Catheter injectable scaffolds for Tissue Engineering Applications
By Helen Guez Galila
Over the past few decades, tissue engineering has been growing and developing in the biomedical world, as it holds great promise for improving the health and quality of life for millions of people, by developing functional substitutes for damaged or diseased tissues. In some applications, injectable scaffolds, a unique therapeutic method used for tissues that are difficult to reach, are needed. For scaffold materials, hydrogels are preferentially selected due to their network structure and similar compositions to the extracellular matrix. The requirements for polymeric hydrogels for scaffold applications are first of all biocompatibility, as well as other mechanical and physical properties, such as the tensile strength, young's modulus, gelation time, viscosity, porosity, and enzymatic degradation rate.
Catheter delivery of hydrogel-based scaffolds is novel and provides unique challenges and design parameters for the biomaterial. The main goal of this research is to develop and study new hydrogel formulations that can be injected through delicate, long catheters, together with air, and used as porous scaffolds for treating a variety of internal ailments.
Novel hydrogels based on gelatin, with alginate as a polymeric additive and crosslinked by carbodiimide were developed for this purpose. Their mechanical and physical properties were measured and analysed. Comparisons of differing concentrations of gelatin and EDC, as well as those of varying ratios of polymer-to-air foams were done in order to find the optimal polymeric formulation for catheter-based injection into the body. In addition, the influence of injection via catheters of different lengths was studied. Our results showed that gels with 200mg/ml gelatin, 10mg/ml alginate, and 20 mg/ml carbodiimide concentrations are ideal. Using this formulation, foamed polymers with ratios of 1.25:1 and 1:1 (polymer-to-air) displayed optimal mechanical properties. It was also concluded that injection via catheters have no significant effect on any mechanical or physical properties, proving the great potential of this therapy. Finally, it was shown that both tested hydrogel formulations can withstand an ample amount of time with minimal weight loss in 100% humidity
nvironments (i.e. in the human body), as well as almost complete degradation in liquid surroundings, which shows the dynamic ability of our technology to be used in a variety of applications. Moreover, good biocompatibility results were obtained. The studied bioadhesive formulations did not induce any significant toxic effects on human fibroblasts nor on mouse-isolated mesenchymal cells. This study presents proof of the concept of using Gelatin-Alginate hydrogels as injectable scaffolds, and may comprise the basis for future studies, in vivo.
העבודה נעשתה בהנחיית פרופ' מיטל זילברמן
המחלקה להנדסה ביו-רפואית, אוניברסיטת תל-אביב
ההרצאה תתקיים ביום ראשון 10.03.19, בשעה 14:00
בחדר 315, הבניין הרב תחומי, אוניברסיטת תל אביב
School of Mechanical Engineering Seminar Wednesday, May 22, 2019 at 14:00
Wolfson Building of Mechanical Engineering, Room 206
Evolving Concepts by On-line Inferiority Estimation and Elimination
Barak Samina
M.Sc. student of Dr. Amiram Moshaiov
This research is motivated by the need to rationalize the allocation of computational resources during a Pareto-based evolution of Set-based Concepts (SBCs). Such an evolution involves the simultaneous exploration of different design spaces, at both the conceptual and particular solution levels, with respect to multiple optimization objectives. Here, several techniques for an on-line estimation of the inferiority of conceptual solutions are suggested and investigated. Such techniques allow on-line intelligent elimination of inferior concepts, which aims at a reduction of the required computational resources.
To evaluate the effectiveness of the proposed techniques, unique concept-based measures and analysis methodology for evolving SBCs are suggested. Extensive statistical study is carried out to assess and compare the suggested techniques. Based on the statistical results, it is concluded that several of the proposed techniques are effective. It is also shown that the effectiveness varies in accordance with the difficulty level of the solved search problems. These conclusions are in accordance with the well-known optimization theorem of no-free lunch.
Estimation Theory with Side Information for Periodic and Constrained Problems
Abstract
In many practical parameter estimation problems some side information regarding the unknown parameters is available. Types of side information that are commonly encountered in signal processing applications include periodicity, parametric equality and inequality constraints, and sparsity. In this research, we address some fundamental topics in estimation theory in the presence of side information. We exploit the side information by choosing proper cost functions, deriving optimal estimation methods, and developing corresponding performance bounds. In the first stage of this work we have investigated the problem of Bayesian parameter estimation in the presence of periodic side information. In periodic parameter estimation, the commonly used mean-squared-error (MSE) risk is inappropriate, since it does not take into account the periodic nature of the problem. We proposed a new class of Bayesian lower bounds on the mean-cyclic-error. This class can be interpreted as the cyclic-equivalent of the Weiss-Weinstein class of MSE lower bounds. This class was extended to provide Bayesian lower bounds for stochastic filtering with periodic side information. In the second stage of this work, we considered non-Bayesian parameter estimation under differentiable equality constraints. For this type of estimation problem, we defined proper unbiasedness in the Lehmann sense and developed new performance bounds that were shown to be more appropriate than the well-known constrained Cramér-Rao bound. In the third stage of this work, we proposed a method for optimal biased estimation. This method is based on combining Lehmann-unbiasedness under a weighted MSE risk and a penalized likelihood approach. It was shown that this method can be useful for parameter estimation under inequality constraints and can lead to estimators that uniformly outperform the minimum variance unbiased estimator and the maximum likelihood estimator.
School of Mechanical Engineering Seminar Monday, April 15, 2019 at 14:00
Wolfson Building of Mechanical Engineering, Room 206
Modeling and Analysis of Biomechanical Interfaces
Dana Solav, PhD
Research Scientist
Massachusetts Institute of Technology
The prosthetic socket constitutes the mechanical interface between the residual limb of amputees and the artificial prosthesis, and is the most critical component of the lower limb prosthetic system. The main challenge is to design a socket that properly distributes the load across the soft tissues, while preventing stress concentrations in vulnerable regions. Conventional socket design is largely artisanal, non-standard, and insufficiently data-driven. A clear necessity in the field is a computational design framework which is automatic, repeatable, data-driven, and based on scientific rationale. In this talk, I will present a novel framework for the computational design of optimized patient-specific sockets. The first and most important step is obtaining a representative biomechanical model of the residual limb, including its accurate shape, deformation, and mechanical properties. This is exceptionally challenging since these measures have to be obtained in-vivo and the soft-tissue material behavior is complex and non-linear. To this end, I have developed a new imaging setup and software based on 3D digital image correlation, which provides accurate full-field measurements of the entire residuum skin. These measurements can be used in combination with data from MRI and a custom indentation device to identify the material parameters of the underlying soft tissues using inverse finite element (FE) analysis. Furthermore, I will demonstrate the capability of a custom software to iteratively execute FE analyses and use the results to inform modifications in the socket design. Finally, I will present future research directions towards optimized design of prosthetic sockets and application to other biomechanical interfaces.
Short Bio
Dana Solav received a BSc in Geophysics from Tel Aviv University (2006) and a PhD in Mechanical Engineering from the Technion Israel Institute of Technology (2016). In January 2017 she joined the MIT Media Lab’s Biomechatronics group as a postdoctoral fellow, where she became a research scientist (2019) to lead the group’s Computational Biomechanics research track. Her research experience includes continuum mechanics, musculoskeletal modeling, soft tissue biomechanics, and imaging methods. Her current research focuses on combined experimental and computational investigation of the mechanical interface between the residual limb of amputees and the prosthetic socket.
School of Mechanical Engineering Seminar Wednesday, March 13, 2019 at 14:00
Wolfson Building of Mechanical Engineering, Room 206
Tumor dormancy and recurrence: theory & experiment for tumor growth, regression & metastasis
Prof. David S. Rumschitzki
Department of Chemical Engineering, The City College of New York
PhD programs in Chemistry and Biology, Graduate School and University Center, City University of New York
Department 0f Medicine (Cardiology), Columbia Presbyterian Medical Center, Columbia University
Collaborators: Adeyinka Lesi (PhD student), Silja Heilmann (Postdoc), Richard M. White (Professor at Memorial Sloan Kettering Cancer Center)
Certain types of cancer including breast cancer and melanoma can recur many years after apparently successful treatment. It is a mystery how tumor cells can remain dormant for many years, avoid eradication by the immune system and then reactivate after many years. We present a population balance model to describe how the size distribution of an ensemble of tumors from many patients evolves in time due to mitosis, cell death and metastasis. A transformation recasts the dynamic interplay between tumor growth and shrinkage in these equations into the form of an advective-diffusion equation in tumor size space. These new equations predict and thus provide a plausible mechanism for tumor dormancy and recurrence for certain relationships amongst the three model parameters. After showing that our model easily fits data sets on tumor size distributions in the literature, we present new, far more refined gender- and immune status-segregated data on the zebrafish melanoma. We show that our model also describes these data very well. Study of gender-segregated cohorts shows gender-dependent parameter only appears in the host-dependent parameter describing tumor shrinkage; it is far more size-dependent in females than in males, which may be relevant for gender differences in human melanoma outcomes. Fortunately for the fish, their model parameters do not predict recurrence over fish lifetimes. However, the model guides our current experiments by instructing us on how to try to perturb fish immunity to bring fish parameters into the range where we should be able to observe fish melanoma dormancy and recurrence. There are claims in the literature that a mouse model of breast cancer can show dormancy and recurrence. We are beginning a collaboration at the Technion Rambam using this mouse model to test our mathematical model and to see we find dormancy and recurrence theoretically, experimentally or both.
תפקידו וייעודו של המהנדס/ת המכני/ת נמצאים בתהליך מתמיד של התחדשות. הכשרת המהנדס/ת המכנית מאפשרת לעסוק במגוון רחב של תפקידים בנושאים הכוללים: מחקר ופיתוח, תכנון, ייצור, ניהול הנדסי ואחזקה. בנוסף לתחומים הקלאסיים של המהנדס/ת המכני, ההכשרה הבסיסית שמקנים הלימודים במגמה להנדסה מכנית מאפשר לבוגרים ולבוגרות לעסוק בקשת רחבה של תחומים, כגון: הנדסה אווירונאוטית, הנדסת אניות ואוקינוגרפיה, הנדסה גרעינית, הנדסה אזרחית, הנדסת חומרים, הנדסת סביבה, הנדסת מכטרוניקה ורובוטיקה, זיווד אלקטרוני, הנדסת מחשבים והנדסה ביו-רפואית.
תחזיות רבות בדבר הטכנולוגיות המובילות בשנים הבאות כוללות בתוכן את אוסף הנושאים הבא:
ננו-טכנולוגיה
רובוטיקה
אנרגיות חלופיות
איכות הסביבה
ביו-הנדסה/ביו-מכניקה
נושאים אלו ואחרים שנלמדים, נחקרים ומפותחים בהנדסה מכנית צפויים להוביל בתרומה לאיכות חיינו, רווחתנו הכלכלית וביטחוננו. נושאים אלו גם משרתים באופן משמעותי את אותן הטכנולוגיות שיותר פופולריות היום כגון מחשבים. לדוגמה, הבעיות הקשורות בהתפתחות מעבדים קטנים ומהירים יותר נוגעות לחומרים, תהליכי ייצור ומעבר חום שהם נושאי הנדסת מכונות קלאסיים. הנדסה מכנית אם כן, היא תחום תשתית לכל הטכנולוגיות האחרות ובעצמה מובילה טכנולוגיות חדשות מלהיבות.
ממה מושפעת תעשיית ההנדסה המכנית?
בעידן המודרני ההנדסה המכנית מושפעת באופן מכריע מהתפתחות אמצעי המחשוב. כלי רכב, מטוסים, כלי שייט, רובוטים, מכונות ייצור, תחנות כוח, מערכות מיזוג אוויר ולעיתים אף מבנים כגון גשרים, סכרים ובניינים חכמים - מופעלים, מבוקרים ומתוחזקים בעזרת מחשב. תהליכים רבים בתעשייה בת זמננו נמצאים תחת בקרה ממוחשבת. חלק גדול מהתיכון והייצור המכני נתמכים כיום בכלים ממוחשבים. במקביל לתכנון המכני הקלאסי מתפתח בשנים האחרונות שטח חדש של תכנון מכטרוני. המכטרוניקה, המשלבת מכניקה, אלקטרוניקה ומחשבים, היא פועל יוצא של מהפיכת המחשוב.
מה הדגש העיקרי בלימודים?
אסטרטגיה של תכניות הלימוד של ביה"ס היא להקנות לסטודנטים כלים בסיסיים אוניברסליים ויכולות לימוד עצמי לאורך זמן, מבוססים על לימודים נרחבים במדעי היסוד כגון מתמטיקה ופיזיקה ועקרונות של מכניקה קלאסית. ביה"ס מציע כיום, יחד עם התכנית בהנדסה מכנית בתואר ראשון, עוד שתי תכניות לתואר כפול - תואר ראשון כפול בהנדסה מכנית ובמדעי כדור הארץ בדגש סביבה. תכניות לתארים מתקדמים מאפשרות לתלמידים להתעמק במחקרים בתחומים של מדעי הנדסה מכנית. תכנית ייחודית למצטיינים לתואר שני ישיר שמאפשרת השלמת התואר בחמש שנים מושכת תלמידים מצטיינים שמשתלבים במחקר של ביה"ס. אנו מאמינים כי תוכניות הלימוד בהנדסה מכנית מספקות את המענה המתבקש לרב-תחומיות תוך כדי שמירה על תחומי ההוראה והמחקר המסורתיים.
מה אפשרויות התעסוקה לבוגרים?
הבוגרים של תכניות אלה משתלבים בהצלחה בתעשייה ובאקדמיה ותורמים לפתרון האתגרים הקשורים בין היתר לצרכים הביטחוניים של מדינת ישראל, ההתפתחות הכלכלית, תגלית הנפט והגז והשינוי האקלימי - כולם מחייבים שילוב הנדסה מכנית לשמירת הביטחון, הסביבה וההתייעלות האנרגטית.
למי זה הכי מתאים?
לימודי הנדסה מכנית מתאימים לכל מעמד ומועמדת בעלי נתוני קבלה נדרשים. התכונות החשובות הן יצירתיות, רצון להתעמק ברמת ההבנה ויכולת לרדת לעומק הדברים, ראיה מערכתית ובינתחומית וגם תפיסה מרחבית.
