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Dive into the research topics where Niels Grabow is active.

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Featured researches published by Niels Grabow.


Journal of Biomechanical Engineering-transactions of The Asme | 2005

Mechanical properties of laser cut poly(L-lactide) micro-specimens: implications for stent design, manufacture, and sterilization.

Niels Grabow; Martin Schlun; Katrin Sternberg; Nico Hakansson; Sven Kramer; Klaus-Peter Schmitz

BACKGROUND The development of endoluminal stents from polymeric materials requires an understanding of the basic mechanical properties of the polymer and the effects of manufacturing and sterilization on those properties. METHODS Pure poly(L-lactide) (PLLA) and PLLA containing varying amounts of triethylcitrate (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast and CO2 laser-cut. Specimen dimensions were adapted to the strut size of polymeric vascular stents. The properties of the PLLA micro-specimens were assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and gamma-irradiation). Tensile tests, and creep and recovery tests were carried out at 37 degrees C. Additionally the thermal and thermo-mechanical characteristics were investigated using dynamic-mechanical analysis (DMA) and differential scanning calorimetry (DSC). RESULTS The results showed the dramatic influence of the plasticizer content and sterilization procedure on the mechanical properties of the material. Laser cutting had a lesser effect. Hence the effects of processing and sterilization must not be overlooked in the material selection and design phases of the development process leading to clinical use. Altogether, the results of these studies provide a clearer understanding of the complex interaction between the laser machining process and terminal sterilization on the primary mechanical properties of PLLA and PLLA plasticized with TEC.


Journal of Endovascular Therapy | 2007

A biodegradable stent based on poly(L-lactide) and poly(4-hydroxybutyrate) for peripheral vascular application: preliminary experience in the pig.

C.M. Bünger; Niels Grabow; Katrin Sternberg; Martin Goosmann; Klaus-Peter Schmitz; Hans J. Kreutzer; Hüseyin Ince; Stefan Kische; Christoph Nienaber; David P. Martin; Simon F. Williams; Ernst Klar; Wolfgang Schareck

Purpose: To assess the technical feasibility and biocompatibility of a novel stent based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for peripheral vascular applications. Methods: A polytetrafluoroethylene aortobi-iliac graft was implanted in 5 pigs through a midline abdominal incision. After transverse graft limb incision, 5 PLLA/P4HB stents and 5 metal stents (316L stainless steel) were randomly deployed at both iliac anastomotic sites with 6-mm balloon catheters. Angiography was performed to determine patency prior to sacrifice at 6 weeks. Stented segments were surgically explanted and processed for quantitative histomorphometry. Vascular injury and inflammation scores were assigned to the stented iliac segments. Results: No animals were lost during follow-up. All PLLA/P4HB stents were deployed within 2 minutes by balloon inflation to 8 bars without rupture of the stent struts or anastomotic suture. All stents were patent on postprocedural angiography. Histological analysis showed no signs of excessive recoiling or collapse. PLLA/P4HB stents demonstrated decreased residual lumen area and increased neointimal area after 6 weeks (12.27±0.62 and 8.40±1.03 mm2, respectively) compared to 316L stents (13.54±0.84 and 6.90±1.11 mm2, respectively) as the result of differences in stent areas (PLLA/P4HB: 4.31±0.15 mm2; 316L: 2.73±0.29 mm2). Vascular injury scores showed only mild vascular trauma for all stents (PLLA/P4HB: 0.41±0.59; 316L: 0.32±0.47). Inflammatory reaction was slightly higher around PLLA/P4HB stent struts (1.39±0.52) compared to 316L (1.09±0.50). Conclusion: Rapid balloon expansion of PLLA/P4HB stents is feasible without risk of strut rupture. PLLA/P4HB stents provide adequate mechanical stability after iliac anastomotic stenting in pigs. Smaller residual luminal areas in the PLLA/P4HB stents might have been caused by tissue ingrowth into the larger strut interspaces due to higher strut thickness (stent area) in this group. This limitation needs to be addressed in future work on the stent design.


Journal of Endovascular Therapy | 2006

Iliac Anastomotic Stenting with a Sirolimus-Eluting Biodegradable Poly-L-Lactide Stent: A Preliminary Study after 6 Weeks

C.M. Bünger; Niels Grabow; Christina Kröger; Björn Lorenzen; Karlheinz Hauenstein; Martin Goosmann; Klaus-Peter Schmitz; Hans J. Kreutzer; Daniel Lootz; Hüseyin Ince; Christoph Nienaber; Ernst Klar; Wolfgang Schareck; Katrin Sternberg

Purpose: To assess technical feasibility and biocompatibility of a new biodegradable sirolimus-eluting poly-L-lactide (PLLA) vascular anastomotic stent. Methods: A polytetrafluoroethylene bifurcated graft was implanted in 9 pigs through a midline abdominal incision. After transverse graft limb incision, 6 unloaded PLLAs, 6 sirolimus-loaded PLLAs, and 6 unloaded stainless steel (316L) stents were randomly implanted at both iliac anastomotic sites. Stents were deployed with a 6-mm balloon under direct vision without the use of angiography. Prior to sacrifice after 6 weeks, contrast-enhanced computed tomography (CT) was performed to determine patency of the target vessels. Stented segments were surgically explanted and processed for histology to measure the mean luminal diameter and intimal thickness and to assign vascular injury and inflammation scores. Results: No animals were lost during the study period. All stented graft limbs were patent on CT and histology. At the anastomotic sites and iliac arteries, the mean luminal diameter of SIR-PLLA stents (4.11±0.15 and 4.08±0.13 mm, respectively) were comparable to metal stents (4.23±0.35 and 4.21±0.26 mm, respectively), but significantly higher compared to unloaded PLLA stents [3.32±0.56 mm (p<0.001) and 3.29±0.39 mm (p=0.013), respectively]. At the iliac arteries, the mean intimal thickness was significantly lower with SIR-PLLA stents (0.09±0.02 mm) compared to unloaded PLLA stents (0.31±0.15 mm, p<0.001) and metal stents (0.19±0.04 mm, p=0.004). Vascular injury scores demonstrated only mild vascular trauma for all stents (SIR-PLLA: 0.42±0.63, PLLA: 0.51±0.62, metal: 0.50±0.62). Only mild inflammatory reaction was noted around SIR-PLLA stent struts (1.14±0.46), which was comparable to metal stents (1.27±0.45) but significantly lower than PLLA stents (1.79±0.56, p<0.001). Conclusion: SIR-PLLA stents showed comparable luminal diameter compared to metal stents, so incorporating sirolimus could reduce the inflammatory and neointimal response to PLLA stents. These findings need to be assessed with longer follow-up to confirm maintenance of efficacy.


European Journal of Pharmaceutics and Biopharmaceutics | 2011

Examination of drug release and distribution from drug-eluting stents with a vessel-simulating flow-through cell

Anne Seidlitz; Stefan Nagel; Beatrice Semmling; Niels Grabow; H. Martin; Volkmar Senz; Claus Harder; Katrin Sternberg; Klaus-Peter Schmitz; Heyo K. Kroemer; Werner Weitschies

The recently introduced vessel-simulating flow-through cell offers new possibilities to examine the release from drug-eluting stents in vitro. In comparison with standard dissolution methods, the additional compartment allows for the examination of distribution processes and creates dissolution conditions which simulate the physiological situation at the site of implantation. It was shown previously that these conditions have a distinct influence on the release rate from the stent coating. In this work, different preparation techniques were developed to examine the spatial distribution within the compartment simulating the vessel wall. These methods allowed for the examination of diffusion depth and the distribution resulting in the innermost layer of the compartment simulating the vessel wall. Furthermore, the in vitro release and distribution examined experimentally were modelled mathematically using finite element (FE) methods to gain further insight into the release and distribution behaviour. The FE modelling employing the experimentally determined diffusion coefficients yielded a good general description of the experimental data. The results of the modelling also provided important indications that inhomogeneous coating layer thicknesses around the strut may result from the coating process which influence release and distribution behaviour. Taken together, the vessel-simulating flow-through cell in combination with FE modelling represents a unique method to analyse drug release and distribution from drug-eluting stents in vitro with particular opportunities regarding the examination of spatial distributions within the vessel-simulating compartment.


Journal of Biomedical Materials Research Part B | 2012

Magnesium used in bioabsorbable stents controls smooth muscle cell proliferation and stimulates endothelial cells in vitro.

Katrin Sternberg; Matthias Gratz; Kathleen Koeck; Joerg Mostertz; Robert Begunk; Marian Loebler; Beatrice Semmling; Anne Seidlitz; Petra Hildebrandt; Georg Homuth; Niels Grabow; Conny Tuemmler; Werner Weitschies; Klaus-Peter Schmitz; Heyo K. Kroemer

Magnesium-based bioabsorbable cardiovascular stents have been developed to overcome limitations of permanent metallic stents, such as late stent thrombosis. During stent degradation, endothelial and smooth muscle cells will be exposed to locally high magnesium concentrations with yet unknown physiological consequences. Here, we investigated the effects of elevated magnesium concentrations on human coronary artery endothelial and smooth muscle cell (HCAEC, HCASMC) growth and gene expression. In the course of 24 h after incubation with magnesium chloride solutions (1 or 10 mM) intracellular magnesium level in HCASMC raised from 0.55 ± 0.25 mM (1 mM) to 1.38 ± 0.95 mM (10 mM), while no increase was detected in HCAEC. Accordingly, a DNA microarray-based study identified 69 magnesium regulated transcripts in HCAEC, but 2172 magnesium regulated transcripts in HCASMC. Notably, a significant regulation of various growth factors and extracellular matrix components was observed. In contrast, viability and proliferation of HCAEC were increased at concentrations of up to 25 mM magnesium chloride, while in HCASMC viability and proliferation appeared to be unaffected. Taken together, our data indicate that magnesium halts smooth muscle cell proliferation and stimulates endothelial cell proliferation, which might translate into a beneficial effect in the setting of stent associated vascular injury.


Journal of Biomedical Materials Research Part B | 2011

Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery.

Marian Löbler; Katrin Sternberg; Oliver Stachs; Reto Allemann; Niels Grabow; Anne Roock; Christine F. Kreiner; Detlef Streufert; Axel T. Neffe; Bui Duc Hanh; Andreas Lendlein; Klaus-Peter Schmitz; Rudolf Guthoff

Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 μm outer and 200 μm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems.


Biomedizinische Technik | 2013

Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications.

Katrin Sternberg; Svea Petersen; Niels Grabow; Volkmar Senz; Henriette E. Meyer zu Schwabedissen; Heyo K. Kroemer; Klaus-Peter Schmitz

Abstract Implants providing controlled, local release of active substances are of interest in different medical applications. Therefore, the focus of the present article is the development of implant-associated diffusion- or chemically controlled local drug delivery (LDD) systems based on biodegradable polymeric drug carriers. In this context, we provide new data and review our own recently published data concerning the drug release behavior of diffusion-controlled LDD systems in relation to the kind of polymer, drug content, coating mass/thickness, and layer composition. We demonstrate that polymers allow a wide range of control over the drug release characteristics. In this regard, we show that the glass transition temperature of a polymer has an impact on its drug release. Additionally, the blending of hydrophobic, semicrystalline polymers with amorphous polymers leads to an increase in the rate of drug release compared with the pure semicrystalline polymer. Moreover, the percentage loading of the embedded drug has a considerable effect on the rate and duration of drug release. Furthermore, we discuss chemically controlled LDD systems designed for the release of biomolecules, such as growth factors, as well as nanoparticle-mediated LDD systems. With our own published data on drug-eluting stents, microstents, and cochlear implants, we highlight exemplary implant-associated LDD systems designed to improve implant performance through the reduction of undesirable effects such as in-stent restenosis and fibrosis.


Current Pharmaceutical Biotechnology | 2013

Advances in coronary stent technology--active drug-loaded stent surfaces for prevention of restenosis and improvement of biocompatibility.

Katrin Sternberg; Niels Grabow; Svea Petersen; Werner Weitschies; Claus Harder; Hüseyin Ince; Heyo K. Kroemer; Klaus-Peter Schmitz

Beyond their originally sole mechanical function, current drug-eluting stents (DES) implement the concept of local drug delivery for the re-opening of stenotic arterial vessels, and for prevention of in-stent restenosis as one of the major limitations of conventional bare metal stents (BMS). Current DES consist of a permanent metallic stent platform and an active agent being released from a drug-incorporated polymer coating or a porous stent surface. Although DES have impressively demonstrated their capability of reducing in-stent restenosis, their safety remains under debate due to potential risks, such as delayed healing, late thrombosis and hypersensitivity demanding further development. Current advancements in the stent design address the stent platform, the pharmacologically active substance and/or the drug carrier. For instance, novel biocompatible absorbable stent platforms and drug carriers are developed and novel drugs with a differential effect on vascular endothelial and smooth muscle cells, providing efficient inhibition of muscle cells without altering the endothelial cell function, are identified. Moreover, biofunctionalization of the stents surface with capture molecules for endothelial progenitor cells are under investigation in order to achieve an in situ endothelialization of the implant. In this context, this review paper discusses the current advances in coronary stent technology with a special focus on novel stent platforms, drugs and stent coatings for the prevention of restenosis and improvement of biocompatibility.


Journal of Endovascular Therapy | 2006

Iliac Anastomotic Stenting with a Biodegradable Poly-L-Lactide Stent: A Preliminary Study after 1 and 6 Weeks

C.M. Bünger; Niels Grabow; Katrin Sternberg; Lisa Ketner; Christina Kröger; Björn Lorenzen; Karlheinz Hauenstein; Klaus-Peter Schmitz; Hans J. Kreutzer; Daniel Lootz; Hüseyin Ince; Christoph Nienaber; Ernst Klar; Wolfgang Schareck

Purpose: To assess the technical feasibility, thrombogenicity, and biocompatibility of a new biodegradable poly-L-lactic acid (PLLA) anastomotic stent. Methods: A polytetrafluoroethylene bifurcated graft was implanted in 17 pigs through a midline abdominal incision. After transverse graft incision, 17 316L stainless steel stents and 17 PLLA stents were randomly implanted at both iliac anastomotic sites and deployed with a 6-mm balloon under direct vision without angiography. Intended follow-up was 1 week in 6 pigs receiving oral acetylsalicylic acid (ASA) and in 7 pigs receiving ASA/clopidogrel; 4 pigs receiving ASA/clopidogrel were followed for 6 weeks. At the end of the study, the segments containing the stents were surgically explanted and processed for histology to measure the mean luminal diameter, intimal thickness, and the vascular injury and inflammation scores. Results: Initial technical success of stent placement was achieved in all animals without rupture of the suture. Two pigs died (unrelated to the stent) at 3 days after operation (1 in groups A and B). At 1 week, all PLLA stents showed thrombotic occlusion with the use of ASA alone. In contrast, all PLLA stents remained patent with concurrent administration of ASA/clopidogrel. All metal stents were patent regardless of the antiplatelet regimen. The mean luminal diameter of patent PLLA stents (4.13±0.17 mm) was comparable to metal stents (4.27±0.35 mm, p=0.78) at 1 week, but significantly diminished at 6 weeks (3.21±0.44 versus 4.19±0.18 mm, p=0.005). Histological analysis showed no signs of excessive recoil. PLLA stents induced a higher inflammation score (1.79±0.56) and more intimal hyperplasia (0.34±0.11 mm) compared to metal stents [1.27±0.44 mm (p<0.001) and 0.18±0.04 mm (p=0.006), respectively] at 6 weeks. Vascular injury was comparable between PLLA and metal stents. Conclusion: Biodegradable PLLA stents showed higher thrombogenicity and reduced patency compared to metal stents during early follow-up. Although ASA and clopidogrel prevented thrombotic occlusion, the increased inflammatory response and neointima formation remain major concerns of PLLA stents. A solution to this problem might be the incorporation of anti-inflammatory drugs into the PLLA stent.


Biomedizinische Technik | 2002

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

Niels Grabow; H. Martin; K.-P. Schmitz

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.

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H. Martin

University of Rostock

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