עבודה זו נתמכה על ידי קרן AO (S-08-42G) וRISystem AG. ברצוננו להרחיב מאוד גדול &quot;תודה לך!&quot; לצוות של סטפן Zeiter במחקר AO מכון דאבוס, שווייץ בשביל להיות כל כך אדיב ובמאפשר לנו להשתמש במתקנים שלהם או לצילומים של הליך כירורגים זה.

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מחבר רומנו Matthys הנו עובד RISystem AG דאבוס, שווייץ שמייצר את השתלים, מכשירי שתל ספציפיים ומתכלה בשימוש במאמר זה. יש הסופר ואידה גלאט אין אינטרסים כלכליים מתחרים.

השלבים הקריטיים ביותר של הליך כירורגי כדי ליצור פגם עצם גדול הם: 1) בחירת משקל הגוף המתאים של החולדה כדי להתאים את הגודל של תופסנים החיצוניים; 2) שמירה על סביבת סטרילית במהלך ההליך; ו 3) הבא פרוטוקול ההליך כירורגי. המטרות העיקריות של ...

מספר המחקרים השתפרו ההבנה של המנגנונים הביולוגיים המעורבים בתיקון רקמות עצם 1-6 שלנו. ההשפעות של תנאים מכאניים על תיקון עצם כגון צירי, גזירה ותנועות interfragmentary (IFMs) נחקרו רבות 7-15. בשנים האחרונות, יותר ויותר מחקרים החלו לצוץ המתארים את ההשפעה של סביבה מכאנית על ריפוי עצם באמצעות שבר, osteotomy ופגם עצם מגזרי גדול במודלי vivo. לכן, יש צורך בשיטות קיבוע אמין כדי לקבל תוצאות מחקר לשחזור ואמינות. הסביבה המכנית סביב השבר הריפוי היא מאוד חשובה כמו זה קובע את הדרך שבר ירפא. לפיכך, הבחירה של מכשיר קיבוע היא מאוד חשובה וצריך להיות שנבחרה בקפידה בהתאם לעיצוב המחקר, וגורמים אחרים כמו גודל פער והסוג של שבר. תכונות מכאניות של מכשיר הקיבועמחדש אפילו יותר חשוב כאשר לומדים ריפוי הגרמי של פגמי עצם גדולים להקים קיבעון שמספק גודל לא רק קבוע פער לאורך כל תקופת הניסוי של משקל כולל נושאים, אלא גם סביבה מכאנית אידיאלית לעצם הריפוי. תופסנים חיצוניים משמשים בדרך כלל שבבר ודגמי ריפוי גדול פגם עצם ניסיוני כי יש להם יתרון על פני מכשירים אחרים קיבעון. היתרון העיקרי של תופסנים חיצוניים הם שהם מאפשרים לשינוי של הסביבה המכנית באתר הפגם in vivo ללא התערבות משנית, אשר יכול להיות מושגת על ידי שינוי או התאמת בר היציבות של המכשיר במהלך הניסוי כ ריפוי עצם מתקדם. יתר על כן, הוא מאפשר היישום של גירוי מכאני מקומי ספציפי כדי לשפר את התיקון של עצם, וגם מספק את הפוטנציאל למדוד את הנוקשות של רקמת יבלת in vivo. אף על פי כן, ההתקנים יש גם כמה חסרונותהכולל: גירוי של רקמות רכות, זיהומים ושבירת סיכה. לרוע המזל, שתלים כאלה לא היו זמינים &quot;מהמדף&quot; בעת פיתוח השתל, וחוקרים נאלצו עיצוב מותאם אישית תופסנים שלהם לשימוש מיועד. לכן, מגבלה אחת של מחקר בתחום זה היה חוסר שליטה ניסיונית על הסביבה המכנית המקומית בפגם מגזרי גדול כמו גם osteotomies כפי שהוא מרפא. המאפיינים מכאניים של תופסנים חיצוניים מוגדרים על ידי, ויכולים להיות מווסת על ידי, מספר גדול מאוד של משתנים הכוללים: המרחק בין סיכות, קוטר סיכה, חומר הסיכה, מספר הפינים, אורך בר, קיבוע, מספר בר, קיבוע, חומר תופסנים בר, עובי בר, ​​קיבוע ואת המרחק ממשטח העצם לבר, הקיבוע (בקיזוז). באופן מפתיע, רק מיעוט מחקרים נמצא שחקרה את התרומות מכאניות של הרכיבים הבודדיםשל תופסנים או תצורות מסגרת שלמות המשמשים במחקרים במכרסמים 16,18,28. לדוגמא, התוצאות של מחקר אחד הראו כי אחד מהגורמים המרכזיים בקביעת הקשיחות הכוללת של מבנה הקיבעון נשלט על ידי הגמישות של הסיכות ביחס לקיזוז נכסי 28, קוטר וחומר. התוצאות מהמחקרים שתוארו לעיל באופן ברור מצביעות על כך שלדעת הסביבה המכנית המסופקת על ידי מכשיר הקיבוע הוא מאוד חשוב, ובכל זאת, במקרים רבים לא נחקר בפירוט. הנייר הנוכחי מדווח השתלת עיצוב, מפרטים, וin vivo של תופסנים חיצוניים המתייחס לנושא זה. תופסנים זה גם מאפשר לאפנון של הסביבה המכנית כריפוי מתקדם, רכוש, המאפשר המחקר של מיכני הרגישות של שלבים שונים של תהליך ריפוי in vivo. בנוסף, כמו גם הטלת מכונאי מקומי מבוקר ולשעתקסביבת אל, הנגישות שלה מאפשרת גם האפנון של סביבה זו בשלבים שונים של ריפוי עצם. תופסנים עיצבנו התבססו על קיבוע חיצוני, אשר נמצא בשימוש נרחב לקיבוע שבר 16-21 ודגמי פגם גדולים בחיות מעבדה 22-27. ההבדל בין תופסנים החיצוניים שלנו והעיצובים הקיימים האחרים המדווחים בספרות הוא שבר היציבות שלהם מאובטח באמצעות ברגים שיש אחיזה הדוקה עם חוטי קירשנר (K-חוטים). סוג זה של עיצוב דורש ברגים כדי להיות retightened דו שבועי (לפעמים אפילו שבועי) כדי לוודא שהמרחק של הקיזוז נשמר כטעינה מיושמת באמצעות נשיאת משקל כדי למנוע ההתרופפות של בר היציבות. אם התרופפות כזו מתרחשת, היא מאפשרת לתנאי העמסה נוספים לא רצויים כגון זוויתי, רוחבי ותנועות גזירת torsional לעצם הריפוי (המבוסס על ניסיון אישי, תקשורת עם Researchers). ידיעה זו, תופסנים חיצוניים תוכנן ככזה שכאשר את הנוקשות של תופסנים צריכה להיות שונה, זה יושג על ידי הסרת חיבור אלמנטים המצורפים למודול העיקרי שבו סיכות ההרכבה הן מוטבע. In vivo ניסוי הפיילוט בוצע באב טיפוס תופסנים החיצוניים החדש כדי לוודא שהיא עומדת בכל דרישות שהוצעו לפני שהוא מיוצר בכמויות גדולות יותר. המטרה העיקרית למאמר זה היא להציג שיטה כירורגית חדשה לתופסנים חיצוניים המשמשים לפגמי עצם גדולים וosteotomies בחולדה עם היכולת לשנות את קשיחות in vivo במהלך תהליך הריפוי. שיטת קיבוע זו מיושמת בvivo על femora של חולדות.

<table border="0" cellpadding="0" cellspacing="0" width="848">
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			<td height="42" style="height:42px;width:232px;">Name of Material/ Equipment</td>
			<td style="width:283px;">Company</td>
			<td style="width:117px;">Catalog Number</td>
			<td style="width:216px;">Comments/Description</td>
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			<td height="21" style="height:21px;">RatExFix simple 100%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.120</td>
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			<td height="21" style="height:21px;">RatExFix simple 70%</td>
			<td>RISystem AG Davos, Switzerland</td>
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			<td></td>
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			<td height="21" style="height:21px;">RatExFix simple 40%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.121</td>
			<td></td>
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			<td height="21" style="height:21px;">RatExFix simple 10%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.122</td>
			<td></td>
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			<td height="42" style="height:42px;width:232px;">RatExFix Connection element 100%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.130</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 70%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.131</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 40%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.132</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Connection element 10%</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.612.133</td>
			<td></td>
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			<td height="21" style="height:21px;width:232px;">RatExFix Main body</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.611.101</td>
			<td></td>
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			<td height="21" style="height:21px;width:232px;">RatExFix InterlockingScrew</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.412.110</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;">RatExFix Mounting pin 0.85 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.412.100</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">RatExFix Saw Guide 100% 5 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.312.100</td>
			<td></td>
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			<td height="21" style="height:21px;width:232px;">Accu Pen 6V+</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.390.211</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">HandDrill</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.390.130</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Drill Bit 0.79 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.593.203</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Gigly wire saw 0.22 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.100</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Square box wrench 0.70 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.112</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Square box wrench 0.50 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.590.111</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Centering bit 1.00 mm</td>
			<td>RISystem AG Davos, Switzerland</td>
			<td style="width:117px;">RIS.592.205</td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scalpel Blade handle</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scalpel Blade (Size 15)</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Tissue Forceps</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Scissors</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Retractor</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Needle Holder</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Henahan Elevator</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td></td>
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		<tr height="42">
			<td height="42" style="height:42px;width:232px;">S-shape curved dissecting and ligature forceps&#160;</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td>2</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Dressing Forceps</td>
			<td style="width:283px;">Fine Science tools</td>
			<td style="width:117px;"></td>
			<td>2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:232px;">Sterile Fenestrated drape</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sterile gauze</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">5 ml syringe&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>&#160;for irrigation of defect</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">24-27G needle&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>&#160;for irrigation of defect</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">1cc Insulin syringes&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for drug injections</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">sterile saline&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>for bone defect irrigation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">sterile gloves</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to perform surgeries</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">chlorohezadine</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>disinfecting solution for surgical site</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Vicryl suture 4-0 with SH-1</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to suture muscle&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Ethibond suture 3-0&#160;</td>
			<td style="width:283px;">Fisher Scientific</td>
			<td style="width:117px;"></td>
			<td>to suture skin</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isofluorine</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>for anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Buprenorphine</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>analgesia during and after the surgery</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Cefazolin</td>
			<td style="width:283px;">Sigma-Aldrich</td>
			<td style="width:117px;"></td>
			<td>antibiotic during and after the surgery&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sprague-Dawley Rats or any other strain</td>
			<td>Charles River Laboratories International, Inc. (Wilmington, MA USA)&#160;</td>
			<td style="width:117px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models

הסביבה המכנית סביב הריפוי של עצם שבורה היא מאוד חשובה כמו זה קובע את הדרך שבר ירפא. בעשור האחרון חלה התעניינות קלינית רבה בשיפור ריפוי עצם על ידי שינוי הסביבה המכנית באמצעות יציבות הקיבוע מסביב לפצע. אילוץ אחד ממחקר בבעלי חיים פרה קליני בתחום זה הוא חוסר שליטה ניסיונית על הסביבה המכנית המקומית בפגם מגזרי גדול כמו גם osteotomies כפי שהם לרפא. במאמר זה אנו מדווחים על העיצוב ושימוש בתופסנים חיצוניים ללמוד הריפוי של פגמי עצם מגזרי גדולים או osteotomies. מכשיר זה מאפשר לא רק לנוקשות ציריות הנשלטות על נגע העצם כפי שהוא מרפא, אבל זה גם מאפשר השינוי של קשיחות בתהליך ריפוי in vivo. הניסויים שנערכו הראו כי תופסנים הצליחו לשמור על פער פגם הירך 5 מ&quot;מ בחולדות in vivo בכלוב בלתי מוגבלפעילות ללפחות 8 שבועות. כמו כן, אנו לא הבחנו בעיוות או זיהומים, כולל דלקות סיכה במשך כל תקופת ההחלמה. תוצאות אלו מראות כי תופסנים החיצוניים החדש שפותחו שלנו הצליחו להשיג ייצוב לשחזור וסטנדרטי, והשינוי של הסביבה המכנית של פגמי עצם גדול in vivo חולדה וosteotomies גודל השונים. זו מאשרת כי מכשיר הקיבוע החיצוני הוא גם מתאים לחקירות מחקר פרה קליניות תוך שימוש במודל חולדה בתחום התחדשות עצם ותיקון.

מפרטי עיצוב ייצוב של עצם ירך העכברוש עם מערכת הקיבוע החיצונית מאפשר יצירת osteotomies 0.5-5 מ&quot;מ. מערכת תופסנים החיצונית היא תופסנים נעולים חיצוניים עשויים מקיטון polyether אתר (פיק - [הגוף העיקרי]) וסגסוגת טיטניום אלומיניום ניוביום (TAN - [סיכו?...

Watch this Scientific Journal Video about Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models at JoVE.com

Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models

One constraint of preclinical research in the field of bone repair is the lack of experimental control over the local mechanical environment within a healing bone lesion. We report the design and use of an external fixator for bone repair with the ability to change fixator stiffness in vivo.

נוקשות מתכוונן, תופסנים חיצוניים למודלים של עכברי ירך osteotomy ומגזרי עצם הפגם

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there ...

adjustable-stiffness-external-fixator-for-rat-femur-osteotomy

Research

JoVE Journal

Medicine

22.4K Views.  Queensland University of Technology. One constraint of preclinical research in the field of bone repair is the lack of experimental control over the local mechanical environment within a healing bone lesion. We report the design and use of an external fixator for bone repair with the ability to change fixator stiffness in vivo.

Video: Adjustable Stiffness, External Fixator for the Rat Femur Osteotomy and Segmental Bone Defect Models

Models of Bone Metastasis

Bone metastases are a common occurrence in several malignancies, including breast, prostate, and lung. Once established in bone, tumors are responsible for significant morbidity and mortality1. Thus, there is a significant need to understand the molecular mechanisms controlling the establishment, growth and activity of tumors in bone. Several in vivo models have been established to study these events and each has specific benefits and limitations. The most commonly used model utilizes intracardiac inoculation of tumor cells directly into the arterial blood supply of athymic (nude) BalbC mice. This procedure can be applied to many different tumor types (including PC-3 prostate cancer, lung carcinoma, and mouse mammary fat pad tumors); however, in this manuscript we will focus on the breast cancer model, MDA-MB-231. In this model we utilize a highly bone-selective clone, originally derived in Dr. Mundy's group in San Antonio2, that has since been transfected for GFP expression and re-cloned by our group3. This clone is a bone metastatic variant with a high rate of osteotropism and very little metastasis to lung, liver, or adrenal glands. While intracardiac injections are most commonly used for studies of bone metastasis2, in certain instances intratibial4 or mammary fat pad injections are more appropriate. Intracardiac injections are typically performed when using human tumor cells with the goal of monitoring later stages of metastasis, specifically the ability of cancer cells to arrest in bone, survive, proliferate, and establish tumors that develop into cancer-induced bone disease. Intratibial injections are performed if focusing on the relationship of cancer cells and bone after a tumor has metastasized to bone, which correlates roughly to established metastatic bone disease. Neither of these models recapitulates early steps in the metastatic process prior to embolism and entry of tumor cells into the circulation. If monitoring primary tumor growth or metastasis from the primary site to bone, then mammary fat pad inoculations are usually preferred; however, very few tumor cell lines will consistently metastasize to bone from the primary site, with 4T1 bone-preferential clones, a mouse mammary carcinoma, being the exception 5,6.
This manuscript details inoculation procedures and highlights key steps in post inoculation analyses. Specifically, it includes cell culture, tumor cell inoculation procedures for intracardiac and intratibial inoculations, as well as brief information regarding weekly monitoring by x-ray, fluorescence and histomorphometric analyses.

Animal models are frequently utilized to study cancer metastasis to bone. In this protocol we will describe two common methods of tumor inoculation for bone metastasis studies and briefly describe some of the analyses utilized to monitor and quantify these models.

מודלים של גרורות עצם

Bone metastases are a common occurrence in several malignancies, including breast, prostate, and lung. Once established in bone, tumors are responsible ...

Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex&#160;vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex&#160;vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement

The mechanisms leading to the development of intimal hyperplasia (IH) and vein graft failure are still poorly understood. This study describes an ex&#160;vivo system to perfuse human veins under controlled flow and pressure. Furthermore the efficiency of external mesh reinforcement to limit the development of IH was evaluated.

נוהל saphenous אדם הוורידים<em&gt; Ex Vivo</em&gt; זלוף וחיצוני חיזוק

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal ...

A Simple Critical-sized Femoral Defect Model in Mice

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all limb bone fractures fail to heal completely due to the extent of the trauma, disease, or age of the patient. Our ability to improve bone regenerative strategies is critically dependent on the ability to mimic serious bone trauma in test animals, but the generation and stabilization of large bone lesions is technically challenging. In most cases, serious long bone trauma is mimicked experimentally by establishing a defect that will not naturally heal. This is achieved by complete removal of a bone segment that is larger than 1.5 times the diameter of the bone cross-section. The bone is then stabilized with a metal implant to maintain proper orientation of the fracture edges and allow for mobility. 
Due to their small size and the fragility of their long bones, establishment of such lesions in mice are beyond the capabilities of most research groups. As such, long bone defect models are confined to rats and larger animals. Nevertheless, mice afford significant research advantages in that they can be genetically modified and bred as immune-compromised strains that do not reject human cells and tissue.
Herein, we demonstrate a technique that facilitates the generation of a segmental defect in mouse femora using standard laboratory and veterinary equipment. With practice, fabrication of the fixation device and surgical implantation is feasible for the majority of trained veterinarians and animal research personnel. Using example data, we also provide methodologies for the quantitative analysis of bone healing for the model.

Animal models are frequently employed to mimic serious bone injury in biomedical research. Due to their small size, establishment of stabilized bone lesions in mice are beyond the capabilities of most research groups. Herein, we describe a simple method for establishing and analyzing experimental femoral defects in mice.

דגם פגם עצם הירך קריטית בגודל פשוט בעכברים

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all ...

Establishment of a Segmental Femoral Critical-size Defect Model in Mice Stabilized by Plate Osteosynthesis

The use of tissue-engineered bone constructs is an appealing strategy to overcome drawbacks of autografts for the treatment of massive bone defects. As a model organism, the mouse has already been widely used in bone-related research. Large diaphyseal bone defect models in mice, however, are sparse and often use bone fixation which fills the bone marrow cavity and does not provide optimal mechanical stability. The objectives of the current study were to develop a critical-size, segmental, femoral defect in nude mice. A 3.5-mm mid-diaphyseal femoral ostectomy (approximately 25% of the femur length) was performed using a dedicated jig, and was stabilized with an anterior located locking plate and 4 locking screws. The bone defect was subsequently either left empty or filled with a bone substitute (syngenic bone graft or coralline scaffold). Bone healing was monitored noninvasively using radiography and in vivo micro-computed-tomography and was subsequently assessed by ex vivo micro-computed-tomography and undecalcified histology after animal sacrifice, 10 weeks postoperatively. The recovery of all mice was excellent, a full-weight-bearing was observed within one day following the surgical procedure. Furthermore, stable bone fixation and consistent fixation of the implanted materials were achieved in all animals tested throughout the study. When the bone defects were left empty, non-union was consistently obtained. In contrast, when the bone defects were filled with syngenic bone grafts, bone union was always observed. When the bone defects were filled with coralline scaffolds, newly-formed bone was observed in the interface between bone resection edges and the scaffold, as well as within a short distance within the scaffold. 
The present model describes a reproducible critical-size femoral defect stabilized by plate osteosynthesis with low morbidity in mice. The new load-bearing segmental bone defect model could be useful for studying the underlying mechanisms in bone regeneration pertinent to orthopaedic applications.

Although mouse models are invaluable tools for bone tissue engineering, models of long bone defects are sparse. This need motivated development of the present protocol which uses a locking plate with four screws and a dedicated jig to perform and stabilize a reproducible, femoral, critical-size defect with low morbidity.

הקמת דגם פגם קריטי בגודל הירך מגזרית עכברים מיוצב על ידי פלייט Osteosynthesis

The use of tissue-engineered bone constructs is an appealing strategy to overcome drawbacks of autografts for the treatment of massive bone defects. As a ...

An Intramedullary Locking Nail for Standardized Fixation of Femur Osteotomies to Analyze Normal and Defective Bone Healing in Mice

Bone healing models are essential to the development of new therapeutic strategies for clinical fracture treatment. Furthermore, mouse models are becoming more commonly used in trauma research. They offer a large number of mutant strains and antibodies for the analysis of the molecular mechanisms behind the highly differentiated process of bone healing. To control the biomechanical environment, standardized and well-characterized osteosynthesis techniques are mandatory in mice. Here, we report on the design and use of an intramedullary nail to stabilize open femur osteotomies in mice. The nail, made of medical-grade stainless steel, provides high axial and rotational stiffness. The implant further allows the creation of defined, constant osteotomy gap sizes from 0.00 mm to 2.00 mm. Intramedullary locking nail stabilization of femur osteotomies with gap sizes of 0.00 mm and 0.25 mm result in adequate bone healing through endochondral and intramembranous ossification. Stabilization of femur osteotomies with a gap size of 2.00 mm results in atrophic non-union. Thus, the intramedullary locking nail can be used in healing and non-healing models. A further advantage of the use of the nail compared to other open bone healing models is the possibility to adequately fix bone substitutes and scaffolds in order to study the process of osseous integration. A disadvantage of the use of the intramedullary nail is the more invasive surgical procedure, inherent to all open procedures compared to closed models. A further disadvantage may be the induction of some damage to the intramedullary cavity, inherent to all intramedullary stabilization techniques compared to extramedullary stabilization procedures.

This protocol describes an osteosynthesis technique using an intramedullary locking nail for standardized fixation of femur osteotomies, which can be used to analyze normal and defective bone healing in mice.

מסמר נעילת intramedullary עבור קיבוע סטנדרטי של Osteotomies עצם הירך כדי לנתח רגיל ופגום עצם ריפוי עכברים

Bone healing models are essential to the development of new therapeutic strategies for clinical fracture treatment. Furthermore, mouse models are becoming ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

A unique rat liver hilar clamp model was developed for studying the impact of pharmacologic molecules in ameliorating ischemia-reperfusion injury. This model includes direct cannulation of the portal supply to the ischemic liver segment via a branch of the portal vein, allowing for direct hepatic delivery.

שיטה של ​​המגזרים הישירים Intra-כבדית משלוח באמצעות מודל קלאמפ עכברוש הכבד hilar

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and &#181;CT imaging. However, both techniques are only able to distinguish between mineralized and non-mineralized tissue. Consequently, it is impossible to discriminate cartilage from fibrous tissue. In contrast, magnetic resonance imaging (MRI) visualizes anatomical structures based on their water content and might therefore be able to noninvasively identify soft tissue and cartilage in the fracture callus. Here, we report the use of an MRI-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice. The experiments demonstrated that the fixator and a custom-made mounting device allow repetitive MRI scans, thus enabling longitudinal analysis of fracture-callus tissue development.

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur

The evaluation of tissue development in the fracture callus during endochondral bone healing is essential to monitor the healing process. Here, we report the use of a magnetic resonance imaging (MRI)-compatible external fixator for the mouse femur to allow MRI scans during bone regeneration in mice.

אין ויוו הערכה של שבר פיתוח קסם במהלך עצם הריפוי בעכברים שימוש בהתקן התואם ל- MRI Osteosynthesis את העכבר אתי

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The ...

Using a Knee Arthrometer to Evaluate Tissue-specific Contributions to Knee Flexion Contracture in the Rat

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ROM is called a joint contracture and results in increased morbidity. Due to the difficulty of reversing established knee contractures, early detection is important, and hence, knowing risk factors for their development is essential. The rat represents a good model with which the effect of an intervention can be studied due to the similarity of rat knee anatomy to that of humans, the rat's ability to tolerate long durations of knee immobilization in flexion, and because mechanical data can be correlated with histologic and biochemical analysis of knee tissue.
Using an automated arthrometer, we demonstrate a validated, precise, reproducible, user-independent method of measuring the extension ROM of the rat knee joint at specific torques. This arthrometer can be used to determine the effects of interventions on knee joint ROM in the rat.

The goal of the protocol is to measure the extension range of motion of the rat knee. The effects of various diseases that increase the stiffness of the knee joint and the effectiveness of treatments can be quantified.

באמצעות Arthrometer של הברך כדי להעריך את תרומתה רקמות ספציפיות הברך הקופסית כיפוף בחולדה

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ...

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the luminal surface area in arteries thereby reducing adequate blood flow to organs and distal tissues. Clinically, revascularization procedures such as balloon angioplasty with or without stent placement aim to restore blood flow. Although these procedures reestablish blood flow by reducing plaque burden, they damage the vessel wall, which initiates the arterial healing response. The prolonged healing response causes arterial restenosis, or re-narrowing, ultimately limiting the long-term success of these revascularization procedures. Therefore, preclinical animal models are integral for analyzing the pathophysiological mechanisms driving restenosis, and provide the opportunity to test novel therapeutic strategies. Murine models are cheaper and easier to operate on than large animal models. Balloon or wire injury are the two commonly accepted injury modalities used in murine models. Balloon injury models in particular mimic the clinical angioplasty procedure and cause adequate damage to the artery for the development of restenosis. Herein we describe the surgical details for performing and histologically analyzing the modified, pressure-controlled rat carotid artery balloon injury model. Additionally, this protocol highlights how local periadventitial application of therapeutics can be used to inhibit neointimal hyperplasia. Lastly, we present light sheet fluorescence microscopy as a novel approach for imaging and visualizing the arterial injury in three-dimensions.

The rat carotid artery balloon injury mimics the clinical angioplasty procedure performed to restore blood flow in atherosclerotic vessels. This model induces the arterial injury response by distending the arterial wall, and denuding the intimal layer of endothelial cells, ultimately causing remodeling and an intimal hyperplastic response.

עכברוש עורק הראש מבוקר לחץ על פגיעה בבלון מגזרי עם יישום טיפולי Periadventitial

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the ...

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Here, we present a protocol to iatrogenically fracture the shaft of the femur of Wistar albino rats and follow up on the development of the callus. This femur osteotomy model can help researchers evaluate the process of fracture healing and to study how a drug could influence fracture healing.

פרוטוקול לפיתוח מודל אוסטאוטומיה של עצם הירך בחולדות ויסטאר אלבינו

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. ...