המחברים מודים לפרופסור יו פנג, ד"ר ג'נה ברידל, איאן וודוורד ולוקאס אטיה על הדיונים המועילים ביניהם.

<ol>
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How Medical 3D Printing is Gaining Ground in Top Hospitals Available from: <a target="_blank" href="https://www.materialise.com/en/blog/3d-printing-hospitals">https://www.materialise.com/en/blog/3d-printing-hospitals</a> (2019)</li><li>Weber, P. W., Price, O. T., McClellan, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Demographic+Variability+of+Inhalation+Mechanics:+A+Review.">Demographic Variability of Inhalation Mechanics: A Review.</a> Defense Threat Reduction Agency. , (2016).</li><li>Jiang, Y. Y., Xu, X., Su, H. L., Liu, D. 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F., Ghanbarzadeh, S., Nokhodchi, A., Hamishehkar, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+different+coating+materials+on+the+prevention+of+powder+bounce+in+the+next+generation+impactor.">The effect of different coating materials on the prevention of powder bounce in the next generation impactor.</a> Research in Pharmaceutical Sciences. 13 (3), 283-287 (2018).</li><li>Galliger, Z., Vogt, C. D., Panoskaltsis-Mortari, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=3D+bioprinting+for+lungs+and+hollow+organs.">3D bioprinting for lungs and hollow organs.</a> Translational Research. 211, 19-34 (2019).</li><li>Schwarz, K., Biller, H., Windt, H., Koch, W., Hohlfeld, J. 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למחברים אין מה לחשוף.

המכשיר הנוכחי המדינה-of-the-art עבור בדיקות תרופות ריאתי של מינון שאיפה מלאה הוא המשפיע גנרטור הבא (NGI), אשר מודד את הקוטר האווירודינמי שלתרסיס 4. נתוני גודל זה משמשים לאחר מכן כדי לחזות את ייצור הריאות שבו התרסיס יפקיד בהתבסס על מתאם שפותח עבור זכר בוגר בריא11. למרבה הצע...

מחלות ריאות רבות כגון סרטן ריאות ומחלת ריאות חסימתית כרונית (COPD) להפגין הבדלים אזוריים במאפייני המחלה; עם זאת, יש חוסר טכניקות טיפוליות זמין למקד משלוח סמים רק לאזורים חולים של הריאה1. מודלים רבים של דינמי נוזלים חישוביים (CFD) הוכיחו כי ניתן לווסת פרופילי תצהיר סמים על ידי זיהוי התייעלות ספציפית בריאה2,3. פיתוח משאפים ומתאמי צינור אנדוטראצ'י (ET) עם יכולות מיקוד אזוריות מתבצע במעבדה שלנו כדי לשלוט בחלוקת תרסיסים לאזורי ריאות חולים. הרחבת עקרונות אלה לשימוש קליני מוגבלת על ידי יכולת הבדיקה הפרה-קלינית הנוכחית. המיקום המדויק של מרבצי סמים בתוך הריאה ידוע כמנבא היעילות הטוב ביותר; עם זאת, הערכות התרופות הנוכחיות של טיפולי שאיפה צפויות לרוב באמצעות מתאמי ויוו במבחנה בגודל חלקיקים לתצהיר משוערבלבד 4. טכניקה זו אינה מאפשרת כל ניתוח מרחבי כדי לקבוע את ההשפעות של גיאומטריות דרכי הנשימה השונות על התפלגות אזורית באמצעות האונות השונות של הריאה. בנוסף, בדיקה זו חסרה גיאומטריות ריאות מדויקות אנטומית, אשר חוקרים הראו יכולה להיות השפעה משמעותית על פרופילי תצהיר5. נעשו כמה מאמצים לשלב גיאומטריות ריאה ספציפיות למטופל בפרוטוקולי בדיקה באמצעות תוספת של דרכי הנשימה העליונות; עם זאת, רוב הגישות הללו מדגמות משלוח אירוסול לדורות שונים של הריאה ולא לכל אונה ריאה6,7,8. הפרוטוקול הבא מציג שיטת תפוקה גבוהה של יצירת מודלים ריאות ספציפיים למטופל עם היכולת לכמת תצהיר חלקיקים יחסי בכל אחת מחמש האונות של הריאה9.
ריאות מודל מדויק אנטומית נוצרות על ידי סריקות טומוגרפיה ממוחשבת (CT) של חולה הדפסה תלת מימדית. כאשר משתמשים בו בשילוב עם מערכת זרימה המורכבת בקלות, ניתן לשלוט באופן עצמאי בקצב הזרימה היחסי דרך כל אחת מהאונה של הריאה המודלית ולהתאים אותה לחיקוי אלה של דמוגרפיה של חולים שונים ו/או מצבי מחלה שונים. בשיטה זו, החוקרים יכולים לבדוק את היעילות של שיטות טיפוליות פוטנציאליות בגיאומטריית ריאות רלוונטית ולתאם את הביצועים של כל שיטה עם התקדמות המורפולוגיה החולה. כאן, שני עיצובים מכשיר שפותחו במעבדה שלנו נבדקים על יכולתם להגדיל את התצהיר באונה הריאה הרצויה על ידי שליטה על המיקום של שחרור תרסיס בפה או קנה הנשימה. פרוטוקול זה יש גם פוטנציאל להשפיע באופן משמעותי על התפתחות הליכים מותאמים אישית עבור חולים על ידי הקלת חיזוי מהיר של יעילות הטיפול בריאה מודל ספציפי לנתוני סריקת CT של המטופל.

<table>
	<tbody>
		<tr>
			<td>1/4&#34; Plastic Barbed Tube Fitting</td>
			<td>McMaster Carr</td>
			<td>5372K111</td>
			<td></td>
		</tr>
		<tr>
			<td>10 um Filter Paper</td>
			<td>Fisher</td>
			<td>1093-110</td>
			<td></td>
		</tr>
		<tr>
			<td>1um Fluorescent Polystyrene Particles</td>
			<td>Polysciences</td>
			<td>15702-10</td>
			<td></td>
		</tr>
		<tr>
			<td>1um Non-Fluorescent Polystyrene Particles</td>
			<td>Polysciences</td>
			<td>8226</td>
			<td></td>
		</tr>
		<tr>
			<td>2-Propanol</td>
			<td>Fisher</td>
			<td>A516-4</td>
			<td>Referred to in protocol as &#34;IPA&#34;</td>
		</tr>
		<tr>
			<td>3/8&#34; Plastic Barbed Tube Fitting</td>
			<td>McMaster Carr</td>
			<td>5372K117</td>
			<td></td>
		</tr>
		<tr>
			<td>Air Flow Meter (1 - 280 mL/min)</td>
			<td>McMaster Carr</td>
			<td>41695K32</td>
			<td>Referred to in protocol as &#34;flow meter&#34;</td>
		</tr>
		<tr>
			<td>Carbon M1 3D Printer</td>
			<td>Carbon 3D</td>
			<td></td>
			<td>https://www.carbon3d.com/, Associated software referred to in protocol as &#34;slicing software&#34;</td>
		</tr>
		<tr>
			<td>Collison Jet Nebulizer</td>
			<td>CH Technologies</td>
			<td>ARGCNB0008 (CN-25)</td>
			<td>6 Jet MRE style horizontal collision with glass jar, Referred to in protocol as &#34;nebulizer&#34;, http://chtechusa.com/Manuals/MRE_Collison_Manual.pdf</td>
		</tr>
		<tr>
			<td>Convection Oven</td>
			<td>Yamato</td>
			<td>DKN602</td>
			<td></td>
		</tr>
		<tr>
			<td>Copley Critical Flow Controller TPK2000 Reve 120V</td>
			<td>MSP Corp</td>
			<td>0001-01-9810</td>
			<td>Referred to in protocol as &#34;flow controller&#34;</td>
		</tr>
		<tr>
			<td>Copley High Capacity Pump Model HCP5</td>
			<td>MSP Corp</td>
			<td>0001-01-9982</td>
			<td>Referred to in protocol as &#34;vacuum pump&#34;</td>
		</tr>
		<tr>
			<td>Cytation</td>
			<td>BioTek</td>
			<td>CYT5MPV</td>
			<td>Multifunctional Spectrophotometer/Fluorescent imager equiped with 4x/20x/40x objectives and DAPI/GFP/TexasRed laser/filter cubes</td>
		</tr>
		<tr>
			<td>EPU40 Resin</td>
			<td>Carbon 3D</td>
			<td></td>
			<td>https://www.carbon3d.com/materials/epu-elastomeric-polyurethane/, Referred to in protocol as &#34;soft resin&#34;</td>
		</tr>
		<tr>
			<td>Filter for vacuum pump</td>
			<td>Whatman</td>
			<td>6722-5000</td>
			<td></td>
		</tr>
		<tr>
			<td>Flow Meter Model DFM 2000</td>
			<td>MSP Corp</td>
			<td>0001-01-8764</td>
			<td>Referred to in protocol as &#34;electronic flow meter&#34;</td>
		</tr>
		<tr>
			<td>ImageJ Software</td>
			<td>ImageJ</td>
			<td></td>
			<td>https://imagej.nih.gov/ij/download.html</td>
		</tr>
		<tr>
			<td>Inline Air Flow Control Valve (Push-to-Connect)</td>
			<td>McMaster Carr</td>
			<td>62005K333</td>
			<td>Referred to in protocol as &#34;valve&#34;</td>
		</tr>
		<tr>
			<td>Inline Filter Devices</td>
			<td>Whatman</td>
			<td>WHA67225000</td>
			<td></td>
		</tr>
		<tr>
			<td>Marine-Grade Plywood Sheet</td>
			<td>McMaster Carr</td>
			<td>62005K333</td>
			<td>Referred to in protocol as &#34;wooden board&#34;</td>
		</tr>
		<tr>
			<td>Materialise Mimics Software</td>
			<td>Materialise</td>
			<td></td>
			<td>https://www.materialise.com/en/medical/mimics-innovation-suite, Referred to in protocol as &#34;CT scan software&#34;</td>
		</tr>
		<tr>
			<td>Meshmixer Software</td>
			<td>Autodesk</td>
			<td></td>
			<td>http://www.meshmixer.com/, Referred to in protocol as &#34;mesh editing software&#34;</td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Fisher</td>
			<td>A454-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Opticure LED Cube</td>
			<td>APM Technica</td>
			<td>102843</td>
			<td>Referred to in protocol as &#34;UV oven&#34;</td>
		</tr>
		<tr>
			<td>PR25 Resin</td>
			<td>Carbon 3D</td>
			<td></td>
			<td>https://www.carbon3d.com/materials/uma-urethanemethacrylate, /Referred to in protocol as &#34;hard resin&#34;</td>
		</tr>
		<tr>
			<td>PVC Tube for Chemicals</td>
			<td>McMaster Carr</td>
			<td>5231K161</td>
			<td>1/4&#34; ID</td>
		</tr>
		<tr>
			<td>Screws</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>SolidWorks Software</td>
			<td>Dassault Syst&#232;mes&#160;SolidWorks Corporation</td>
			<td></td>
			<td>https://www.solidworks.com/, Referred to in protocol as &#34;3D modeling software&#34;</td>
		</tr>
		<tr>
			<td>Straight Flow Rectangular Manifold</td>
			<td>McMaster Carr</td>
			<td>1125T31</td>
			<td></td>
		</tr>
		<tr>
			<td>Tubing to Flow Controller</td>
			<td>McMaster Carr</td>
			<td>5233K65</td>
			<td>3/8&#34; ID</td>
		</tr>
		<tr>
			<td>Wire</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluating regional pulmonary deposition using patient-specific 3d printed lung models

פיתוח טיפולים ממוקדים למחלות ריאות מוגבל על ידי הזמינות של שיטות בדיקה פרה-קוליניות עם היכולת לחזות משלוח אירוסול אזורי. מינוף הדפסה תלת-ממדית כדי ליצור מודלים ספציפיים לריאות המטופל, אנו מתארים את העיצוב של תפוקה גבוהה, התקנה ניסיונית במבחנה לכימות תצהיר ריאות לובלי. מערכת זו נעשית עם שילוב של רכיבים מסחריים זמינים ותל"ד מודפסים ומאפשרת את קצב הזרימה דרך כל האונה של הריאה להיות נשלט באופן עצמאי. מסירת אירוסולים פלואורסצנטיים לכל אונה נמדדת באמצעות מיקרוסקופ פלואורסצנטי. לפרוטוקול זה יש פוטנציאל לקדם את הצמיחה של רפואה מותאמת אישית למחלות בדרכי הנשימה באמצעות יכולתו לדגמן מגוון רחב של דמוגרפיה של חולים ומדינות מחלה. ניתן לווסת בקלות הן את הגיאומטריה של מודל הריאות המודפסות בתלת-ממד והן את הגדרת פרופיל זרימת האוויר כדי לשקף נתונים קליניים עבור חולים עם גיל, גזע ומין משתנים. מכשירי אספקת תרופות רלוונטיים קלינית, כגון הצינור endotracheal המוצג כאן, ניתן לשלב לתוך מערך הבדיקה כדי לחזות בצורה מדויקת יותר את היכולת של המכשיר למקד משלוח טיפולי לאזור חולה של הריאה. הרבגוניות של התקנה ניסיונית זו מאפשרת לו להיות מותאם אישית כדי לשקף שפע של תנאי שאיפה, שיפור הקשיחות של בדיקות טיפוליות פרה-קוליניות.

חלקיקים בטווח גודל זה (1-5 מיקרומטר) ותנאי זרימה (1-10 L /min) עוקבים אחר קווי זרם הנוזלים המבוססים הן על מספר סטוקס התיאורטי שלהם והן על נתוני vivo; לכן, בהיעדר מכשיר משלוח ממוקד, חלקיקים המשתחררים למודל הריאות צפויים להפקיד בהתאם לאחוז זרימת האוויר הכוללת המופנית לכל אונה. לאחר מכן ניתן להשוות את ?...

Watch this Scientific Journal Video about Evaluating Regional Pulmonary Deposition using Patient-Specific 3D Printed Lung Models at JoVE.com

Evaluating Regional Pulmonary Deposition using Patient-Specific 3D Printed Lung Models

אנו מציגים תפוקה גבוהה, בשיטת במבחנה לכימות תצהיר ריאתי אזורי ברמת האונה באמצעות CT סריקה נגזר, מודלים של ריאות מודפסות 3D עם פרופילי זרימת אוויר מתכווננת.

הערכת תצהיר ריאתי אזורי באמצעות דגמי ריאות מודפסים תלת-ממדיים ספציפיים למטופל

Development of targeted therapies for pulmonary diseases is limited by the availability of preclinical testing methods with the ability to predict ...

evaluating-regional-pulmonary-deposition-using-patient-specific-3d

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

4.2K Views.  University of Delaware. אנו מציגים תפוקה גבוהה, בשיטת במבחנה לכימות תצהיר ריאתי אזורי ברמת האונה באמצעות CT סריקה נגזר, מודלים של ריאות מודפסות 3D עם פרופילי זרימת אוויר מתכווננת.

Video: Evaluating Regional Pulmonary Deposition using Patient-Specific 3D Printed Lung Models

Patient-specific Modeling of the Heart: Estimation of Ventricular Fiber Orientations

Patient-specific simulations of heart (dys)function aimed at personalizing cardiac therapy are hampered by the absence of in vivo imaging technology for clinically acquiring myocardial fiber orientations. The objective of this project was to develop a methodology to estimate cardiac fiber orientations from in vivo images of patient heart geometries. An accurate representation of ventricular geometry and fiber orientations was reconstructed, respectively, from high-resolution ex vivo structural magnetic resonance (MR) and diffusion tensor (DT) MR images of a normal human heart, referred to as the atlas. Ventricular geometry of a patient heart was extracted, via semiautomatic segmentation, from an in vivo computed tomography (CT) image. Using image transformation algorithms, the atlas ventricular geometry was deformed to match that of the patient. Finally, the deformation field was applied to the atlas fiber orientations to obtain an estimate of patient fiber orientations. The accuracy of the fiber estimates was assessed using six normal and three failing canine hearts. The mean absolute difference between inclination angles of acquired and estimated fiber orientations was 15.4 &deg;. Computational simulations of ventricular activation maps and pseudo-ECGs in sinus rhythm and ventricular tachycardia indicated that there are no significant differences between estimated and acquired fiber orientations at a clinically observable level.The new insights obtained from the project will pave the way for the development of patient-specific models of the heart that can aid physicians in personalized diagnosis and decisions regarding electrophysiological interventions.

A methodology to estimate ventricular fiber orientations from in vivo images of patient heart geometries for personalized modeling is described. Validation of the methodology performed using normal and failing canine hearts demonstrate that that there are no significant differences between estimated and acquired fiber orientations at a clinically observable level.

דוגמנות מטופל ספציפי של לב: אומדן של אורינטציות סיבי חדרית

Patient-specific  simulations of heart (dys)function aimed at personalizing cardiac therapy are hampered  by the absence of in vivo imaging technology for ...

Longitudinal Measurement of Extracellular Matrix Rigidity in 3D Tumor Models Using Particle-tracking Microrheology

The mechanical microenvironment has been shown to act as a crucial regulator of tumor growth behavior and signaling, which is itself remodeled and modified as part of a set of complex, two-way mechanosensitive interactions. While the development of biologically-relevant 3D tumor models have facilitated mechanistic studies on the impact of matrix rheology on tumor growth, the inverse problem of mapping changes in the mechanical environment induced by tumors remains challenging. Here, we describe the implementation of particle-tracking microrheology (PTM) in conjunction with 3D models of pancreatic cancer as part of a robust and viable approach for longitudinally monitoring physical changes in the tumor microenvironment, in situ. The methodology described here integrates a system of preparing in vitro 3D models embedded in a model extracellular matrix (ECM) scaffold of Type I collagen with fluorescently labeled probes uniformly distributed for position- and time-dependent microrheology measurements throughout the specimen. In vitro tumors are plated and probed in parallel conditions using multiwell imaging plates. Drawing on established methods, videos of tracer probe movements are transformed via the Generalized Stokes Einstein Relation (GSER) to report the complex frequency-dependent viscoelastic shear modulus, G*(&#969;). Because this approach is imaging-based, mechanical characterization is also mapped onto large transmitted-light spatial fields to simultaneously report qualitative changes in 3D tumor size and phenotype. Representative results showing contrasting mechanical response in sub-regions associated with localized invasion-induced matrix degradation as well as system calibration, validation data are presented. Undesirable outcomes from common experimental errors and troubleshooting of these issues are also presented. The 96-well 3D culture plating format implemented in this protocol is conducive to correlation of microrheology measurements with therapeutic screening assays or molecular imaging to gain new insights into impact of treatments or biochemical stimuli on the mechanical microenvironment.

Particle-tracking microrheology can be used to non-destructively quantify and spatially map changes in extracellular matrix mechanical properties in 3D tumor models.

מדידת אורך של תאי מטריקס קשיחות במודלי גידול 3D באמצעות Microrheology מעקב חלקיקים

The mechanical microenvironment has been shown to act as a crucial regulator of tumor growth behavior and signaling, which is itself remodeled and ...

Rapid and Low-cost Prototyping of Medical Devices Using 3D Printed Molds for Liquid Injection Molding

Biologically inert elastomers such as silicone are favorable materials for medical device fabrication, but forming and curing these elastomers using traditional liquid injection molding processes can be an expensive process due to tooling and equipment costs. As a result, it has traditionally been impractical to use liquid injection molding for low-cost, rapid prototyping applications. We have devised a method for rapid and low-cost production of liquid elastomer injection molded devices that utilizes fused deposition modeling 3D printers for mold design and a modified desiccator as an injection system. Low costs and rapid turnaround time in this technique lower the barrier to iteratively designing and prototyping complex elastomer devices. Furthermore, CAD models developed in this process can be later adapted for metal mold tooling design, enabling an easy transition to a traditional injection molding process. We have used this technique to manufacture intravaginal probes involving complex geometries, as well as overmolding over metal parts, using tools commonly available within an academic research laboratory. However, this technique can be easily adapted to create liquid injection molded devices for many other applications.

We have devised a method for low-cost and rapid prototyping of liquid elastomer rubber injection molded devices by using fused deposition modeling 3D printers for mold design and a modified desiccator as a liquid injection system.

דיגום מהיר ועלות נמוכה של מכשירים רפואיים באמצעות 3D מודפס תבניות להזרקת נוזלים

Biologically inert elastomers such as silicone are favorable materials for medical device fabrication, but forming and curing these elastomers using ...

Improving 2D and 3D Skin In Vitro Models Using Macromolecular Crowding

The glycoprotein family of collagens represents the main structural proteins in the human body, and are key components of biomaterials used in modern tissue engineering. A technical bottleneck is the deposition of collagen in vitro, as it is notoriously slow, resulting in sub-optimal formation of connective tissue and subsequent tissue cohesion, particularly in skin models. Here, we describe a method which involves the addition of differentially-sized sucrose co-polymers to skin cultures to generate macromolecular crowding (MMC), which results in a dramatic enhancement of collagen deposition. Particularly, dermal fibroblasts deposited a significant amount of collagen I/IV/VII and fibronectin under MMC in comparison to controls.
The protocol also describes a method to decellularize crowded cell layers, exposing significant amounts of extracellular matrix (ECM) which were retained on the culture surface as evidenced by immunocytochemistry. Total matrix mass and distribution pattern was studied using interference reflection microscopy. Interestingly, fibroblasts, keratinocytes and co-cultures produced cell-derived matrices (CDM) of varying composition and morphology. CDM could be used as &#34;bio-scaffolds&#34; for secondary cell seeding, where the current use of coatings or scaffolds, typically from xenogenic animal sources, can be avoided, thus moving towards more clinically relevant applications.
In addition, this protocol describes the application of MMC during the submerged phase of a 3D-organotypic skin co-culture model which was sufficient to enhance ECM deposition in the dermo-epidermal junction (DEJ), in particular, collagen VII, the major component of anchoring fibrils. Electron microscopy confirmed the presence of anchoring fibrils in cultures developed with MMC, as compared to controls. This is significant as anchoring fibrils tether the dermis to the epidermis, hence, having a pre-formed mature DEJ may benefit skin graft recipients in terms of graft stability and overall wound healing. Furthermore, culture time was condensed from 5 weeks to 3 weeks to obtain a mature construct, when using MMC, reducing costs.

Improving 2D and 3D Skin In Vitro Models Using Macromolecular Crowding

We present a protocol to obtain cell-derived matrices rich in extracellular matrix proteins, using macromolecular crowders (MMC). In addition, we present a protocol which incorporates MMC in 3D organotypic skin co-culture generation, which reduces culture time while maintaining maturity of construct.

עור 2D and 3D שיפור<em&gt; במבחנה</em&gt; מודלים שימוש להצטופפות מולקולארית

The glycoprotein family of collagens represents the main structural proteins in the human body, and are key components of biomaterials used in modern ...

Tunable Hydrogels from Pulmonary Extracellular Matrix for 3D Cell Culture

Here we present a method for establishing multiple component cell culture hydrogels for in vitro lung cell culture. Beginning with healthy en bloc lung tissue from porcine, rat, or mouse, the tissue is perfused and submerged in subsequent chemical detergents to remove the cellular debris. Histological comparison of the tissue before and after processing confirms removal of over 95% of double stranded DNA and alpha galactosidase staining suggests the majority of cellular debris is removed. After decellularization, the tissue is lyophilized and then cryomilled into a powder. The matrix powder is digested for 48 hr in an acidic pepsin digestion solution and then neutralized to form the pregel solution. Gelation of the pregel solution can be induced by incubation at 37 &#176;C and can be used immediately following neutralization or stored at 4 &#176;C for up to two weeks. Coatings can be formed using the pregel solution on a non-treated plate for cell attachment. Cells can be suspended in the pregel prior to self-assembly to achieve a 3D culture, plated on the surface of a formed gel from which the cells can migrate through the scaffold, or plated on the coatings. Alterations to the strategy presented can impact gelation temperature, strength, or protein fragment sizes. Beyond hydrogel formation, the hydrogel stiffness may be increased using genipin.

This is a method to create a 3-dimensional cell culture scaffold from pulmonary extracellular matrix. Intact lung is processed into hydrogels that can support the growth of cells in three-dimensions.

הידרוג מתכוונן מ מטריקס ריאתי עבור תרבית תאים 3D

Here we present a method for establishing multiple component cell culture hydrogels for in vitro lung cell culture. Beginning with healthy en bloc lung ...

Scaling of Engineered Vascular Grafts Using 3D Printed Guides and the Ring Stacking Method

Coronary artery disease remains a leading cause of death, affecting millions of Americans. With the lack of autologous vascular grafts available, engineered grafts offer great potential for patient treatment. However, engineered vascular grafts are generally not easily scalable, requiring manufacture of custom molds or polymer tubes in order to customize to different sizes, constituting a time-consuming and costly practice. Human arteries range in lumen diameter from about 2.0-38 mm and in wall thickness from about 0.5-2.5 mm. We have created a method, termed the "Ring Stacking Method," in which variable size rings of tissue of the desired cell type, demonstrated here with vascular smooth muscle cells (SMCs), can be created using guides of center posts to control lumen diameter and outer shells to dictate vessel wall thickness. These tissue rings are then stacked to create a tubular construct, mimicking the natural form of a blood vessel. The vessel length can be tailored by simply stacking the number of rings required to constitute the length needed. With our technique, tissues of tubular forms, similar to a blood vessel, can be readily manufactured in a variety of dimensions and lengths to meet the needs of the clinic and patient.

Scalable engineered blood vessels would improve clinical applicability. Using easily sizable 3D-printed guides, rings of vascular smooth muscle were created and stacked into a tubular form, forming a vascular graft. Grafts can be sized to meet the range of human coronary artery dimensions by simply changing the 3D-printed guide size.

Scaling של שתלי כלי דם שהונדס בשיטות מדריכי 3D מודפס ואת שיטת נחת הטבעת

Coronary artery disease remains a leading cause of death, affecting millions of Americans. With the lack of autologous vascular grafts available, ...

Scaled Anatomical Model Creation of Biomedical Tomographic Imaging Data and Associated Labels for Subsequent Sub-surface Laser Engraving (SSLE) of Glass Crystals

Biomedical imaging modalities like computed tomography (CT) and magnetic resonance (MR) provide excellent platforms for collecting three-dimensional data sets of patient or specimen anatomy in clinical or preclinical settings. However, the use of a virtual, on-screen display limits the ability of these tomographic images to fully convey the anatomical information embedded within. One solution is to interface a biomedical imaging data set with 3D printing technology to generate a physical replica. Here we detail a complementary method to visualize tomographic imaging data with a hand-held model: Sub Surface Laser Engraving (SSLE) of crystal glass. SSLE offers several unique benefits including: the facile ability to include anatomical labels, as well as a scale bar; streamlined multipart assembly of complex structures in one medium; high resolution in the X, Y, and Z planes; and semi-transparent shells for visualization of internal anatomical substructures. Here we demonstrate the process of SSLE with CT data sets derived from pre-clinical and clinical sources. This protocol will serve as a powerful and inexpensive new tool with which to visualize complex anatomical structures for scientists and students in a number of educational and research settings.

Scaled Anatomical Model Creation of Biomedical Tomographic Imaging Data and Associated Labels for Subsequent Sub-surface Laser Engraving SSLE of Glass Crystals

A methodology is described herein for representing anatomical imaging data within crystals. We create scaled three-dimensional models of biomedical imaging data for use in Sub-Surface Laser Engraving (SSLE) of crystal glass. This tool offers a useful complement to computational display or three-dimensionally printed models used within clinical or educational settings.

Scaled אנטומי דגם הבריאה של נתונים הדמיה טומוגרפית ביו Associated תוויות עבור תת-פני השטח לאחר חריטה בלייזר (SSLE) של קריסטלים זכוכית

Biomedical imaging modalities like computed tomography (CT) and magnetic resonance (MR) provide excellent platforms for collecting three-dimensional data ...

Fabrication of Custom Agarose Wells for Cell Seeding and Tissue Ring Self-assembly Using 3D-Printed Molds

Engineered tissues are being used clinically for tissue repair and replacement, and are being developed as tools for drug screening and human disease modeling. Self-assembled tissues offer advantages over scaffold-based tissue engineering, such as enhanced matrix deposition, strength, and function. However, there are few available methods for fabricating 3D tissues without seeding cells on or within a supporting scaffold. Previously, we developed a system for fabricating self-assembled tissue rings by seeding cells into non-adhesive agarose wells. A polydimethylsiloxane (PDMS) negative was first cast in a machined polycarbonate mold, and then agarose was gelled in the PDMS negative to create ring-shaped cell seeding wells. However, the versatility of this approach was limited by the resolution of the tools available for machining the polycarbonate mold. Here, we demonstrate that 3D-printed plastic can be used as an alternative to machined polycarbonate for fabricating PDMS negatives. The 3D-printed mold and revised mold design is simpler to use, inexpensive to produce, and requires significantly less agarose and PDMS per cell seeding well. We have demonstrated that the resulting agarose wells can be used to create self-assembled tissue rings with customized diameters from a variety of different cell types. Rings can then be used for mechanical, functional, and histological analysis, or for fabricating larger and more complex tubular tissues.

This protocol describes a platform for fabricating self-assembled tissue rings in variable sizes using a customized 3D-printed plastic mold. PDMS negatives are cured in the 3D-printed mold; then agarose is cast in the cured PDMS negatives. Cells are seeded into the resulting agarose wells where they aggregate into tissue rings.

ייצור של בארות Agarose מותאם אישית עבור תא זריעה וטבעת רקמות הרכבה עצמית תוך שימוש בתבניות מודפס 3D

Engineered tissues are being used clinically for tissue repair and replacement, and are being developed as tools for drug screening and human disease ...

Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for movement disorders and is being applied to a growing number of disorders. Computational modeling has been successfully used to predict the clinical effects of DBS; however, there is a need for novel modeling techniques to keep pace with the growing complexity of DBS devices. These models also need to generate predictions quickly and accurately. The goal of this project is to develop an image processing pipeline to incorporate structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) into an interactive, patient specific model to simulate the effects of DBS. A virtual DBS lead can be placed inside of the patient model, along with active contacts and stimulation settings, where changes in lead position or orientation generate a new finite element mesh and solution of the bioelectric field problem in near real-time, a timespan of approximately 10 seconds. This system also enables the simulation of multiple leads in close proximity to allow for current steering by varying anodes and cathodes on different leads. The techniques presented in this paper reduce the burden of generating and using computational models while providing meaningful feedback about the effects of electrode position, electrode design, and stimulation configurations to researchers or clinicians who may not be modeling experts.

The goal of this project is to develop an interactive, patient-specific modeling pipeline to simulate the effects of deep brain stimulation in near real-time and provide meaningful feedback as to how these devices influence neural activity in the brain.

פילוח סיבים עצביים ספינלי לטיפול גירוי מוחי עמוק באמצעות דגמים אינטראקטיביים, מטופל ספציפי

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for ...

High-resolution Patterned Biofilm Deposition Using pDawn-Ag43

Spatial structure and patterning play an important role in bacterial biofilms. Here we demonstrate an accessible method for culturing E. coli biofilms into arbitrary spatial patterns at high spatial resolution. The technique uses a genetically encoded optogenetic construct&#8212;pDawn-Ag43&#8212;that couples biofilm formation in E. coli to optical stimulation by blue light. We detail the process for transforming E. coli with&#160;pDawn-Ag43, preparing the required optical set-up, and the protocol for culturing patterned biofilms using pDawn-Ag43 bacteria. Using this protocol, biofilms with a spatial resolution below 25 &#956;m can be patterned on various surfaces and environments, including enclosed chambers, without requiring microfabrication, clean-room facilities, or surface pretreatment. The technique is convenient and appropriate for use in applications that investigate the effect of biofilm structure, providing tunable control over biofilm patterning. More broadly, it also has potential applications in biomaterials, education, and bio-art.

We demonstrate a method for depositing Escherichia coli bacterial biofilms in arbitrary spatial patterns with a high resolution using optical stimulation of a genetically encoded surface-adhesion construct.

ברזולוציה גבוהה בדוגמת באמצעות התצהיר Biofilm pDawn-Ag43

Spatial structure and patterning play an important role in bacterial biofilms. Here we demonstrate an accessible method for culturing E. coli biofilms ...