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Hussain A.F.,Institute of Applied Medical Engineering | Kampmeier F.,Institute of Applied Medical Engineering | Von Felbert V.,RWTH Aachen | Merk H.-F.,RWTH Aachen | And 2 more authors.
Bioconjugate Chemistry | Year: 2011

Cancer cells can be killed by photosensitizing agents that induce toxic effects when exposed to nonhazardous light, but this also causes significant damage to surrounding healthy cells. The specificity of photodynamic therapy can be increased by conjugating photosensitizing agents to antibodies and antibody fragments that bind specifically to tumor cell antigens. However, standard conjugation reactions produce heterogeneous products whose targeting specificity and spectroscopic properties can be compromised. In this study, we used an antibody fragment (scFv-425) that binds to the epidermal growth factor receptor (EGFR) as a model to investigate the use of SNAP-tag fusions as an improved conjugation strategy. The scFv-425-SNAP-tag fusion protein allowed the specific conjugation of a chlorin e6 photosensitizer modified with O(6)-benzylguanine, generating a homogeneous product that was delivered specifically to EGFR + cancer cells and resulted in significant, tumor cell-specific cytotoxicity. The impact of our results on the development of photodynamic therapy is discussed. © 2011 American Chemical Society. Source


Hussain A.F.,Institute of Applied Medical Engineering | Tur M.K.,Justus Liebig University | Barth S.,Institute of Applied Medical Engineering | Barth S.,Fraunhofer Institute for Molecular Biology and Applied Ecology
Nucleic Acid Therapeutics | Year: 2013

Small interfering RNAs (siRNAs) silence gene expression by triggering the sequence-specific degradation of mRNAs, but the targeted delivery of such reagents remains challenging and a significant obstacle to therapeutic applications. One promising approach is the use of RNA aptamers that bind tumor-associated antigens to achieve the delivery of siRNAs to tumor cells displaying specific antigens. Wholly RNA-based constructs are advantageous because they are inexpensive to synthesize and their immunogenicity is low. We therefore joined an aptamer-recognizing alpha V and integrin beta 3 (αvβ3) integrin to a siRNA that targets eukaryotic elongation factor 2 and achieved for the first time the targeted delivery of a siRNA to tumor cells expressing αvβ3 integrin, causing the inhibition of cell proliferation and the induction of apoptosis specifically in tumor cells. The impact of our results on the development of therapeutic aptamer-siRNA constructs is discussed. © Copyright 2013, Mary Ann Liebert, Inc. Source


McGrath D.J.,Biomechanics Research Center | O'Brien B.,Biomechanics Research Center | Bruzzi M.,Biomechanics Research Center | Kelly N.,Biomechanics Research Center | And 3 more authors.
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2016

Covered tracheobronchial stents are used to prevent tumour growth from reoccluding the airways. In the present work a combination of experimental and computational methods are used to present the mechanical effects that adhered covers can have on stent performance. A prototype tracheobronchial stent is characterised in bare and covered configurations using radial force, flat plate and a novel non-uniform radial force test, while computational modelling is performed in parallel to extensively inform the physical testing. Results of the study show that cover configuration can have a significant structural effect on stent performance, and that stent response (bare or covered) is especially loading specific, highlighting that the loading configuration that a stent is about to be subjected to should be considered before stent implantation. © 2016 Elsevier Ltd. Source


Amaral F.,Institute of Applied Medical Engineering | Gross-Hardt S.,Institute of Applied Medical Engineering | Timms D.,Clinical and Engineering Management | Egger C.,Institute of Applied Medical Engineering | And 2 more authors.
Artificial Organs | Year: 2013

The rapid evolution of rotary blood pump (RBP) technology in the last few decades was shaped by devices with increased durability, frequently employing magnetic or hydrodynamic suspension techniques. However, the potential for low flow in small gaps between the rotor and pump casing is still a problem for hemocompatibility. In this study, a spiral groove hydrodynamic bearing (SGB) is applied with two distinct objectives: first, as a mechanism to enhance the washout in the secondary flow path of a centrifugal RBP, lowering the exposure to high shear stresses and avoiding thrombus formation; and second, as a way to allow smaller gaps without compromising the washout, enhancing the overall pump efficiency. Computational fluid dynamics was applied and verified via bench-top experiments. An optimization of selected geometric parameters (groove angle, width and depth) focusing on the washout in the gap rather than generating suspension force was conducted. An optimized SGB geometry reduced the residence time of the cells in the gap from 31 to 27ms, an improvement of 14% compared with the baseline geometry of 200μm without grooves. When optimizing for pump performance, a 15% smaller gap yielded a slightly better rate of fluid exchange compared with the baseline, followed by a 22% reduction in the volumetric loss from the primary pathway. Finally, an improved washout can be achieved in a pulsatile environment due to the SGB ability to pump inwardly, even in the absence of a pressure head. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation. Source


Neidlin M.,Institute of Applied Medical Engineering | Steinseifer U.,Institute of Applied Medical Engineering | Kaufmann T.A.S.,Institute of Applied Medical Engineering
Journal of Biomechanics | Year: 2014

Neurological complication often occurs during cardiopulmonary bypass (CPB). One of the main causes is hypoperfusion of the cerebral tissue affected by the position of the cannula tip and diminished cerebral autoregulation (CA). Recently, a lumped parameter approach could describe the baroreflex, one of the main mechanisms of cerebral autoregulation, in a computational fluid dynamics (CFD) study of CPB. However, the cerebral blood flow (CBF) was overestimated and the physiological meaning of the variables and their impact on the model was unknown. In this study, we use a 0-D control circuit representation of the Baroreflex mechanism, to assess the parameters with respect to their physiological meaning and their influence on CBF. Afterwards the parameters are transferred to 3D-CFD and the static and dynamic behavior of cerebral autoregulation is investigated.The parameters of the baroreflex mechanism can reproduce normotensive, hypertensive and impaired autoregulation behavior. Further on, the proposed model can mimic the effects of anesthetic agents and other factors controlling dynamic CA. The CFD simulations deliver similar results of static and dynamic CBF as the 0-D control circuit. This study shows the feasibility of a multiscale 0-D/3-D approach to include patient-specific cerebral autoregulation into CFD studies. © 2014 Elsevier Ltd. Source

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