Bare Metal פרומגנטי סטנט ללכיד תא האנדותל ושייר
Summary
המטרות שלנו היו לעצב, לייצר ולבדוק סטנטים פרומגנטי ללכידת תא האנדותל. עשרה סטנטים נבדקו לשברים ועוד 10 סטנטים נבדקו למגנטיות עודפים. לבסוף, 10 סטנטים נבדקו ב- מבחנה ו8 יותר סטנטים הושתלו ב -4 חזירים להראות ללכוד תאים ושמירה.
Abstract
יש צורך endothelialization המהיר של סטנטים לב וכלי דם כדי להפחית פקקת סטנט ולהימנע מטיפול אנטי-טסיות שיכול להפחית את הסיכון לדימום. הכדאיות של שימוש כוחות מגנטיים כדי ללכוד ולשמר תאי האנדותל תולדה (EOC) שכותרתו עם חלקיקי תחמוצת ברזל סופר פאראמגנטיים (SPION) הוכחה בעבר. אבל טכניקה זו מחייבת פיתוח של סטנט מכאני פונקציונלי מחומר מגנטי וביולוגי ואחריו חוץ גופייה וב- vivo בדיקות כדי להוכיח endothelialization המהיר. פיתחנו סטנט חלש פרומגנטי מפלדת אל-חלד 2,205 דופלקס באמצעות תכנון בעזרת מחשב (CAD) והעיצוב שלה היה מעודן יותר באמצעות ניתוח אלמנטים סופי (FEA). העיצוב הסופי של סטנט הציג זן עיקרי מתחת לגבול שבר של החומר במהלך crimping והרחבה מכאניים. מאה סטנטים יוצרו ותת-קבוצה שלהם שימשה לבדיקות מכאניות, מילained מדידות שדה מגנטיות, ב- מבחנה ללכוד תאים, וב- vivo מחקרי השתלה. עשרה סטנטים נבדקו לפריסה כדי לוודא אם שנגרמו להם ולהרחבת מעגל crimping ללא כשל. עוד 10 סטנטים היו ממוגנטים באמצעות מגנט ניאודימיום חזק והשדה המגנטי שמרה נמדד. סטנטים הראו כי המגנטיות נשמרת הייתה מספיק כדי ללכוד EOC כותרת SPION במחקרים במבחנה שלנו. לכידת EOC כותרת SPION ושימור אומתו במודלים של בעלי חיים גדולים על ידי השתלת סטנט 1 ממוגנט ו1 סטנט שליטה שאינה ממוגנט בכל אחד מ4 חזירים. עורקי stented היו explanted לאחר 7 ימים ונותחו בהיסטולוגיה. סטנטים חלשים המגנטיים שפותחו במחקר זה היו מסוגלים למשוך ושמירת תאי האנדותל שכותרת SPION אשר יכול לקדם ריפוי מהיר.
Introduction
Patients implanted with vascular stents manufactured from thrombogenic materials like stainless steel, cobalt chromium, and platinum chromium – both bare metal stents (BMS) and drug eluting stents (DES) – need anti-platelet therapy to prevent thrombus formation. BMS heal rapidly, but are subject to late stage restenosis due to incomplete healing. DES require long term anti-platelet therapy due to delayed healing. Anti-platelet therapy administered to avoid thrombosis as a result of incomplete or delayed healing leads to increased bleeding risk and may not be suitable for certain patients1,2. An ideal stent will heal completely and quickly thus avoiding long-term anti-platelet therapy and late stage restenosis. This complete healing can only be achieved if the stent is rapidly coated with a monolayer of endothelial cells after implantation. Coating the stents with biocompatible materials such as gold or other biopolymers has been shown to improve thrombo-resistance, but none of these techniques achieved ideal blood compatibility as may be possible by coating with endothelial cells3,4.
A stent can be coated with endothelial cells post implantation by attracting circulating progenitor cells. This self-seeding technique can be achieved by utilizing ligands and antibodies. But this technique is limited by the low number of circulating endothelial progenitor cells. A promising strategy is to deliver cells directly to the stent immediately following implantation during a short period of blood flow occlusion3,5. This strategy requires a technique for rapidly capturing cells and retaining them on the stent even after restoring blood flow. We have developed a technique in which a magnetic stent is used to attract and retain magnetically-labeled endothelial cells delivered post implantation. To achieve this, a functional BMS with sufficient magnetic properties to capture and retain magnetically-labeled endothelial cells is required6.
In this paper, we discuss the methods for designing, manufacturing, and testing a 2205 stainless steel stent. The stents were designed using CAD and FEA. The manufactured stents were magnetized using a neodymium magnet and the retained magnetic field was measured using a magneto-resistance microsensor probe. We then tested the stents for magnetically-labeled cell capture in a culture dish during our in-vitro experiments. Finally, the stents were tested in-vivo by implanting magnetic and non-magnetic stents in 4 pigs and histologically analyzing the stented arteries.
Protocol
Representative Results
Discussion
פיתחנו סטנט מגנטי שיכול לתפקד כסטנט מתכת חשוף ויכול למשוך תאי האנדותל שכותרת SPION. במחקרים קודמים הכוללים סטנטים מגנטיים, חוקרים השתמשו בסטנטים מצופים ניקל מסחריים וסלילים או משתלב עשויים מחומרים מגנטיים בשל חוסר הזמינות של סטנט פרומגנטי 5,10-14. גם קבוצות אחרות ה…
Declarações
The authors have nothing to disclose.
Acknowledgements
The authors thank Tyra Witt, Cheri Mueske, Brant Newman and Dr. Peter J. Psaltis, MBBS, PhD for their valuable contributions. This study was financially supported by European Regional Development Fund – FNUSA-ICRC (No. CZ.1.05/1.100/02.0123), American Heart Association Scientist Development Grant (AHA #06-35185N), National Institutes of Health (T32HL007111) and The Grainger Innovation Fund – Grainger Foundation.
Materials
| 2205 Stainless steel | Carpenter Technology Corporation | N/A | Round bar stock material |
| Abaqus | Dassault systems | N/A | Software |
| Atropine | Prescription drug. | ||
| Clopidogrel | Commercial name: Plavix. Prescription drug. | ||
| CM-DiI | Life Technologies | V-22888 | Molecular Probes, Eugene, OR |
| Endothelial growth medium-2 | Lonza | CC-3162 | |
| Hand Held Crimping tool | Blockwise engineering | M1-RMC | |
| Hydrochloric acid (HCl) | Sigma Aldrich | MFCD00011324 | CAUTION: wear proptective equipment and handle under fume hood |
| Isoflurane anesthesia | Piramal Critical Care, Inc. | ||
| Isopropyl alcohol | Sigma Aldrich | MFCD00011674 | |
| NdFeB magnet 2" Dia x 1" thick | Amazing magnets | D1000P | Axially magnetized disc magnet with poles on flat faces |
| Over-The-Wire trifold balloon | N/A | N/A | Any commercially available OTW trifold balloon can be used |
| Phosphate buffered saline | Life Technologies | 10010-023 | Commonly known as PBS |
| Sodium Bicarbonate (NaHCO3) | Sigma Aldrich | MFCD00003528 | |
| Sodium pentobarbital | Zoetis | Commercial Name: Sleepaway (26%), FatalPlus, Beuthanasi. Controlled substance to be ordered only by licensed veternarian | |
| SolidWorks | Dassault systems | N/A | Software |
| SpinTJ-020 micro sensor | MicroMagneitcs Sensible Solutions | N/A | Long probe STJ-020 microsensor |
| SPION | Mayo Clinic | N/A | Nanoparticles synthesized internally (Ref: Lee, S. J. et al. Nanoparticles of magnetic ferric oxides encapsulated with poly(D,L latide-co-glycolide) and their applications to magnetic resonance imaging contrast agent. J Magn Magn Mater 272, 2432-2433, doi:DOI 10.1016/j.jmmm.2003.12.416 (2004)) |
| Telazol | Zoetis | Controlled substance to be ordered only by licensed veternarian | |
| Trypsin EDTA | Life Technologies | 25200-056 | Gibco, Grand Island, NY |
| Xylazine | Bayer Animal Health | Commercial name: Rompun. Controlled sunstance to be ordered only by a licensed veternarian |
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