Etude et développement de dépôts d'allylamine assistés par plasma basse pression specifiques aux stents coronariens recouverts Les stents coronariens sont des dispositifs médicaux, généralement fabriqués en acier inoxydable 316L, utilisés pour traiter des maladies cardiovasculaires comme l'athérosclérose. Les stents recouverts ou à relargage contrôlé de médicaments sont des solutions prometteuses pour réduire les phénomènes de resténose. Ce travail a pour objectif le développement d'un procédé plasma basse pression capable de déposer une couche de polymère permettant de protéger la surface des stents contre l'agressivité du milieu physiologique. L'allylamine est choisie comme précurseur moléculaire pour assurer un taux élevé de fonctions amines primaires. Ces fonctions pourront être utilisées, successivement, pour l'immobilisation de molécules bioactives afin d'augmenter la biocompatibilité des stents. Les dépôts sont effectués sur des substrats d'acier inoxydable 316L en utilisant un réacteur plasma basse pression (70 kHz). Les différentes techniques d'analyse de surface utilisées (angle de contact, XPS, FTIR-ATR) montrent que les variations de puissance de la décharge et du temps de traitement ne modifient pas significativement la composition chimique de surface des dépôts. Cependant, grâce à une technique de dérivation chimique nous avons mis en évidence une meilleure sélectivité vis-à-vis des fonctions amines primaires pour les couches déposées à faibles valeurs de puissance. En effet, des analyses in-situ de la phase plasmagène (spectrométrie de masse, spectroscopie d'émission optique) révèlent qu'une augmentation de la puissance de la décharge conduit à l'augmentation de son caractère énergétique et, ainsi, à l'augmentation du taux de fragmentation du précurseur. La stabilité des revêtements au lavage dans l'eau de-ionisée a été aussi évaluée. Les dépôts obtenus pour une puissance de la décharge de 2W présentent le meilleur compromis entre rétention des fonctions amines primaires et stabilité. Enfin, nous avons évalué les propriétés d'adhérence des couches après déformation plastique en utilisant le " small punch test ", permettant de reproduire les conditions qu'on retrouve lorsque les stents sont déployés dans les artères. Les dépôts présentent des adéquates propriétés de cohésion et d'adhérence au substrat pour répondre à la déformation sans se fissurer et/ou délaminer. Ces résultats montrent que les couches d'allylamine déposées par procédé plasma basse pression présentent des caractéristiques prometteuses afin d'être utilisées comme revêtement performant pour les stents coronariens. Plasma Polymerized allylamine films deposited on 316L stainless steel

Cardiovascular stents are one of the most widely implanted medical devices, with over 1 million implanted each year in the United States alone. While stent failure modes of restenosis and thrombosis have been widely examined, there is an increasing appreciation of the propensity for stents to fracture and break after implantation. It remains unclear however what causes these fractures, which patients and devices are most susceptible, and whether fracture results in failure of device function. / Engineering and Applied Sciences

Το παρόν πρωτόκολλο σχεδιάστηκε προκειμένου να εκτιμήσει την ασφάλεια και την feasibility των μεταλλικών ενδοπροθέσεων που απελευθερώνουν φαρμακευτικές ουσίες (Drug-Eluting Stents, DES) έναντι των απλών μεταλλικών ενδοπροθέσεων (Bare-Metal Stents, BMS) στο φλεβικό μοντέλο κονίκλου, χρησιμοποιώντας Οπτική Συνεκτική Τομογραφία (Frequency Domain – Optical Coherence Tomography, FD-OCT). Μέθοδοι Δεκατρείς λευκοί κόνικλοι Νέας Ζηλανδίας υποβλήθηκαν σε τοποθέτηση μεταλλικών ενδοπροθέσεων που απελευθερώνουν Zotarolimus (Group DES) στη μία κοινή λαγόνιο φλέβα και απλών μεταλλικών ενδοπροθέσεων (Group BMS) στην απέναντι κοινή λαγόνιο. Τα πρωτογενή καταληκτικά σημεία περιελάμβαναν την τεχνική επιτυχία της τοποθέτησης των μεταλλικών ενδοπροθέσεων καθώς και την σύγκριση της νεοενδοθηλιακής υπερπλασίας ανάμεσα στα δύο υπό μελέτη σύνολα με την βοήθεια την οπτικής συνεκτικής τομογραφίας. Αποτελέσματα Η τεχνική επιτυχία της τοποθέτησης 13 μεταλλικών ενδοπροθέσεων που απελευθερώνουν φαρμακευτικές ουσίες και 13 απλών μεταλλικών ενδοπροθέσεων ήταν 100% (26/26 μεταλλικές ενδοπροθέσεις). Τρεις κόνικλοι πέθαναν (3/13, 23%) μέσα στις πρώτες 45 μέρες. Τα υπόλοιπα 10/13 ζώα (77%) θανατώθηκαν την 90η μέρα από την ημέρα τοποθέτησης των μεταλλικών ενδοπροθέσεων. Οι 20 μεταλλικές ενδοπροθέσεις (stents) αφαιρέθηκαν με επιτυχία. Επιτυχής FD-OCT πραγματοποιήθηκε σε όλα τα τμήματα των κοινών λαγόνιων φλεβών που αφαιρέθηκαν, 10 στο Group DES και 10 στο Group BMS. Δεν υπήρξε στατιστικά σημαντική διαφορά στην μέση νεοενδοθηλιακή υπερπλασία ανάμεσα στα δύο σύνολα (3.02±1.19mm2 στο Group DES, έναντι 2.76±1.17mm2 στο Group BMS). Συμπέρασμα Σε αυτό το πειραματικό πρωτόκολλο, η τοποθέτηση DES στο φλεβικό αγγειακό σύστημα ήταν δυνατή. Η νεοενδοθηλιακή υπερπλασία ήταν παρόμοια και στα δύο σύνολα μετά από περίοδο ελέγχου τριών μηνών. / This protocol was designed to evaluate the safety and feasibility of drug-eluting stents (DES) implantation, as well as to compare their long-term results vs. bare-metal stents (BMS) in a rabbit venous model, using Frequency-Domain Optical Coherence Tomography (FD-OCT). Methods Thirteen New Zealand white rabbits underwent implantation of a Zotarolimus-eluting stent in the iliac vein (Group DES) and a BMS in the contralateral iliac vein (Group BMS). Study’s primary endpoints included technical success and the comparison of in-stent neointimal hyperplasia in the two study groups using ex vivo FD-OCT, at 3 months. Results Thirteen DES and 13 BMS were successfully implanted. Technical success rate was 100% (26/26 stents). Three animals (3/13, 23.0%) died within the first 45 days. The remaining 10/13 animals (77%) were euthanized at the 90th day following stent implantation. The 20 stents were successfully removed. Successful ex vivo FD-OCT was performed in all stent-implanted iliac vein segments; 10 in group DES and 10 in group BMS. There was no statistically significant difference in the mean neointimal thickness (NIT) between the two groups (3.02±1.19mm² in group DES vs. 2.76±1.17mm² in group BMS; p=0.0501). Conclusions In this experimental protocol, DES application in the venous system was safe and feasible. Hyperplasia thickness was similar in both groups after 3 months follow-up.

Mechanical stresses and flow dynamics alteration in a stented artery region are known to stimulate intimal thickening and increase the risk of restenosis, the closure of a revascularized artery. Particle imaging velocimetry (PIV) is an optical flow visualization technique that can be used to characterize the local flow dynamics around different stent structures. However, the usual cylindrical stent geometries present visualization difficulties when using an optical measurement technique such as the PIV technique. Using a flat configuration of a stent model presents advantages over the usual cylindrical model. A planar stent model makes data acquisition easier in planes cutting through the model due to its flat geometry that is compatible with the PIV planar flow investigation technique. Furthermore, with the planar stent configuration model velocity measurements and their associated flow features can be done without inducing refraction of the laser light sheet occurring with the cylindrical model's curvature. The refraction of light should be avoided since measurement errors and reflections are the resulting effects of this laser light plane deviation when passing through the curvature of a cylindrical stent model. / The spatial and temporal distribution of the Wall Shear Stress (WSS), which is believed to be of primary importance in the development of restenosis should be comparable between the flat and the cylindrical stent configuration models. The velocity and shear strain rate distributions will be compared between the flat and cylindrical stent configurations using computational fluid dynamics (CFD) simulations in order to analyse the feasibility of using a flat instead of a cylindrical version of the stent model for PIV experiments. It will be shown that for a physiological pulsatile flow the flat model yields results in shear strain rate spatial and temporal distribution that is comparable to the cylindrical model. A more PIV compatible, efficient and less refractive error prone validated flat model would be advantageous when several stent designs influence on the local hemodynamics around the strut geometries have to be studied quantitatively and optimized.

Disertacijos tikslas yra ištirti didelio impulsų pasikartojimo dažnio pikosekundinių lazerių pritaikomumą medžiagų mikroapdirbimui, bei išaiškinti tokių lazerių spinduliuotės sąveikos su metalais ir siliciu ypatybes. Eksperimentiškai buvo ištirta abliacijos slenksčio ir akumuliacijos koeficiento priklausomybė nuo lazerio impulso trukmės siliciui ir metalams. Sukurtas ir eksperimentiškai patvirtintas modelis optimalioms fokusavimo sąlygoms surasti, siekiant maksimalios abliacijos spartos. Didelei impulso energijai, medžiagos nugarinimo efektyvumas mažėja dėl ekranuojančio plazmos poveikio. Įvairių impulso trukmių lazeriai buvo panaudoti silicio gręžimui bei pjovimui. Paviršiaus spektroskopijos metodais, nustatyta, kad pjovimo metu silicis yra legiruojamas anglimi iki 5 µm gylio iš atmosferoje esančio anglies dvideginio, o susidariusi silicio karbido fazė įtakoja lazerinio pjovimo kokybę silicio bandinio gylyje. Taikant didelio impulsų pasikartojimo dažnio pikosekundinius lazerius sudėtingos formos detalių gamybai, rasti sąryšiai tarp paviršiaus šiurkštumo bei proceso parametrų. Pjaunant lazeriu stentus iš Nitinolio, šilumos nukreipimas nuo ruošinio riboja galimą panaudoti lazerio vidutinę galią ir tuo pačiu pasiekiamą efektyvųjį pjovimo greitį; Vykdant sidabro ir aukso abliaciją pikosekundiniu lazeriu skystyje, generuojamos siauro dydžių skirstinio nanodalelės, kurios sudaro stabilius koloidinius tirpalus. / The objective of the thesis is to investigate applicability of high pulse repetition rate picosecond lasers for microfabrication and to clarify high repetition rate pulse interaction with metals and silicon. The ablation threshold and accumulation rate dependence on the laser pulse duration for silicon and metals has been experimentally studied. The model of optimal focus conditions for the maximum ablation rate was developed and experimentally confirmed. The material evaporation rate decreases duo to plasma screening for high pulse energies. Various pulse length lasers have been used for cutting and drilling of silicon. In this work key properties of laser radiation, radiation absorption, ablation and plasma formation are discussed. Surface spectroscopy methods have shown that laser cutting of silicon in the air leads to the cut surface doping with carbon atoms up to 5 µm depth from carbon dioxide in the atmosphere, and the resulting silicon carbide influences the laser cut quality. Testing of applicability of high pulse repetition rate picosecond lasers for the production of complex shapes, relationships between surface roughness and process parameters were determined. Heat abstraction from the workpiece, during laser cutting of stents from nitinol, limits the potential use of the average laser power and the effective cutting speed The silver and gold picosecond laser ablation in the liquid medium generates a narrow size distribution of nanoparticles, which form a stable... [to full text]

The objective of the thesis is to investigate applicability of high pulse repetition rate picosecond lasers for microfabrication and to clarify high repetition rate pulse interaction with metals and silicon. The ablation threshold and accumulation rate dependence on the laser pulse duration for silicon and metals has been experimentally studied. The model of optimal focus conditions for the maximum ablation rate was developed and experimentally confirmed. The material evaporation rate decreases duo to plasma screening for high pulse energies. Various pulse length lasers have been used for cutting and drilling of silicon. In this work key properties of laser radiation, radiation absorption, ablation and plasma formation are discussed. Surface spectroscopy methods have shown that laser cutting of silicon in the air leads to the cut surface doping with carbon atoms up to 5 µm depth from carbon dioxide in the atmosphere, and the resulting silicon carbide influences the laser cut quality. Testing of applicability of high pulse repetition rate picosecond lasers for the production of complex shapes, relationships between surface roughness and process parameters were determined. Heat abstraction from the workpiece, during laser cutting of stents from nitinol, limits the potential use of the average laser power and the effective cutting speed The silver and gold picosecond laser ablation in the liquid medium generates a narrow size distribution of nanoparticles, which form a stable... [to full text] / Disertacijos tikslas yra ištirti didelio impulsų pasikartojimo dažnio pikosekundinių lazerių pritaikomumą medžiagų mikroapdirbimui, bei išaiškinti tokių lazerių spinduliuotės sąveikos su metalais ir siliciu ypatybes. Eksperimentiškai buvo ištirta abliacijos slenksčio ir akumuliacijos koeficiento priklausomybė nuo lazerio impulso trukmės siliciui ir metalams. Sukurtas ir eksperimentiškai patvirtintas modelis optimalioms fokusavimo sąlygoms surasti, siekiant maksimalios abliacijos spartos. Didelei impulso energijai, medžiagos nugarinimo efektyvumas mažėja dėl ekranuojančio plazmos poveikio. Įvairių impulso trukmių lazeriai buvo panaudoti silicio gręžimui bei pjovimui. Paviršiaus spektroskopijos metodais, nustatyta, kad pjovimo metu silicis yra legiruojamas anglimi iki 5 µm gylio iš atmosferoje esančio anglies dvideginio, o susidariusi silicio karbido fazė įtakoja lazerinio pjovimo kokybę silicio bandinio gylyje. Taikant didelio impulsų pasikartojimo dažnio pikosekundinius lazerius sudėtingos formos detalių gamybai, rasti sąryšiai tarp paviršiaus šiurkštumo bei proceso parametrų. Pjaunant lazeriu stentus iš Nitinolio, šilumos nukreipimas nuo ruošinio riboja galimą panaudoti lazerio vidutinę galią ir tuo pačiu pasiekiamą efektyvųjį pjovimo greitį; Vykdant sidabro ir aukso abliaciją pikosekundiniu lazeriu skystyje, generuojamos siauro dydžių skirstinio nanodalelės, kurios sudaro stabilius koloidinius tirpalus.

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Additional advisors: Peter G. Anderson, Brigitta C. Brott, Jack E. Lemons. Description based on contents viewed Feb. 4, 2008; title from title screen. Includes bibliographical references (p. 69-70).

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed February 25, 2010). PDF text: 1 v. (ca. 280 p. : ill.). UMI publication number: AAT 3386755. Includes bibliographical references. Also available in microfilm and microfiche formats.

OBJETIVO: analisar, por meio de morfometria digital, a reação intimal presente na artéria carótida de suínos submetidos à angioplastia isoladamente e à angioplastia seguida de implante de stent de cromo - cobalto. MATERIAIS E MÉTODOS: em oito suínos sadios foi realizada a angioplastia isolada da artéria carótida comum (ACC) direita e angioplastia com implante de um stent de cromo – cobalto expansível por balão na artéria carótida comum esquerda. Após período de quatro semanas, os animais foram submetidos à eutanásia para a retirada de amostras de tecido arterial e preparo de lâminas histológicas divididas do seguinte modo: grupo 1, segmento médio da artéria carótida comum direita (angioplastia isolada); grupo 2, segmento médio da artéria carótida comum esquerda em localização “intra stent”. As imagens das lâminas foram digitalizadas e analisadas por programa de morfometria digital com cálculo da área luminal, área da camada íntima e área da camada média dos cortes histológicos. A análise estatística foi realizada através da média e desvio padrão das áreas em cada grupo, utilizando-se Teste t de Student. O valor de p<0,05 foi considerado significativo. RESULTADOS: na análise das médias das áreas obtidas, foi encontrada maior hiperplasia em resposta ao implante de stent e diferença estatisticamente significativa quando realizada a comparação entre a área do lúmen (5,841 x 106μm2 X 1,287 x 106μm2), da lâmina elástica interna (6,566 x 106μm2 X 1,287 x 106μm2) e lâmina elástica externa (9,832 x 106μm2 X 4,559 x 106μm2) dos dois grupos (ATP + STENT X ATP; medidas em micrômetros quadrados). Não se observou diferença significativa do ponto de vista estatístico quando se realizou a comparação entre as camadas médias dos dois grupos (3,266 x 106μm2 X 3,271 x 106μm2). CONCLUSÃO: o implante de stent de cromo-cobalto expansível por balão na ACC do suíno gerou um espessamento intimal maior do que aquele produzido apenas pela angioplastia, porém este não foi suficiente para afetar o lúmen arterial. / OBJECTIVE: to analyze, through digital morphometry, the intimal reaction in the carotid artery of pigs submitted to isolated angioplasty and angioplasty followed by implantation of cobalt-chromium stent. MATERIALS AND METHODS: eight healthy pigs had their common carotid artery (CCA) submitted to isolated angioplasty in the right side and angioplasty plus stenting in the left side. Four weeks latter, all animals were submitted to euthanasia for arterial tissue sampling and preparation of histological blades sorted as follows: group 1, middle segment of common right carotid artery (isolated angioplasty); group 2, middle segment of common left carotid artery (intra-stent). Blade images were scanned and analyzed through a digital morphometry program with calculation of luminal, intimal and media layers area in the histological sections. The statistical analysis was performed through mean values and standard deviations of the areas in each group, using the Student’s t-Test. The value of p<0.05 was considered significant. RESULTS: When compare to angioplasty alone, the stent group showed greater hyperplasia in response to implantation regarding the lumen area (5.841 x 106μm2 X 1.287 x 106μm2), the internal elastic lamina area (6.566 x 106μm2 X 1.287 x 106μm2) and the external elastic lamina area (9.832 x 106μm2 X 4.559 x 106μm2). No statistically significant difference was observed when comparing the media layers of both groups (3.266 x 106μm2 X 3.271 x 106μm2). CONCLUSION: angioplasty followed by the implantation of a cobalt-chromium balloon expandable stent in the CCA of the pig creates more intimal thickening than angioplasty alone. Nevertheless intimal thickening was not enough to affect the luminal area thanks to a positive elastic remodeling effect.