test data, only PDC induced significant microvessel attraction and formation in the contact area of the test specimen after 48 hours of incubation showing newly formed blood vessels along the outer edge of the material. In contrast, no newly formed blood vessels were observed around the PPDO or PCL specimen after the same incubation period. These in vivo results indicate that the multiblock copolymer PDC possibly possesses an angiogenic effect and it can induce blood vessel formation in its direct vicinity when it is implanted in vivo.

It is a great honor for me to receive the Fahraeus Award and I would like to thank the European Society very much for this. The medal represents an important milestone in my life and to have achieved it fills me with immense joy. I was especially pleased that my laudation was held by Mike Rampling – whom I had the pleasure of presenting the Fahraeus medal in Dresden – and that this year it was his turn to present it to me. Mike is a very good friend of mine and an outstanding personality. I have always enjoyed the articles he has published and the lectures he has given over the past years. To be honored with the Fahraeus medal as a non-physician was only possible due to my close collaborative research relationship with many clinicians within a vast network. Therefore, my most sincere thanks go to all with whom I had the pleasure of working during the past 25 years. As has been the tradition for many years, I would now like to present some of the most important of my work projects. My first work in the field of hemorheology was to investigate under which conditions the HagenPoiseuille Law is valid. This question can be answered straightforwardly by continuum physics. General mass and impulse balance equations form coupled systems of partial differential equations that are not directly solvable with respect to the associated exit, transient and boundary conditions.

This study shows first in vitro tests of a nitinol based vein cuff developed for external valvuloplasty. In contrary to currently existing vein cuffs the tested model enables minimal invasive implantation and also maintains its round pre-shaped profile at body temperature (37 degrees C). The examination of the cuff surface structure by scanning electron microscopy, profilometry and X-ray photoelectron spectroscopy after sterilization with ethylene oxide and before cyto-compatibility testing revealed a nearly smooth surface (mean square roughness Rq 66 +/- 33 nm) which was primarily composed of nickel, oxygen, titanium, carbon and silicon where nickel was the least fraction (Ni: 0.7%, Ti: 1.7%, Si: 15.8%, O: 29.5%, C: 52.3%) of the surface elements. Si and C are supposed to be contaminations caused by a final cuff polishing with silicon carbide at the end of the manufacturing process. To evaluate cyto-compatibility initial cell adherence and cell activity were assessed. The results showed good initial cell adherence of L929 fibroblast-like cells on the cuff surface already after 24 h. The results also revealed no inhibitory effects on the activity of these cells (MTS test) later on. The test setup developed to analyse functionality in a dynamic mode was shown to be suited at blood pressures up to 300 mmHg. The cuff successfully limited dilation of varicose veins (Vena saphena magna) at physiological blood pressures (< 120 mmHg) and also in cases of hypertonia (300 mmHg) to the diameter determined by the cuff (4.0 mm) over thecomplete testing period. This indicates that the clasp based cuff closure mechanism is suited to close the cuff under variable physiological and pathological blood pressure conditions. The cuff structure only allowed minimal adaptation on the inhomogenously dilating vein profile in the both peripheral cuff modules. Both peripheral modules followed the vessel dilation in correlation to the applied pressure. At pressures within the physiological range