Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Med Res ; 26(1): 121, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641963

RESUMO

BACKGROUND: Percutaneous coronary interventions (PCI) of bifurcation stenoses are both complex and challenging. Stenting strategies share that the stents' side cells must be carefully explored and appropriately prepared using balloons or stents. So far, stent manufacturers have not provided any information regarding side-branch expansion capacity of their stent platforms. AIMS: Given that drug-eluting stent (DES) information regarding their mechanical capacity of side-branch expansion is not available, we aimed to evaluate contemporary DES (Orsiro, BIOTRONIK AG; Xience Sierra, Abbott Vascular; Resolute Integrity, Medtronic; Promus Premier Select, Boston Scientific; Supraflex Cruz, Sahajan and Medical Technologies) by their side-branch expansion behavior using in vitro bench testing. METHODS: In this in vitro study, we analyzed five commercially available DES (diameter 3.0 mm), measuring their side-branch expansion following inflation of different high-pressure non-compliant (NC) balloons (balloon diameter: 2.00-4.00 mm), thereby revealing the morphological characteristics of their side-branch expansion capacities. RESULTS: We demonstrated that all tested contemporary DES platforms could withstand large single-cell deformations, up to 4.0 mm. As seen in our side-branch experiments, DES designs consisting of only two connectors between strut rings did not only result in huge cell areas, but also in larger cell diameters following side-branch expansion compared with DES designs using three or more connectors. Furthermore, the stent cell diameter attained was below the balloon diameter at normal pressure. CONCLUSIONS: We recommend that the expansion capacity of side-branches should be considered in stent selection for bifurcation interventions.

2.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199303

RESUMO

The main purpose of new stent technologies is to overcome unfavorable material-related incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and anti-thrombogenic properties. In this context, wettability is an important surface property, which has a major impact on the biological response of blood cells. However, the influence of local hemodynamic changes also influences blood cell activation. Therefore, we investigated biodegradable polymers with different wettability to identify possible aspects for a better prediction of blood compatibility. We applied shear rates of 100 s-1 and 1500 s-1 and assessed platelet and monocyte activation as well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of circulating platelets induced by collagen was assessed by light transmission aggregometry. Via live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity. Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to low shear rates of 100 s-1, activation of circulating platelets and monocytes as well as the formation of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however, blood compatibility cannot only be predicted by the concept of wettability. We assume that the mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the blood compatibility of a material, which makes extensive in vitro testing mandatory.


Assuntos
Plaquetas/citologia , Comunicação Celular/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Poliésteres/farmacologia , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Agregação Plaquetária/efeitos dos fármacos , Água , Molhabilidade
3.
BMC Mol Cell Biol ; 22(1): 32, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078283

RESUMO

BACKGROUND: Endothelial healing after deployment of cardiovascular devices is particularly important in the context of clinical outcome. It is therefore of great interest to develop tools for a precise prediction of endothelial growth after injury in the process of implant deployment. For experimental investigation of re-endothelialization in vitro cell migration assays are routinely used. However, semi-automatic analyses of live cell images are often based on gray value distributions and are as such limited by image quality and user dependence. The rise of deep learning algorithms offers promising opportunities for application in medical image analysis. Here, we present an intelligent cell detection (iCD) approach for comprehensive assay analysis to obtain essential characteristics on cell and population scale. RESULTS: In an in vitro wound healing assay, we compared conventional analysis methods with our iCD approach. Therefore we determined cell density and cell velocity on cell scale and the movement of the cell layer as well as the gap closure between two cell monolayers on population scale. Our data demonstrate that cell density analysis based on deep learning algorithms is superior to an adaptive threshold method regarding robustness against image distortion. In addition, results on cell scale obtained with iCD are in agreement with manually velocity detection, while conventional methods, such as Cell Image Velocimetry (CIV), underestimate cell velocity by a factor of 0.5. Further, we found that iCD analysis of the monolayer movement gave results just as well as manual freehand detection, while conventional methods again shows more frayed leading edge detection compared to manual detection. Analysis of monolayer edge protrusion by ICD also produced results, which are close to manual estimation with an relative error of 11.7%. In comparison, the conventional Canny method gave a relative error of 76.4%. CONCLUSION: The results of our experiments indicate that deep learning algorithms such as our iCD have the ability to outperform conventional methods in the field of wound healing analysis. The combined analysis on cell and population scale using iCD is very well suited for timesaving and high quality wound healing analysis enabling the research community to gain detailed understanding of endothelial movement.

4.
Biomed Mater ; 16(1): 015022, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33022660

RESUMO

An ongoing challenge in drug delivery systems for a variety of medical applications, including cardiovascular diseases, is the delivery of multiple drugs to address numerous phases of a treatment or healing process. Therefore, an extended dual drug delivery system (DDDS) based on our previously reported cardiac DDDS was generated. Here we use the polymer poly(L-lactide) (PLLA) as drug carrier with the cytostatic drug Paclitaxel (PTX) and the endothelial cell proliferation enhancing growth factor, human vascular endothelial growth factor (VEGF), to overcome typical in-stent restenosis complications. We succeeded in using one solution to generate two separate DDDS via spray coating (film) and electrospinning (nonwoven) with the same content of PTX and the same post processing for VEGF immobilisation. Both processes are suitable as coating techniques for implants. The contact angle analysis revealed differences between films and nonwovens. Whereas, the morphological analysis demonstrated nearly no changes occurred after immobilisation of both drugs. Glass transition temperatures (Tg ) and degree of crystallinity (χ) show only minor changes. The amount of immobilised VEGF on nonwovens was over 300% higher compared to the films. Also, the nonwovens revealed a much faster and over three times higher PTX release over 70 d compared to the films. The almost equal physical properties of nonwovens and films allow the comparison of both DDDS independently of their fabrication process. Both films and nonwovens have significantly increased in vitro cell viability for human umbilical vein endothelial cells (EA.hy926) with dual loaded PTX and VEGF compared to PTX-only loaded samples.

5.
Radiologe ; 60(Suppl 1): 70-79, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32926194

RESUMO

Three-dimensional (3D) imaging has been available for nearly four decades and is regarded as state of the art for visualization of anatomy and pathology and for procedure planning in many clinical fields. Together with 3D image reconstructions in the form of rendered virtual 3D models, it has helped to better perceive complex anatomic and pathologic relations, improved preprocedural measuring and sizing of implants, and nowadays enables even photorealistic quality. However, presentation on 2D displays limits the 3D experience. Novel 3D printing technologies can transfer virtual anatomic models into true 3D space and produce both patient-specific models and medical devices constructed by computer-aided design. Individualized anatomic models hold great potential for medical and patient education, research, device development and testing, procedure training, preoperative planning, and fabrication of individualized instruments and implants. Hand in hand with 3D imaging, medical 3D printing has started to revolutionize medicine in certain fields and new applications are developed and introduced regularly. The demand for medical 3D printing will likely continue to rise, as it is a promising tool for plastic preparation of medical interventions. However, there is ongoing debate on the appropriateness of medical 3D printing and further research on its efficiency is needed. As experts in 3D imaging, radiologists are not only capable of advising on adequate imaging parameters, but should also become adept in 3D printing to participate in on-site 3D printing facilities and randomized controlled trials on the topic, thus contributing to improving patient outcomes via personalized medicine through patient-specific preparation of medical interventions.


Assuntos
Imageamento Tridimensional , Modelos Anatômicos , Plásticos , Impressão Tridimensional , Humanos , Radiologistas , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Mech Behav Biomed Mater ; 91: 174-181, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30583263

RESUMO

Resorbable magnesium scaffolds are used for the treatment of atherosclerotic coronary vascular disease and furthermore, for vascular restoration therapy. Recently, the first-in-man clinical studies with Magmaris showed promising results regarding the target lesion failure as well as vasomotion properties after 12 and 24 month. The consistency of in vivo degraded magnesium alloys in a cardiovascular environment is qualitatively described in literature, but only little has been disclosed about the actual change in mechanical properties and the behavior of the magnesium alloy degradation products. In the present study, uncoated magnesium scaffolds 3.0 × 20 mm were implanted in coronary arteries of two healthy Goetinnger mini-swine. The scaffolds were explanted to evaluate the mechanical properties of the degraded magnesium scaffolds after 180 days in vivo. Ex vivo sample preparation and test conditions were adapted to a customized compression test setup which was developed to investigate the micro-scale scaffold fragments (width 225 ±â€¯75 µm, thickness 150 µm). As reference bare undegraded magnesium scaffold fragments were tested. Mechanical parameters relating to force as a function of displacement were determined for both sample groups. The undegraded samples showed no fracturing at the maximum applied force of 8 N, whereas the in vivo degraded test samples showed forces of 0.411 ±â€¯0.197 N at the first fracturing and a maximum force of 0.956 ±â€¯0.525 N. The deformation work, calculated as area beneath the force-displacement curve, of the in vivo degraded test samples was reduced by approximately 87-88% compared to the undegraded samples (5.20 mN mm and 40.79 mN mm, both at 7.5% deformation). The indication for a complete loss of structural integrity through a reduction of mechanical properties after a certain degradation time increases the chance to restore vascular function and physiological vasomotion in the stented vessel compartment.


Assuntos
Implantes Absorvíveis , Magnésio/química , Magnésio/metabolismo , Fenômenos Mecânicos , Animais , Vasos Coronários , Teste de Materiais , Suínos
7.
Biomed Tech (Berl) ; 64(3): 251-262, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-29933242

RESUMO

Bioresorbable scaffolds (BRS) promise to be the treatment of choice for stenosed coronary vessels. But higher thrombosis risk found in current clinical studies limits the expectations. Three hemodynamic metrics are introduced to evaluate the thrombosis risk of coronary stents/scaffolds using transient computational fluid dynamics (CFD). The principal phenomena are platelet activation and effective diffusion (platelet shear number, PSN), convective platelet transport (platelet convection number, PCN) and platelet aggregation (platelet aggregation number, PAN) were taken into consideration. In the present study, two different stent designs (thick-strut vs. thin-strut design) positioned in small- and medium-sized vessels (reference vessel diameter, RVD=2.25 mm vs. 2.70 mm) were analyzed. In both vessel models, the thick-strut design induced higher PSN, PCN and PAN values than the thin-strut design (thick-strut vs. thin-strut: PSN=2.92/2.19 and 0.54/0.30; PCN=3.14/1.15 and 2.08/0.43; PAN: 14.76/8.19 and 20.03/10.18 for RVD=2.25 mm and 2.70 mm). PSN and PCN are increased by the reduction of the vessel size (PSN: RVD=2.25 mm vs. 2.70 mm=5.41 and 7.30; PCN: RVD=2.25 mm vs. 2.70 mm=1.51 and 2.67 for thick-strut and thin-strut designs). The results suggest that bulky stents implanted in small caliber vessels may substantially increase the thrombosis risk. Moreover, sensitivity analyses imply that PSN is mostly influenced by vessel size (lesion-related factor), whereas PCN and PAN sensitively respond to strut-thickness (device-related factor).


Assuntos
Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Implantes Absorvíveis , Doença da Artéria Coronariana/fisiopatologia , Hemodinâmica , Humanos , Stents , Trombose , Resultado do Tratamento
8.
Klin Monbl Augenheilkd ; 235(12): 1360-1365, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30566996

RESUMO

PURPOSE: Evaluation of the long-term efficiency of MIGS implants is still challenging, due to the lack of standardized clinical studies of stand-alone procedures. Moreover, the different mechanisms of the various glaucoma drainage devices are not adequately considered. The current study focusses on the development of a method for oculopression to evaluate the efficiency of glaucoma drainage devices. METHODS: Explanted porcine eyes were subjected to pressure or weight load using three oculopressors with different modi operandi. The time-dependent intraocular pressure was measured using an anterior chamber maintainer. The Honan Balloon exerts variable pressure onto the eye via an air bellows, whereas the Taylor oculopressor applies a defined weight loading on the eye. A novel oculopressor with a weight loading of 60 g was developed and manufactured by means of 3-D-printing. RESULTS: The intraocular pressure changes observed during the experiments were similar for all tested oculopression devices, varying only in the absolute pressure values. The Honan Balloon was not suitable for the intended purpose, due to poor standardisation of the applied pressure. Oculopression using a defined weight appeared more suitable. The Taylor oculopressor, however, created intraocular pressure values of up to 203.3 ± 38.4 mmHg, which precludes its use with glaucoma patients. On the basis of these data, the new oculopression device was used in a preliminary trial with healthy human subjects, thereby preparing its use in a clinical trial. CONCLUSIONS: Oculopression represents a potentially suitable tool to analyse the efficiency of glaucoma drainage devices. Commercially available oculopression devices are not directly applicable for this task. Difficult handling, high intraocular pressure, and lack of standardisation complicate the use for glaucoma patients. These difficulties were overcome with the newly designed oculopressor that facilitates a well defined increase in intraocular pressure. The device is currently being used in a clinical study to evaluate the efficiency of MIGS implants.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Animais , Câmara Anterior , Drenagem , Humanos , Pressão Intraocular , Suínos
9.
Biosci Rep ; 38(4)2018 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-30061178

RESUMO

To prevent implant failure due to fibrosis is a major objective in glaucoma research. The present study investigated the antifibrotic effects of paclitaxel (PTX), caffeic acid phenethyl ester (CAPE), and pirfenidone (PFD) coated microstent test specimens in a rat model. Test specimens based on a biodegradable blend of poly(4-hydroxybutyrate) biopolymer and atactic poly(3-hydroxybutyrate) (at.P(3HB)) were manufactured, equipped with local drug delivery (LDD) coatings, and implanted in the subcutaneous white fat depot. Postoperatively, test specimens were explanted and analyzed for residual drug content. Fat depots including the test specimens were histologically analyzed. In vitro drug release studies revealed an initial burst for LDD devices. In vivo, slow drug release of PTX was found, whereas it already completed 1 week postoperatively for CAPE and PFD LDD devices. Histological examinations revealed a massive cell infiltration in the periphery of the test specimens. Compact fibrotic capsules around the LDD devices were detectable at 4-36 weeks and least pronounced around PFD-coated specimens. Capsules stained positive for extracellular matrix (ECM) components. The presented model offers possibilities to investigate release kinetics and the antifibrotic potential of drugs in vivo as well as the identification of more effective agents for a novel generation of drug-eluting glaucoma microstents.


Assuntos
Ácidos Cafeicos/administração & dosagem , Sistemas de Liberação de Medicamentos/instrumentação , Stents Farmacológicos , Paclitaxel/administração & dosagem , Álcool Feniletílico/análogos & derivados , Piridonas/administração & dosagem , Animais , Ácidos Cafeicos/farmacocinética , Ácidos Cafeicos/uso terapêutico , Fibrose , Glaucoma/terapia , Masculino , Paclitaxel/farmacocinética , Paclitaxel/uso terapêutico , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacocinética , Álcool Feniletílico/uso terapêutico , Piridonas/farmacocinética , Piridonas/uso terapêutico , Ratos , Ratos Wistar
10.
Drug Deliv Transl Res ; 8(3): 719-728, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29532357

RESUMO

The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS3). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Proteínas Imobilizadas/administração & dosagem , Paclitaxel/administração & dosagem , Polímeros/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Antineoplásicos Fitogênicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Células Endoteliais/efeitos dos fármacos , Fluoresceínas/administração & dosagem , Fluoresceínas/química , Humanos , Proteínas Imobilizadas/química , Paclitaxel/química , Polímeros/química , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/química
11.
Eur J Med Res ; 23(1): 2, 2018 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310720

RESUMO

BACKGROUND: Drug-eluting stents (DES) compared to bare metal stents (BMS) have shown superior clinical performance, but are considered less suitable in complex cases. Most studies do not distinguish between DES and BMS with respect to their mechanical performance. The objective was to obtain mechanical parameters for direct comparison of BMS and DES. METHODS: In vitro bench tests evaluated crimped stent profiles, crossability in stenosis models, elastic recoil, bending stiffness (crimped and expanded), and scaffolding properties. The study included five pairs of BMS and DES each with the same stent platforms (all n = 5; PRO-Kinetic Energy, Orsiro: BIOTRONIK AG, Bülach, Switzerland; MULTI-LINK 8, XIENCE Xpedition: Abbott Vascular, Temecula, CA; REBEL Monorail, Promus PREMIER, Boston Scientific, Marlborough, MA; Integrity, Resolute Integrity, Medtronic, Minneapolis, MN; Kaname, Ultimaster: Terumo Corporation, Tokyo, Japan). Statistical analysis used pooled variance t tests for pairwise comparison of BMS with DES. RESULTS: Crimped profiles in BMS groups ranged from 0.97 ± 0.01 mm (PRO-Kinetic Energy) to 1.13 ± 0.01 mm (Kaname) and in DES groups from 1.02 ± 0.01 mm (Orsiro) to 1.13 ± 0.01 mm (Ultimaster). Crossability was best for low profile stent systems. Elastic recoil ranged from 4.07 ± 0.22% (Orsiro) to 5.87 ± 0.54% (REBEL Monorail) including both BMS and DES. The bending stiffness of crimped and expanded stents showed no systematic differences between BMS and DES neither did the scaffolding. CONCLUSIONS: Based on in vitro measurements BMS appear superior to DES in some aspects of mechanical performance, yet the differences are small and not class uniform. The data provide assistance in selecting the optimal system for treatment and assessment of new generations of bioresorbable scaffolds. TRIAL REGISTRATION: not applicable.


Assuntos
Stents Farmacológicos/normas , Stents Metálicos Autoexpansíveis/normas , Stents Farmacológicos/efeitos adversos , Fenômenos Mecânicos , Stents Metálicos Autoexpansíveis/efeitos adversos
12.
Biomed Microdevices ; 19(4): 78, 2017 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-28844120

RESUMO

Within this paper we analyzed the technical feasibility of a novel microstent for glaucoma therapy. For lowering of intraocular pressure, the flexible polyurethane (PUR) implant is designed to drain aqueous humour from the anterior chamber of the eye into subconjunctival, or alternatively suprachoroidal, space. The microstent includes a biodegradable, flow resisting polymer membrane serving as temporary flow resistance for the prevention of early postoperative hypotony. A biodegradable local drug delivery (LDD)-device was designed to prevent fibrous encapsulation. Biodegradable components were made of flexible, nonwoven membranes of Poly(4-hydroxybutyrate) (P(4HB)). Polymer samples and microstent prototypes were manufactured by means of dip coating, electrospinning and femtosecond-laser micromachining and characterized in vitro with regard to structural and fluid mechanical properties, degradation behavior and drug release. Bending stiffness of PUR-tubing (62.53 ± 7.57 mN mm2) is comparable to conventional glaucoma drainage devices in a tube-plate design. Microstent prototypes yield a flow resistance of 2.4 ± 0.6 mmHg/µl min-1 which is close to the aspired value corresponding to physiological pressure (15 mmHg) and aqueous humour flow (2 µl min-1) conditions inside the eye. Degradation of electrospun P(4HB) specimens was found to be almost completely finished after six months in vitro. Within this time frame, flow capacity of the microstent increases, which is beneficial to compensate potentially increasing flow resistance of fibrous tissue in vivo. Fast drug release of the LDD-device was found. One microstent prototype was implanted into a porcine eye ex vivo. Future preclinical studies will allow further information about Microstent performance.


Assuntos
Implantes Absorvíveis , Implantes de Medicamento , Glaucoma/terapia , Teste de Materiais , Poliésteres , Stents , Animais , Implantes de Medicamento/química , Implantes de Medicamento/farmacologia , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Humanos , Poliésteres/química , Poliésteres/farmacologia , Suínos
13.
PLoS One ; 12(2): e0172592, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28231275

RESUMO

In glaucoma surgery, fibrotic processes occur, leading to impairment of liquid outflow. Activated fibroblasts are responsible for postoperative scarring. The transforming growth factor-ß (TGF-ß) pathway plays a key role in fibroblast function, differentiation and proliferation. The aim of this study was the characterization of the fibrotic potential of two subtypes of primary human ocular fibroblasts and the attempt to inhibit fibrotic processes specifically, without impairing cell viability. For fibrosis inhibition we focused on the small molecule pirfenidone, which has been shown to prevent pulmonary fibrosis by the decrease of the expression of TGF-ß1, TGF-ß2 and TGF-ß3 cytokines. For in vitro examinations, isolated human primary fibroblasts from Tenon capsule and human intraconal orbital fat tissues were used. These fibroblast subpopulations were analyzed in terms of the expression of matrix components responsible for postoperative scarring. We concentrated on the expression of collagen I, III, VI and fibronectin. Additionally, we analyzed the expression of α-smooth muscle actin, which serves as a marker for fibrosis and indicates transformation of fibroblasts into myofibroblasts. Gene expression was analyzed by rtPCR and synthesized proteins were examined by immunofluorescence and Western blot methods. Proliferation of fibroblasts under different culture conditions was assessed using BrdU assay. TGF-ß1 induced a significant increase of cell proliferation in both cell types. Also the expression of some fibrotic markers was elevated. In contrast, pirfenidone decreased cell proliferation and matrix synthesis in both fibroblast subpopulations. Pirfenidone slightly attenuated TGF-ß1 induced expression of fibronectin and α-smooth muscle actin in fibroblast cultures, without impairing cell viability. To summarize, manipulation of the TGF-ß signaling pathway by pirfenidone represents a specific antifibrotic approach with no toxic side effects in two human orbital fibroblast subtypes. We presume that pirfenidone is a promising candidate for the treatment of fibrosis following glaucoma surgery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Piridonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/antagonistas & inibidores , Actinas/análise , Actinas/genética , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibronectinas/análise , Fibronectinas/genética , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fator de Crescimento Transformador beta/metabolismo
14.
Biomed Tech (Berl) ; 62(4): 349-355, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28076296

RESUMO

Embolic protection devices were developed to reduce the risk of stroke during carotid artery stenting. The aim of this study was to test the capture efficiency of five embolic protection devices under reproducible in vitro conditions. The setup consisted of silicone tubes representing the vessel modeling round and oval cross sections. Spherical polystyrene particles (150 µm, COOH-coating) were used to simulate the plaque. The particles were inserted in a clean water circuit and either captured by the device or collected in a glass filter. The missed particles were counted by laser obscuration as a measure of device leakage. The systems Angioguard RX, RX Accunet, FiberNet, FilterWire EZ and EmboshieldNAV were analyzed. At the round cross section, FilterWire EZ demonstrated the highest capture efficiency (0% of missed particles) and RX Accunet the lowest, at 34%. The amount of leaked particles increased to 22% for FilterWire EZ and 89% for Angioguard RX during the test with the oval cross profile.


Assuntos
Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/fisiopatologia , Dispositivos de Proteção Embólica , Stents/normas , Acidente Vascular Cerebral/fisiopatologia , Humanos , Resultado do Tratamento
15.
Cardiovasc Revasc Med ; 17(6): 375-83, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27266902

RESUMO

BACKGROUND/PURPOSE: Biodegradable polymers are the main materials for coronary scaffolds. Magnesium has been investigated as a potential alternative and was successfully tested in human clinical trials. However, it is still challenging to achieve mechanical parameters comparative to permanent bare metal (BMS) and drug-eluting stents (DES). As such, in vitro tests are required to assess mechanical parameters correlated to the safety and efficacy of the device. METHODS/MATERIALS: In vitro bench tests evaluate scaffold profiles, length, deliverability, expansion behavior including acute elastic and time-dependent recoil, bending stiffness and radial strength. The Absorb GT1 (Abbott Vascular, Temecula, CA), DESolve (Elixir Medical Corporation, Sunnyvale, CA) and the Magmaris (BIOTRONIK AG, Bülach, Switzerland) that was previously tested in the BIOSOLVE II study, were tested. RESULTS: Crimped profiles were 1.38±0.01mm (Absorb GT1), 1.39±0.01mm (DESolve) and 1.44±0.00mm (Magmaris) enabling 6F compatibility. Trackability was measured depending on stiffness and force transmission (pushability). Acute elastic recoil was measured at free expansion and within a mock vessel, respectively, yielding results of 5.86±0.76 and 5.22±0.38% (Absorb), 7.85±3.45 and 9.42±0.21% (DESolve) and 5.57±0.72 and 4.94±0.31% (Magmaris). Time-dependent recoil (after 1h) was observed for the Absorb and DESolve scaffolds but not for the Magmaris. The self-correcting wall apposition behavior of the DESolve did not prevent time-dependent recoil under vessel loading. CONCLUSIONS: The results of the suggested test methods allow assessment of technical feasibility based on objective mechanical data and highlight the main differences between polymeric and metallic bioresorbable scaffolds.


Assuntos
Implantes Absorvíveis , Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Metais/química , Polímeros/química , Stents , Tecidos Suporte , Força Compressiva , Doença da Artéria Coronariana/diagnóstico por imagem , Elasticidade , Análise de Falha de Equipamento , Humanos , Teste de Materiais , Pressão , Desenho de Prótese , Falha de Prótese , Resistência à Tração , Fatores de Tempo
16.
Eur J Pharm Biopharm ; 96: 322-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26318979

RESUMO

Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83%±9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuent© Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.


Assuntos
Absorção Fisiológica , Inibidores da Angiogênese/metabolismo , Angioplastia Coronária com Balão/instrumentação , Artérias Carótidas/metabolismo , Sistemas de Liberação de Medicamentos , Paclitaxel/metabolismo , Matadouros , Adesividade , Adsorção , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/análise , Inibidores da Angiogênese/química , Animais , Artérias Carótidas/química , Meios de Contraste/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Técnicas In Vitro , Iohexol/análogos & derivados , Iohexol/química , Paclitaxel/administração & dosagem , Paclitaxel/análise , Paclitaxel/química , Perfusão , Povidona/química , Solventes/química , Propriedades de Superfície , Sus scrofa
17.
Transl Vis Sci Technol ; 4(3): 14, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26175960

RESUMO

PURPOSE: A novel glaucoma drainage device (GDD) with local drug delivery (LDD) system was created and characterized for safety and effectiveness after implantation into the suprachoroidal space (SCS) of rabbit eyes. METHODS: Thin films of two different polymers, Poly(3-hydroxybutyrate) (P(3HB)) and Poly(4-hydroxybutyrate) (P(4HB)), containing the drugs mitomycin C (MitC) or paclitaxel (PTX) were attached to silicone-tubes to create LDD devices. The release kinetics of these drugs were explored in vitro using high performance liquid chromatography (HPLC). Twenty-four New Zealand white rabbits, randomly divided into eight groups, were implanted with different kinds of microstents into SCS. The intraocular pressure (IOP) was monitored noninvasively. After 6 weeks, rabbits were sacrificed and enucleated eyes were used for anterior segment optical coherence tomography (OCT), micro magnetic resonance imaging (MRI), and histology. RESULTS: In vitro, faster drug release from both polymers was observed for MitC compared to PTX. Comparing polymers, the release from P(3HB) matrix was slower for both drugs. MRI and OCT showed all implants maintained a proper location. An effective IOP reduction was observed for up to 6 weeks in eyes with microstents combined with a drug-releasing LDD system. Overall, the surrounding tissue revealed mild-to-moderate inflammation. No pronounced fibrosis was observed in any of the groups. However, both drugs caused damage to the neighboring retina. CONCLUSIONS: The suprachoroidal microstent reduced IOP with mild inflammation in rabbit eyes. To avoid negative effects on the retina, it is necessary to identify novel drugs with less cytotoxicity. Future studies are needed to explore the fibrotic process over the long-term. TRANSLATIONAL RELEVANCE: The presented data serve as a proof of principle study for the concept of a suprachoroidal drug eluting microstent. Future device improvements will be focused on the design of LDD systems and the use of specific anti-inflammatory or antifibrotic agents with less cytotoxicity compared to MitC or PTX. Long-term animal studies using a reliable glaucoma model will be a further step towards clinical application and improvement of surgical glaucoma therapy.

18.
J Control Release ; 214: 1-11, 2015 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-26160303

RESUMO

In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro, a sustained LA release over a period of about 60days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26weeks. In vivo, LA was continuously released for 152days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release.


Assuntos
Túnica Conjuntiva , Glaucoma de Ângulo Aberto/tratamento farmacológico , Animais , Humor Aquoso/metabolismo , Materiais Biocompatíveis , Células Cultivadas , Preparações de Ação Retardada , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Olho/patologia , Glaucoma de Ângulo Aberto/patologia , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Injeções , Latanoprosta , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Polímeros , Pró-Fármacos/administração & dosagem , Prostaglandinas F Sintéticas/administração & dosagem , Prostaglandinas F Sintéticas/uso terapêutico , Coelhos
19.
Clin Biomech (Bristol, Avon) ; 30(7): 720-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25971847

RESUMO

BACKGROUND: Minimally invasive treatment of vertebral fractures is basically characterized by cement augmentation. Using the combination of a permanent implant plus cement, it is now conceivable that the amount of cement can be reduced and so this augmentation could be an attractive opportunity for use in traumatic fractures in young and middle-aged patients. The objective of this study was to determine the smallest volume of cement necessary to stabilize fractured vertebrae comparing the SpineJack system to the gold standard, balloon kyphoplasty. METHODS: 36 fresh frozen human cadaveric vertebral bodies (T11-L3) were utilized. After creating typical compression wedge fractures (AO A1.2.1), the vertebral bodies were reduced by SpineJack (n=18) or kyphoplasty (n=18) under preload (100N). Subsequently, different amounts of bone cement (10%, 16% or 30% of the vertebral body volume) were inserted. Finally, static and dynamic biomechanical tests were performed. FINDINGS: Following augmentation and fatigue tests, vertebrae treated with SpineJack did not show any significant loss of intraoperative height gain, in contrast to kyphoplasty. In the 10% and 16%-group the height restoration expressed as a percentage of the initial height was significantly increased with the SpineJack (>300%). Intraoperative SpineJack could preserve the maximum height gain (mean 1% height loss) better than kyphoplasty (mean 16% height loss). INTERPRETATION: In traumatic wedge fractures it is possible to reduce the amount of cement to 10% of the vertebral body volume when SpineJack is used without compromising the reposition height after reduction, in contrast to kyphoplasty that needs a 30% cement volume.


Assuntos
Cimentos Ósseos/uso terapêutico , Fraturas por Compressão/cirurgia , Cifoplastia/métodos , Próteses e Implantes , Fraturas da Coluna Vertebral/cirurgia , Idoso , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Coluna Vertebral/cirurgia
20.
J Mech Behav Biomed Mater ; 49: 23-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25974098

RESUMO

Drug eluting stents (DES) consist of platform, coating and drug. The platform often is a balloon-expandable bare metal stent made of the CoCr alloy L-605 or stainless steel 316 L. The function of the coating, typically a permanent polymer, is to hold and release the drug, which should improve therapeutic outcome. Before implantation, DES are compressed (crimped) to allow implantation in the human body. During implantation, DES are expanded by balloon inflation. Crimping, as well as expansion, causes high stresses and high strains locally in the DES struts, as well as in the polymer coating. These stresses and strains are important design criteria of DES. Usually, they are calculated numerically by finite element analysis (FEA), but experimental results for validation are hardly available. In this work, the X-ray diffraction (XRD) sin(2)ψ-technique is applied to in-situ determination of stress conditions of bare metal L-605 stents, and Poly-(L-lactide) (PLLA) coated stents. This provides a realistic characterization of the near-surface stress state and a validation option of the numerical FEA. XRD-results from terminal stent struts of the bare metal stent show an increasing compressive load stress in tangential direction with increasing stent expansion. These findings correlate with numerical FEA results. The PLLA-coating also bears increasing compressive load stress during expansion.


Assuntos
Cromo/química , Materiais Revestidos Biocompatíveis/química , Cobalto/química , Stents Farmacológicos , Teste de Materiais , Poliésteres/química , Estresse Mecânico , Análise de Elementos Finitos , Propriedades de Superfície , Difração de Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...