The Experts below are selected from a list of 5661 Experts worldwide ranked by ideXlab platform
Hongyuan Chen - One of the best experts on this subject based on the ideXlab platform.
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a photoelectrochemical sensor based on cds polyamidoamine nano composite film for Cell Capture and detection
Biosensors and Bioelectronics, 2010Co-Authors: Zheng Qian, Jingjuan Xu, Guangli Wang, Hongyuan ChenAbstract:Abstract We demonstrated herein a newly developed photoelectrochemical Cell-sensor for the determination of SMMC-7721 human hepatoma carcinoma Cells (SMMC-7721 Cells) by using a photosensitive CdS-polyamidoamine (G4) nano-composite film (CdS-PAMAM). The film was generated by electrodeposition method. The presence of PAMAM in the film eliminated the surface defects of CdS nanoparticles and therefore resulted in a greatly enhanced photocurrent and a reduced dark current. In the presence of the electron donor ascorbic acid (AA), the photoexcitation of this modified electrode potentiostated at 0 V versus Ag/AgCl led to an anodic photocurrent. As a result of the covalent coupling reactions, a layer of concanavalin A (ConA) was firmly bound to the functionalized CdS-PAMAM film via glutaraldehyde bridges. The resulting modified electrodes were tested as sensors for SMMC-7721 Cell Capture and detection via affinity interactions between ConA and mannosyl groups on Cell surface. The Cell concentration was measured from 5.0 × 10 3 to 1.0 × 10 7 Cells mL −1 through the decrease in photocurrent intensity resulting from its specific binding onto the photosensitive film, the detection limit being 5.0 × 10 3 Cells mL −1 .
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a reusable interface constructed by 3 aminophenylboronic acid functionalized multiwalled carbon nanotubes for Cell Capture release and cytosensing
Advanced Functional Materials, 2010Co-Authors: Xue Zhong, Jingjuan Xu, Hongyuan ChenAbstract:A newly developed electrochemical Cell sensor for the determination of K562 leukemia Cells using 3-aminophenylboronic acid (APBA)-functionalized multiwalled carbon nanotubes (MWCNTs) films is demonstrated. The films are generated by the covalent coupling between the NH2 groups in APBA and the COOH group in the acid-oxidized MWCNTs. As a result of the sugar-specific affinity interactions, the K562 leukemia Cells are firmly bound to the APBA-functionalized MWCNTs film via boronic acid groups. Compared to electropolymerized APBA films, the presence of MWCNTs not only provides abundant boronic acid domains for Cell Capture, their high electrical conductivity also makes the film suitable for electrochemical sensing applications. The resulting modified electrodes are tested as Cell detection sensors. This work presents a promising platform for effective Cell Capture and constructing reusable cytosensors.
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A Reusable Interface Constructed by 3‐Aminophenylboronic Acid‐Functionalized Multiwalled Carbon Nanotubes for Cell Capture, Release, and Cytosensing
Advanced Functional Materials, 2010Co-Authors: Xue Zhong, Jingjuan Xu, Hongyuan ChenAbstract:A newly developed electrochemical Cell sensor for the determination of K562 leukemia Cells using 3-aminophenylboronic acid (APBA)-functionalized multiwalled carbon nanotubes (MWCNTs) films is demonstrated. The films are generated by the covalent coupling between the NH2 groups in APBA and the COOH group in the acid-oxidized MWCNTs. As a result of the sugar-specific affinity interactions, the K562 leukemia Cells are firmly bound to the APBA-functionalized MWCNTs film via boronic acid groups. Compared to electropolymerized APBA films, the presence of MWCNTs not only provides abundant boronic acid domains for Cell Capture, their high electrical conductivity also makes the film suitable for electrochemical sensing applications. The resulting modified electrodes are tested as Cell detection sensors. This work presents a promising platform for effective Cell Capture and constructing reusable cytosensors.
Mehmet Toner - One of the best experts on this subject based on the ideXlab platform.
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flexible octopus shaped hydrogel particles for specific Cell Capture
Small, 2016Co-Authors: Lynna Chen, Mehmet Toner, Harry Z An, Ramin Haghgooie, Aaron T Shank, Joseph M Martel, Patrick S DoyleAbstract:Multiarm hydrogel microparticles with varying geometry are fabricated to specifically Capture Cells expressing epithelial Cell adhesion molecule. Results show that particle shape influences Cell-Capture efficiency due to differences in surface area, hydrodynamic effects, and steric constraints. These findings can lead to improved particle design for Cell separation and diagnostic applications.
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Flexible Octopus‐Shaped Hydrogel Particles for Specific Cell Capture
Small, 2016Co-Authors: Lynna Chen, Mehmet Toner, Harry Z An, Ramin Haghgooie, Aaron T Shank, Joseph M Martel, Patrick S DoyleAbstract:Multiarm hydrogel microparticles with varying geometry are fabricated to specifically Capture Cells expressing epithelial Cell adhesion molecule. Results show that particle shape influences Cell-Capture efficiency due to differences in surface area, hydrodynamic effects, and steric constraints. These findings can lead to improved particle design for Cell separation and diagnostic applications.
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discontinuous nanoporous membranes reduce non specific fouling for immunoaffinity Cell Capture
Small, 2013Co-Authors: Sukant Mittal, Ian Y Wong, William M Deen, Mehmet Toner, Ahmet Ali YanikAbstract:The microfluidic isolation of target Cells using adhesion-based surface Capture has been widely explored for biology and medicine. However, high-throughput processing can be challenging due to interfacial limitations such as transport, reaction, and non-specific fouling. Here, it is shown that antibody-functionalized Capture surfaces with discontinuous permeability enable efficient target Cell Capture at high flow rates by decreasing fouling. Experimental characterization and theoretical modeling reveal that “wall effects” affect Cell–surface interactions and promote excess surface accumulation. These issues are partially circumvented by reducing the transport and deposition of Cells near the channel walls. Optimized microfluidic devices can be operated at higher Cell concentrations with significant improvements in throughput.
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Discontinuous Nanoporous Membranes Reduce Non‐Specific Fouling for Immunoaffinity Cell Capture
Small, 2013Co-Authors: Sukant Mittal, Ian Y Wong, William M Deen, Ahmet Ali Yanik, Mehmet TonerAbstract:The microfluidic isolation of target Cells using adhesion-based surface Capture has been widely explored for biology and medicine. However, high-throughput processing can be challenging due to interfacial limitations such as transport, reaction, and non-specific fouling. Here, it is shown that antibody-functionalized Capture surfaces with discontinuous permeability enable efficient target Cell Capture at high flow rates by decreasing fouling. Experimental characterization and theoretical modeling reveal that “wall effects” affect Cell–surface interactions and promote excess surface accumulation. These issues are partially circumvented by reducing the transport and deposition of Cells near the channel walls. Optimized microfluidic devices can be operated at higher Cell concentrations with significant improvements in throughput.
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biopolymer system for Cell recovery from microfluidic Cell Capture devices
Analytical Chemistry, 2012Co-Authors: Ajay Shah, Min Yu, Zev Nakamura, Jordan C Ciciliano, Matthew Ulman, Kenneth T Kotz, Shannon L Stott, Shyamala Maheswaran, Daniel A Haber, Mehmet TonerAbstract:Microfluidic systems for affinity-based Cell isolation have emerged as a promising approach for the isolation of specific Cells from complex matrices (i.e., circulating tumor Cells in whole blood). However, these technologies remain limited by the lack of reliable methods for the innocuous recovery of surface Captured Cells. Here, we present a biofunctional sacrificial hydrogel coating for microfluidic chips that enables the highly efficient release of isolated Cells (99% ± 1%) following gel dissolution. This covalently cross-linked alginate biopolymer system is stable in a wide variety of physiologic solutions (including EDTA treated whole blood) and may be rapidly degraded via backbone cleavage with alginate lyase. The Capture and release of EpCAM expressing cancer Cells using this approach was found to have no significant effect on Cell viability or proliferative potential, and recovered Cells were demonstrated to be compatible with downstream immunostaining and FISH analysis.
Brandon J Tefft - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle mediated Cell Capture enables rapid endothelialization of a novel bare metal stent
Tissue Engineering Part A, 2018Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, B. Newman, Adriana Harbuzariu, Tyra A Witt, Peter J Psaltis, David R Holmes, Rajiv GulatiAbstract:Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic Cell Capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial Cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled Cells to 2205 SS stents. In this study, ...
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magnetizable stent grafts enable endothelial Cell Capture
Journal of Magnetism and Magnetic Materials, 2017Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, Amir Lerman, Dan Dragomirdaescu, Gurdas Singh SandhuAbstract:Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled Cells, drugs, and other therapeutic agents. Endothelial Cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been Captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial Cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully Captured Cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial Cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully Captured and retained SPION-labeled endothelial Cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform Cell Capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.
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Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention
Journal of Visualized Experiments, 2015Co-Authors: S Uthamaraj, O Hlinomaz, Brandon J Tefft, Gurdas Singh Sandhu, D Dragomir-daescuAbstract:Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The feasibility of using magnetic forces to Capture and retain endothelial outgrowth Cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has been shown previously. But this technique requires the development of a mechanically functional stent from a magnetic and biocompatible material followed by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided design (CAD) and its design was further refined using finite element analysis (FEA). The final design of the stent exhibited a principal strain below the fracture limit of the material during mechanical crimping and expansion. One hundred stents were manufactured and a subset of them was used for mechanical testing, retained magnetic field measurements, in-vitro Cell Capture studies, and in-vivo implantation studies. Ten stents were tested for deployment to verify if they sustained crimping and expansion cycle without failure. Another 10 stents were magnetized using a strong neodymium magnet and their retained magnetic field was measured. The stents showed that the retained magnetism was sufficient to Capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC Capture and retention was verified in large animal models by implanting 1 magnetized stent and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were explanted after 7 days and analyzed histologically. The weakly magnetic stents developed in this study were capable of attracting and retaining SPION-labeled endothelial Cells which can promote rapid healing.
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Design of a magnetic stent that enables rapid endothelial Cell Capture
Catheterization and Cardiovascular Interventions, 2014Co-Authors: Uthamaraj S., Tefft B.J., Gurdas Singh Sandhu, Brandon J Tefft, R D Simari, D R Holmes Jr, O Hlinomaz, M Klabusay, J J Harburn, S Uthamaraj, Dragomir-Daescu D., Sandhu G.S., Simari R.D., Holmes Jr D.R., Hlinomaz O., Klabusay M., Harburn J.J., Newman B., B. Newman, D Dragomir-daescuAbstract:Background: Both bare metal stents (BMS) and drug eluting stents (DES) provide benefit to patients with coronary heart disease (CHD), but they are not without drawbacks. BMS made of materials such as 316L stainless steel, cobalt chromium, and platinum chromium heal rapidly but are prone to late stage restenosis due to neointimal hyperplasia. DES mitigate restenosis but require long-term anti-platelet therapy and are prone to late stage thrombosis. Rapid stent endothelialization could potentially eliminate the need for anti-platelet therapy by making the stent blood compatible, but achieving rapid endothelialization has proved to be challenging. One approach is to seed self-expanding stents prior to implantation; however it is unclear if Cells will be retained following restoration of blood flow. Another approach is to Capture circulating endothelial progenitor Cells by coating the stents with antibodies or ligands; however, this approach suffers from non-specific and limited Cell Capture from circulating blood. A promising strategy is to directly deliver and Capture endothelial Cells to the stent after implantation. This strategy requires means to first Capture endothelial Cells and then to retain those Cells following restoration of blood flow. Research has shown that endothelial Cells labeled with magnetic particles can be Captured and retained by a magnetic stent and could potentially migrate and proliferate to subsequently form an endothelial monolayer. Most magnetic materials are unsuitable for stent fabrication since they are brittle, soft, and/or non-biocompatible. From a survey of materials, we identified the 2205 duplex stainless steel - UNS S31803/S32205 - (2205 SS) for its desirable mechanical properties, similarity to 316L stainless steel, and weak ferromagnetic properties. In the present study, we employed numerical methods to validate the design of a 2205 SS stent and we employed mechanical testing to verify the stent's ability to withstand the plastic deformation experienced during crimping and expansion. Finally, we studied the magnetic properties of the 2205 SS stent and demonstrated in vitro Cell Capture. Methods: Simple stent geometry with Z-struts connected peak-topeak with cross struts was designed for a 3 mm nominal diameter stent using computer aided design (CAD) software (SolidWorks, 2009, Dassault systems, Inc.). The CAD geometry was imported into finite element analysis (FEA) software (Abaqus 6.9-ef, Dassault systems, Inc.). A complete crimping and expansion process was simulated and the simulated strain distribution was analyzed for yield behavior. The design was iteratively modified so that the strain stayed within the 2205 SS fracture limit of 30%. Ten stents were laser cut from 2205 SS using the final design and subsequently electropolished. The manufactured stents were crimped onto a trifold balloon, expanded to 3 mm, and microscopically examined for signs of failure. The stents were also magnetized either axially or diametrically using a neodymium magnet. The retained magnetic field was mapped at different sections using a magnetic probe. Finally, in vitro Cell Capture studies were conducted. Porcine endothelial outgrowth Cells (EOCs) were derived from peripheral blood and labeled with super paramagnetic iron oxide nanoparticles (SPIONs). The Cells were also stained with a red fluorescent die (CM-DiI, Molecular Probes, Eugene, OR) for imaging. Magnetized stents were introduced into a suspension of SPION-labeled EOCs and imaged using a fluorescence microscope. Results: FEA of the final stent design revealed that during crimping and expansion the principal strain never exceeded 30% (Figure 1). The iterative design modifications at the peak strut segments allowed us to meet our design requirement of keeping the strain under 30% in all regions of the stent. For verification, crimped and expanded stents were examined under a microscope for cracks and fractures. The stent struts did not show any fracture and the inspection showed acceptably uniform stent expansion (Figure 2). Two different magnetization orientations proved to magnetize the stent struts differently. In the straight segments, axially magnetized stents showed magnetic fields in the range of 50-300 mG above background, while diametrically magnetized stents measured in the range of 50-600 mG above background. In the peak strut segments of both axially and diametrically magnetized stents the magnetic field was in the range of 100-800 mG above background (Figure 3). The magnetic poles were established at the peak strut segments of the stent except for where the inter-strut connections were present (see for example Figure 3b axially magnetized stent segment indices 3 and 7). When magnetized stents were exposed to SPION-labeled EOCs, the Cells were pulled to the stent and Captured on the surface. As predicted by the magnetization measurements, axially magnetized stents showed higher Cell attraction to the peak strut segments while the diametrically magnetized stents showed more even coverage with Cells (Figure 4). Conclusion: Rapid endothelialization of a vascular stent can be achieved by targeted Cell delivery using magnetized stents. Weakly ferromagnetic stents made of 2205 SS showed promise for the fabrication of a BMS that can be used to attract SPION labeled EOCs for rapid endothelialization. A comprehensive FEA analysis enabled the successful design and manufacturing of balloon-deployable stents. Different orientations of magnetization led to pronounced Cell attraction to different regions of the stents based on the strength of the retained magnetic field. Capturing and retaining EOCs on the stent immediately after implantation could enable rapid endothelialization and reduce the need for anti-platelet therapy. (Figure Presented).
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Magnetizable Duplex Steel Stents Enable Endothelial Cell Capture
IEEE Transactions on Magnetics, 2013Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, M Klabusay, R D Simari, D Dragomir-daescu, David R Holmes, Janelle Y. Gooden, Gurpreet S. SandhuAbstract:Emerging medical nanotechnology applications often utilize magnetic forces to guide the movement of superparamagnetic particle linked Cells and drugs in order to achieve a therapeutic effect. Superparamagnetic particle labeled endothelial Cells have previously been Captured on the surface of prototype nickel-plated stents in proof of concept studies. Facilitated endothelialization may help improve the healing of stented arteries and reduce the risk of stent thrombosis and restenosis. Extensive evaluation of candidate materials led to the development of a magnetizable 2205 duplex stainless steel stent. Magnetic field strengths of approximately 630 mG were induced within these stents by holding them in close proximity to a 0.7 T rare earth magnet. The magnetic field strength was reliably maintained over several days, but was partially reduced upon mild mechanical shock or plastic deformation. Mechanical testing demonstrated that stents could withstand crimping and expansion necessary for vascular implantation; however, magnetic field strength was significantly reduced. When placed in an endothelial Cell suspension of 1×106 Cells/mL, magnetized stents Captured approximately 310 Cells/mm2 compared to approximately 35 Cells/mm2 for non-magnetized control stents. These data provide quantitative support to the observation that low level magnetization of stents may be adequate to attract labeled, autologous, blood-derived endothelial outgrowth Cells following stent placement. This, in turn, may lead to more rapid and complete healing of stented arteries with a concomitant improvement in stent performance.
S Uthamaraj - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle mediated Cell Capture enables rapid endothelialization of a novel bare metal stent
Tissue Engineering Part A, 2018Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, B. Newman, Adriana Harbuzariu, Tyra A Witt, Peter J Psaltis, David R Holmes, Rajiv GulatiAbstract:Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic Cell Capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial Cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled Cells to 2205 SS stents. In this study, ...
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magnetizable stent grafts enable endothelial Cell Capture
Journal of Magnetism and Magnetic Materials, 2017Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, Amir Lerman, Dan Dragomirdaescu, Gurdas Singh SandhuAbstract:Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled Cells, drugs, and other therapeutic agents. Endothelial Cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been Captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial Cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully Captured Cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial Cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully Captured and retained SPION-labeled endothelial Cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform Cell Capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.
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Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention
Journal of Visualized Experiments, 2015Co-Authors: S Uthamaraj, O Hlinomaz, Brandon J Tefft, Gurdas Singh Sandhu, D Dragomir-daescuAbstract:Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The feasibility of using magnetic forces to Capture and retain endothelial outgrowth Cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has been shown previously. But this technique requires the development of a mechanically functional stent from a magnetic and biocompatible material followed by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided design (CAD) and its design was further refined using finite element analysis (FEA). The final design of the stent exhibited a principal strain below the fracture limit of the material during mechanical crimping and expansion. One hundred stents were manufactured and a subset of them was used for mechanical testing, retained magnetic field measurements, in-vitro Cell Capture studies, and in-vivo implantation studies. Ten stents were tested for deployment to verify if they sustained crimping and expansion cycle without failure. Another 10 stents were magnetized using a strong neodymium magnet and their retained magnetic field was measured. The stents showed that the retained magnetism was sufficient to Capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC Capture and retention was verified in large animal models by implanting 1 magnetized stent and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were explanted after 7 days and analyzed histologically. The weakly magnetic stents developed in this study were capable of attracting and retaining SPION-labeled endothelial Cells which can promote rapid healing.
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Design of a magnetic stent that enables rapid endothelial Cell Capture
Catheterization and Cardiovascular Interventions, 2014Co-Authors: Uthamaraj S., Tefft B.J., Gurdas Singh Sandhu, Brandon J Tefft, R D Simari, D R Holmes Jr, O Hlinomaz, M Klabusay, J J Harburn, S Uthamaraj, Dragomir-Daescu D., Sandhu G.S., Simari R.D., Holmes Jr D.R., Hlinomaz O., Klabusay M., Harburn J.J., Newman B., B. Newman, D Dragomir-daescuAbstract:Background: Both bare metal stents (BMS) and drug eluting stents (DES) provide benefit to patients with coronary heart disease (CHD), but they are not without drawbacks. BMS made of materials such as 316L stainless steel, cobalt chromium, and platinum chromium heal rapidly but are prone to late stage restenosis due to neointimal hyperplasia. DES mitigate restenosis but require long-term anti-platelet therapy and are prone to late stage thrombosis. Rapid stent endothelialization could potentially eliminate the need for anti-platelet therapy by making the stent blood compatible, but achieving rapid endothelialization has proved to be challenging. One approach is to seed self-expanding stents prior to implantation; however it is unclear if Cells will be retained following restoration of blood flow. Another approach is to Capture circulating endothelial progenitor Cells by coating the stents with antibodies or ligands; however, this approach suffers from non-specific and limited Cell Capture from circulating blood. A promising strategy is to directly deliver and Capture endothelial Cells to the stent after implantation. This strategy requires means to first Capture endothelial Cells and then to retain those Cells following restoration of blood flow. Research has shown that endothelial Cells labeled with magnetic particles can be Captured and retained by a magnetic stent and could potentially migrate and proliferate to subsequently form an endothelial monolayer. Most magnetic materials are unsuitable for stent fabrication since they are brittle, soft, and/or non-biocompatible. From a survey of materials, we identified the 2205 duplex stainless steel - UNS S31803/S32205 - (2205 SS) for its desirable mechanical properties, similarity to 316L stainless steel, and weak ferromagnetic properties. In the present study, we employed numerical methods to validate the design of a 2205 SS stent and we employed mechanical testing to verify the stent's ability to withstand the plastic deformation experienced during crimping and expansion. Finally, we studied the magnetic properties of the 2205 SS stent and demonstrated in vitro Cell Capture. Methods: Simple stent geometry with Z-struts connected peak-topeak with cross struts was designed for a 3 mm nominal diameter stent using computer aided design (CAD) software (SolidWorks, 2009, Dassault systems, Inc.). The CAD geometry was imported into finite element analysis (FEA) software (Abaqus 6.9-ef, Dassault systems, Inc.). A complete crimping and expansion process was simulated and the simulated strain distribution was analyzed for yield behavior. The design was iteratively modified so that the strain stayed within the 2205 SS fracture limit of 30%. Ten stents were laser cut from 2205 SS using the final design and subsequently electropolished. The manufactured stents were crimped onto a trifold balloon, expanded to 3 mm, and microscopically examined for signs of failure. The stents were also magnetized either axially or diametrically using a neodymium magnet. The retained magnetic field was mapped at different sections using a magnetic probe. Finally, in vitro Cell Capture studies were conducted. Porcine endothelial outgrowth Cells (EOCs) were derived from peripheral blood and labeled with super paramagnetic iron oxide nanoparticles (SPIONs). The Cells were also stained with a red fluorescent die (CM-DiI, Molecular Probes, Eugene, OR) for imaging. Magnetized stents were introduced into a suspension of SPION-labeled EOCs and imaged using a fluorescence microscope. Results: FEA of the final stent design revealed that during crimping and expansion the principal strain never exceeded 30% (Figure 1). The iterative design modifications at the peak strut segments allowed us to meet our design requirement of keeping the strain under 30% in all regions of the stent. For verification, crimped and expanded stents were examined under a microscope for cracks and fractures. The stent struts did not show any fracture and the inspection showed acceptably uniform stent expansion (Figure 2). Two different magnetization orientations proved to magnetize the stent struts differently. In the straight segments, axially magnetized stents showed magnetic fields in the range of 50-300 mG above background, while diametrically magnetized stents measured in the range of 50-600 mG above background. In the peak strut segments of both axially and diametrically magnetized stents the magnetic field was in the range of 100-800 mG above background (Figure 3). The magnetic poles were established at the peak strut segments of the stent except for where the inter-strut connections were present (see for example Figure 3b axially magnetized stent segment indices 3 and 7). When magnetized stents were exposed to SPION-labeled EOCs, the Cells were pulled to the stent and Captured on the surface. As predicted by the magnetization measurements, axially magnetized stents showed higher Cell attraction to the peak strut segments while the diametrically magnetized stents showed more even coverage with Cells (Figure 4). Conclusion: Rapid endothelialization of a vascular stent can be achieved by targeted Cell delivery using magnetized stents. Weakly ferromagnetic stents made of 2205 SS showed promise for the fabrication of a BMS that can be used to attract SPION labeled EOCs for rapid endothelialization. A comprehensive FEA analysis enabled the successful design and manufacturing of balloon-deployable stents. Different orientations of magnetization led to pronounced Cell attraction to different regions of the stents based on the strength of the retained magnetic field. Capturing and retaining EOCs on the stent immediately after implantation could enable rapid endothelialization and reduce the need for anti-platelet therapy. (Figure Presented).
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Magnetizable Duplex Steel Stents Enable Endothelial Cell Capture
IEEE Transactions on Magnetics, 2013Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, M Klabusay, R D Simari, D Dragomir-daescu, David R Holmes, Janelle Y. Gooden, Gurpreet S. SandhuAbstract:Emerging medical nanotechnology applications often utilize magnetic forces to guide the movement of superparamagnetic particle linked Cells and drugs in order to achieve a therapeutic effect. Superparamagnetic particle labeled endothelial Cells have previously been Captured on the surface of prototype nickel-plated stents in proof of concept studies. Facilitated endothelialization may help improve the healing of stented arteries and reduce the risk of stent thrombosis and restenosis. Extensive evaluation of candidate materials led to the development of a magnetizable 2205 duplex stainless steel stent. Magnetic field strengths of approximately 630 mG were induced within these stents by holding them in close proximity to a 0.7 T rare earth magnet. The magnetic field strength was reliably maintained over several days, but was partially reduced upon mild mechanical shock or plastic deformation. Mechanical testing demonstrated that stents could withstand crimping and expansion necessary for vascular implantation; however, magnetic field strength was significantly reduced. When placed in an endothelial Cell suspension of 1×106 Cells/mL, magnetized stents Captured approximately 310 Cells/mm2 compared to approximately 35 Cells/mm2 for non-magnetized control stents. These data provide quantitative support to the observation that low level magnetization of stents may be adequate to attract labeled, autologous, blood-derived endothelial outgrowth Cells following stent placement. This, in turn, may lead to more rapid and complete healing of stented arteries with a concomitant improvement in stent performance.
O Hlinomaz - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle mediated Cell Capture enables rapid endothelialization of a novel bare metal stent
Tissue Engineering Part A, 2018Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, B. Newman, Adriana Harbuzariu, Tyra A Witt, Peter J Psaltis, David R Holmes, Rajiv GulatiAbstract:Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic Cell Capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial Cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled Cells to 2205 SS stents. In this study, ...
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magnetizable stent grafts enable endothelial Cell Capture
Journal of Magnetism and Magnetic Materials, 2017Co-Authors: Brandon J Tefft, S Uthamaraj, J J Harburn, O Hlinomaz, Amir Lerman, Dan Dragomirdaescu, Gurdas Singh SandhuAbstract:Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled Cells, drugs, and other therapeutic agents. Endothelial Cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been Captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial Cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully Captured Cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial Cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully Captured and retained SPION-labeled endothelial Cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform Cell Capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.
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Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention
Journal of Visualized Experiments, 2015Co-Authors: S Uthamaraj, O Hlinomaz, Brandon J Tefft, Gurdas Singh Sandhu, D Dragomir-daescuAbstract:Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The feasibility of using magnetic forces to Capture and retain endothelial outgrowth Cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has been shown previously. But this technique requires the development of a mechanically functional stent from a magnetic and biocompatible material followed by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided design (CAD) and its design was further refined using finite element analysis (FEA). The final design of the stent exhibited a principal strain below the fracture limit of the material during mechanical crimping and expansion. One hundred stents were manufactured and a subset of them was used for mechanical testing, retained magnetic field measurements, in-vitro Cell Capture studies, and in-vivo implantation studies. Ten stents were tested for deployment to verify if they sustained crimping and expansion cycle without failure. Another 10 stents were magnetized using a strong neodymium magnet and their retained magnetic field was measured. The stents showed that the retained magnetism was sufficient to Capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC Capture and retention was verified in large animal models by implanting 1 magnetized stent and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were explanted after 7 days and analyzed histologically. The weakly magnetic stents developed in this study were capable of attracting and retaining SPION-labeled endothelial Cells which can promote rapid healing.
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Design of a magnetic stent that enables rapid endothelial Cell Capture
Catheterization and Cardiovascular Interventions, 2014Co-Authors: Uthamaraj S., Tefft B.J., Gurdas Singh Sandhu, Brandon J Tefft, R D Simari, D R Holmes Jr, O Hlinomaz, M Klabusay, J J Harburn, S Uthamaraj, Dragomir-Daescu D., Sandhu G.S., Simari R.D., Holmes Jr D.R., Hlinomaz O., Klabusay M., Harburn J.J., Newman B., B. Newman, D Dragomir-daescuAbstract:Background: Both bare metal stents (BMS) and drug eluting stents (DES) provide benefit to patients with coronary heart disease (CHD), but they are not without drawbacks. BMS made of materials such as 316L stainless steel, cobalt chromium, and platinum chromium heal rapidly but are prone to late stage restenosis due to neointimal hyperplasia. DES mitigate restenosis but require long-term anti-platelet therapy and are prone to late stage thrombosis. Rapid stent endothelialization could potentially eliminate the need for anti-platelet therapy by making the stent blood compatible, but achieving rapid endothelialization has proved to be challenging. One approach is to seed self-expanding stents prior to implantation; however it is unclear if Cells will be retained following restoration of blood flow. Another approach is to Capture circulating endothelial progenitor Cells by coating the stents with antibodies or ligands; however, this approach suffers from non-specific and limited Cell Capture from circulating blood. A promising strategy is to directly deliver and Capture endothelial Cells to the stent after implantation. This strategy requires means to first Capture endothelial Cells and then to retain those Cells following restoration of blood flow. Research has shown that endothelial Cells labeled with magnetic particles can be Captured and retained by a magnetic stent and could potentially migrate and proliferate to subsequently form an endothelial monolayer. Most magnetic materials are unsuitable for stent fabrication since they are brittle, soft, and/or non-biocompatible. From a survey of materials, we identified the 2205 duplex stainless steel - UNS S31803/S32205 - (2205 SS) for its desirable mechanical properties, similarity to 316L stainless steel, and weak ferromagnetic properties. In the present study, we employed numerical methods to validate the design of a 2205 SS stent and we employed mechanical testing to verify the stent's ability to withstand the plastic deformation experienced during crimping and expansion. Finally, we studied the magnetic properties of the 2205 SS stent and demonstrated in vitro Cell Capture. Methods: Simple stent geometry with Z-struts connected peak-topeak with cross struts was designed for a 3 mm nominal diameter stent using computer aided design (CAD) software (SolidWorks, 2009, Dassault systems, Inc.). The CAD geometry was imported into finite element analysis (FEA) software (Abaqus 6.9-ef, Dassault systems, Inc.). A complete crimping and expansion process was simulated and the simulated strain distribution was analyzed for yield behavior. The design was iteratively modified so that the strain stayed within the 2205 SS fracture limit of 30%. Ten stents were laser cut from 2205 SS using the final design and subsequently electropolished. The manufactured stents were crimped onto a trifold balloon, expanded to 3 mm, and microscopically examined for signs of failure. The stents were also magnetized either axially or diametrically using a neodymium magnet. The retained magnetic field was mapped at different sections using a magnetic probe. Finally, in vitro Cell Capture studies were conducted. Porcine endothelial outgrowth Cells (EOCs) were derived from peripheral blood and labeled with super paramagnetic iron oxide nanoparticles (SPIONs). The Cells were also stained with a red fluorescent die (CM-DiI, Molecular Probes, Eugene, OR) for imaging. Magnetized stents were introduced into a suspension of SPION-labeled EOCs and imaged using a fluorescence microscope. Results: FEA of the final stent design revealed that during crimping and expansion the principal strain never exceeded 30% (Figure 1). The iterative design modifications at the peak strut segments allowed us to meet our design requirement of keeping the strain under 30% in all regions of the stent. For verification, crimped and expanded stents were examined under a microscope for cracks and fractures. The stent struts did not show any fracture and the inspection showed acceptably uniform stent expansion (Figure 2). Two different magnetization orientations proved to magnetize the stent struts differently. In the straight segments, axially magnetized stents showed magnetic fields in the range of 50-300 mG above background, while diametrically magnetized stents measured in the range of 50-600 mG above background. In the peak strut segments of both axially and diametrically magnetized stents the magnetic field was in the range of 100-800 mG above background (Figure 3). The magnetic poles were established at the peak strut segments of the stent except for where the inter-strut connections were present (see for example Figure 3b axially magnetized stent segment indices 3 and 7). When magnetized stents were exposed to SPION-labeled EOCs, the Cells were pulled to the stent and Captured on the surface. As predicted by the magnetization measurements, axially magnetized stents showed higher Cell attraction to the peak strut segments while the diametrically magnetized stents showed more even coverage with Cells (Figure 4). Conclusion: Rapid endothelialization of a vascular stent can be achieved by targeted Cell delivery using magnetized stents. Weakly ferromagnetic stents made of 2205 SS showed promise for the fabrication of a BMS that can be used to attract SPION labeled EOCs for rapid endothelialization. A comprehensive FEA analysis enabled the successful design and manufacturing of balloon-deployable stents. Different orientations of magnetization led to pronounced Cell attraction to different regions of the stents based on the strength of the retained magnetic field. Capturing and retaining EOCs on the stent immediately after implantation could enable rapid endothelialization and reduce the need for anti-platelet therapy. (Figure Presented).