Technion Scientists Grow de novo Teconstructive Flaps for Bone and Soft Tissue Repair

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Technion Scientists Grow de novo Teconstructive Flaps for Bone and Soft Tissue Repair

Substantial tissue loss can be the result from different causes, including cancer, injury, and infection. Reconstructive surgery attempts to mitigate the damage. Currently, the clinical “gold standard” in the field of reconstructive surgery is the autograft, which entails harvesting tissue from one part of the patient’s body, and transferring it to the damaged site. F

Prof. Levenberg

or example, to reconstruct the lower jaw, surgeons may harvest a portion of the fibula bone, together with the soft tissue and blood vessels around it, from the patient’s leg. The soft tissue and blood vessels are necessary for the bone to survive in its new location.

As one might imagine, there are significant disadvantages to taking a large chunk out of one’s body, such as considerable pain or all the usual complications associated with a surgery at the donor site. Scientists are therefore looking for alternatives to tissue harvest and moving towards tissue engineering. Although some progress has been made in the field, there are still major challenges to overcome in the search for tissue replacements. The Holy Grail for the scientists is de novo tissue generation. Instead of taking tissues from one part of the body to implant in another, new tissues for implantation would be grown in a lab.

That is where Professor Shulamit Levenberg and her team come in. In the Faculty of Biomedical Engineering at the Technion, the focus of her tissue regeneration lab has been on the formation of complex blood vessel networks in lab-grown tissues. Recently, her team created vascularized soft tissues for implantation using stem cells derived from the dental pulp, that is the soft tissue inside the tooth, together with capillary forming (endothelial) cells. The addition of the dental pulp stem cells promoted the generation of the blood vessels, eventually leading to enhanced tissue remodeling and repair. Using these methods, her team was able to promote regeneration of spinal cord injuries in rats, in a study published in Advanced Healthcare Materials journal (Link).

As previously mentioned, bone implanted as part of reconstructive surgery would need soft tissues to support it and blood vessels to feed it. In a recent study conducted in Prof. Levenberg’s lab, Dr. Idan Redenski and his colleagues were able to tackle the issue. In findings recently published in Advanced Functional Materials (link), the team put together their own vascularized tissue technology with biological bone implants developed at Columbia University by Professor Gordana Vunjak-Novakovic to create a de novo tissue flap containing live bone supported by vascularized soft tissue. This took the concept of implantable bone tissue to a whole different level.

That, however, was only the first stage. Having shown that a mixed tissue flap can be grown, the team proceeded to use the new methodology to repair a bone defect in rats, using a two-step approach. First, an engineered soft tissue flap was implanted. Once it was integrated into the body of the rat, the engineered flap was exposed in a second surgery and used to repair a bone defect, while being supported by major blood vessels next to the defect site. The decellularized bone was exposed and inserted to correct the existing defect while the engineered tissue flap supported it. The results were a complete success: the soft tissue with the blood vessels supporting and feeding the bone led to bridging of the bony defect, with the rat’s cells growing in and replenishing the implant. It was, in fact, a complete recovery, better than anything reconstructive surgery can achieve, and not based patient tissue harvest.

Returning to the concept of a jaw implant, one can hope that one day, based on the methods developed by Prof. Levenberg, Dr. Redenski, and the rest of the team, it will be possible for the patient to receive a lab-grown bone perfectly matching the shape of their face, surrounded by lab-grown soft tissues based on their own cells cultivated on 3-dimensional biomaterials. No major damage to other parts of the patient’s body would be necessary.

After finishing his Ph.D., Dr. Redenski will begin a residency in oral and maxillofacial surgery at the Galilee Medical Centre, where he plans to continue his research with the hope of taking the methods developed in Prof. Levenberg’s lab and implementing them in the clinic.

The following people took part in this research: Dr. Idan Redenski, Shaowei Guo, Majd Machour, Ariel Szklanny, Shira Landau, Ben Kaplan, Roberta I. Lock, Yankel Gabet, Dana Egozi, Gordana Vunjak-Novakovic, and Prof. Shulamit Levenberg. Special thanks go to Bruker-Skyscan for their assistance with the microCT studies, allowing non-invasive and precise observation of the healing process.

For the full article in Advanced Functional Materials click here

Helping Those Who Guard Israel

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Honi Sacks, Richard Sacks, Karen Sacks, Barry Sacks
Photo: Liora Kogan

Brothers Richard (Rick) and Barry Sacks and their families are long-time Technion supporters. They recently chose to help fund Technion’s Program to Support Students in the IDF, a unique program that provides specialized support to students whose education is interrupted by Miluim (reserve duty) service. Due to the intensive nature of a Technion education, and the many Technion students who serve in specialized military roles, the program ensures that the State of Israel remains protected and that students don’t lose precious academic progress while serving their country.

“While we don’t live in Israel, we want to support the State and her citizens in meaningful and impactful ways,” explain Rick and Barry. “As Israel’s oldest university, Technion has always been tied to the survival of the State, with alumni creating systems like the Iron Dome, and the development of research and technology that improves lives and is shared with the rest of the world.”

Rick and Barry are the children of Holocaust survivors, Fela and Joe z”l Sacks, which motivates their deep commitment to ensure that the State of Israel remains a safe and flourishing nation. “If Israel had existed during the War, it could have saved people,” says Rick. “Israel needs to remain strong and Technion is a big part of that defence. When we think of Technion students on the front lines, these young kids defending the State, we are inspired to support them.”

Growing up in Canada, raising families, and achieving professional success, Rick and Barry recognize their good fortune and believe that giving back is a privilege and a responsibility. They also stress the importance of setting an example for their children and grandchildren. Rick and his wife Honi have 7 grandchildren, while Barry and his wife Karen have 5.

“We had a modest upbringing,” Barry explains. “But we always understood tzedakah both as a mitzvah (obligation), and an act of kindness. Giving charity is not a burden, it’s an opportunity to take action, help others, and contribute to Tikkun Olam.”

“If I were to advise others,” says Rick, “I would say to find something you are passionate about and support it. You won’t be sorry.”

Volunteering helps with studies – and vice versa

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Student Lina Maudlej was awarded The Council for Higher Education Award for Social Involvement in the Community for her extensive volunteering activities

At just 26 years of age, Lina Maudlej has already accumulated a very impressive list of projects and achievements including her volunteering activities. In recognition of this, she was recently awarded the Shosh Berlinsky Sheinfeld Award for social involvement in the community. The 10,000 ILS prize is intended to encourage and appreciate students who donate their time and skills to the community.

Ms. Maudlej was born in Kafr Qara in Wadi Ara and attended Al-Qasemi High School in Baqa al-Gharbiyye. “I didn’t have a background in computing at home, but science always interested me – and in high school I was particularly passionate about physics and mathematics. Since I knew that the Technion was the place for these subjects, I signed up and was accepted.”

Ms. Maudlej began her studies at The Andrew and Erna Viterbi Faculty of Electrical Engineering, and after taking several courses at the Henry and Marilyn Taub Faculty of Computer Science, she joined the combined track of the two faculties – computer engineering. After finishing her undergraduate degree, she went on to pursue her master’s, which she is hoping to complete this year under the guidance of Professor Mark Silberstein. Her research, conducted in the Accelerated Systems Laboratory (ACSL), deals with accelerator management in cloud computation systems. Most of the work is focused on building a new operating system that will run computational accelerators such as GPUs while achieving high performance and maximum efficiency by using network accelerators.

“My supervisor always saw great potential in me,” said Ms. Maudlej, “both in my research and in my volunteer work. That is why he was so supportive and helped direct me to places where I could develop myself in unexpected ways. I know that being challenged is the right place for me and working with Prof. Silberstein is the right choice. Every day you learn something new. Science never ends, and the challenge is what makes it interesting.”

 

Lina Maudlej with Itai Dabran

Throughout her undergraduate and graduate years, she hasn’t stopped for a moment. In the final stages of her undergraduate degree she worked at Intel, won an award from Amdocs and led projects in the IT course, the “Internet of Things.” On top of this, she continued with her many and varied volunteer activities, which included expanding Wikipedia into Arabic for math, scientific, and technological subjects; participation in the Landa Project, supporting Arab students; and involvement in the Hasoub NGO, promoting technology and innovation in the Arab sector.

 

 

Professor Dan Geiger, dean of the Henry and Marilyn Taub Faculty of Computer Science with Lina Maudlej

Toward the end of her undergraduate degree, Lina became the facilitator in charge of the “Internet of Things” course in the Computer Science Software Development Center (ICST) led by Itai Dabran, and within this framework mentored many young students. She also led systems development projects for the Technion Social Hub together with various organizations, including the Levchash association. The various projects carried out through the hub helped nonprofits by developing programs to support those organizations in need and matching them with volunteers and donors. In this capacity, she dealt with a reduction in food waste in Israel, supporting needy populations, and recycling.

When asked if volunteering gets in the way of her studies, Ms. Maudlej replied, “On the contrary, volunteering helps studies and increases motivation to learn, and vice versa.” And what’s next? “On one hand, I really like academia so going on to do a Ph.D. is a definite possibility. On the other hand, my research is already very practical, and is carried out in cooperation with industry, so finding a job outside academia is also possible. The Technion teaches us to think, and this is an important and very effective tool wherever you are – either here at the Technion or in industry.”

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New Discoveries by Technion, BGU and HZB Scientists Advance the Understanding of Semiconductors, for the Purpose of Harvesting Solar Energy

Prof. Avner Rothschild

Photovoltaic solar cells are devices that convert sunlight into electricity. Sunlight, however, is available only several hours a day. In order to be used at night, or on cloudy days, energy must be stored to ensure a stable power supply. One approach for doing so is to charge rechargeable batteries during the day, using solar power, and to discharge them to the grid during the night. This requires large-scale battery storage that increases the cost of solar power and is only effective for short-term storage. Long-term seasonal storage requires other solutions.

Dr. Daniel Grave

Another approach, which is the subject of studies by Professor Avner Rothschild from the Technion – Institute of Technology and his research group, is to use photoelectrochemical cells to convert sunlight not into electricity, but into hydrogen fuel produced by splitting water molecules (H2O) into hydrogen (H2) and oxygen (O2). The stored hydrogen can be used later for producing electricity, or put to other uses such as heating, fuelling fuel-cell electric vehicles, and various industrial processes such as steel making, petrochemical refining, and ammonia production.

Yifat Piekner

At the heart of both photovoltaic and photoelectrochemical solar cells is a semiconductor photoabsorber – a material capable of absorbing photons and generating free charge carriers (electrons and holes) that contribute to the photocurrent. But where commercial solar cells use silicon for that purpose, photoelectrochemical cells must rely on other materials that display greater compatibility to the conditions in which the cell must operate, such as stability in aqueous electrolytes. A promising material for that purpose is hematite, an abundant form of iron oxide whose chemical composition is similar to that of rust.

Until now, though, hematite has been frustrating scientists: despite half a decade of research, scientists have been able to obtain from it less than 50% of the solar energy 

conversion efficiency that theory predicts. Prof. Rothschild’s group now shows in a paper in Nature Materials why this is the case and presents a novel way of assessing the actual efficiency limit that might be obtained from hematite and other semiconductors.

The group postulated that the efficiency loss in hematite is not caused solely from charge carrier recombination, a well-known effect that can be mitigated by nanostructuring and light trapping techniques but occurs also due to internal light–matter interaction effects that cannot be mitigated by these approaches. According to their hypothesis, a portion of the electrons excited by absorbed photons are excited into electronic states that cannot move freely within the material. The absorbed photons that give rise to these localized electronic transitions are thus “wasted” without contributing to the photocurrent.

Dr. David Ellis

Using an ultrathin (7 nm) hematite film, the group was able to measure the effect in correlation to wavelength, extracting the so-called wavelength dependent photogeneration yield spectrum. In collaboration with the research group of Professor Roel van de Krol from the Institute for Solar Fuels in Helmholtz-Zentrum Berlin, they measured a similar spectral response of photogenerated charge carriers by another, microwave-based technique. Obtaining similar results by the two different methods serves as a verification of the method and demonstrates that the photogeneration yield is an overlooked, yet fundamental limitation responsible for the underperformance of hematite photoelectrodes for solar energy conversion and storage.

The group’s novel method will allow the characterisation of other materials in the same way they characterised hematite, providing information on the limitations of different materials and giving access to information about light-matter interaction in correlated electron materials with non-trivial opto-electronic properties. This will open the way to more efficient construction of photoelectrochemical cells, giving access to renewable energy and green hydrogen fuel.

The following took part in the research: Dr. Daniel Grave, scientist at the Department of Materials Engineering at Ben Gurion University of the Negev; Dr. David Ellis, Yifat Piekner, Dr. Hen Dotan, Dr. Asaf Kay, and Prof. Avner Rothschild from the Department of Materials Science and Engineering and the Grand Technion Energy Program at the Technion – Israel Institute of Technology; as well as Dr. Moritz Kölbach, Patrick Schnell, Dr. Fatwa Abdi, Dr. Dennis Friedrich, and Prof. Roel van de Krol from the Institute for Solar Fuels at the Helmholtz-Zentrum Berlin. The research leading to these results received funding from the PAT Center of Research Excellence supported by the Israel Science Foundation.

 

Click here for the paper in Nature Materials

Technion Scientists Find Way to Improve Water Purification Technology

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Technion Scientists Find Way to Improve Water Purification Technology

Agricultural irrigation accounts for 80% of water usage in the United States. In Israel, the number is just under 60%. With water being a finite resource, the use of recycled water for irrigation is a significant contributor to water conservation. As part of the purification process necessary in order to safely use recycled water for irrigation, excess sodium should be removed, but some minerals, such as calcium and magnesium, should be retained.

Professor Charles Diesendruck

A high ratio of sodium to calcium and magnesium, also known as Sodium Absorption Ratio, adversely affects soil permeability, negatively impacts water infiltration rate, and damages crops. Over time it can cause the salinization of the soil, and such damage can be hard to reverse. Modern methods of water purification are either non-selective, removing wanted minerals and unwanted salts alike and requiring subsequent remineralization of the water; or expensive and not tunable (i.e., they cannot be dynamically adjusted for different feedwater inputs or for changing effluent requirements).

Capacitive deionization is a novel water treatment technology that aims to improve precisely on this non-selectivity. Capacitive deionization uses two electrodes, which are often made from activated carbon, an inexpensive and widely available material. Applying electric charge to the electrodes causes salts and minerals in the feedwater to migrate into the electrodes and collect in nanopores on them – essentially in microscopic content-specific pockets. When these “pockets” are full, reversing the charge empties them out, and the electrode is ready for use again. The problem with this method is that the electrodes wear out quickly.

Professor Matthew Suss

A breakthrough was recently achieved by Professor Matthew Suss of the Technion Faculty of Mechanical Engineering and Wolfson Department of Chemical Engineering, and his team (Ph.D. students Eric Guyes and Amit Shocron, and master’s student Yinke Chen), in collaboration with Professor Charles Diesendruck of the Technion’s Schulich Faculty of Chemistry, whose main interests are water desalination and energy conservation.

In the team’s system, water flows through two porous electrodes. By sulfonating one of the electrodes – that is, executing a chemical reaction that is cheap and easy to perform – the team was able to produce a capacitive deionization cell that proved effective in reducing the Sodium Absorption Ratio of the feedwater, giving significantly better results than cells with electrodes that were not similarly treated. The electrode was also much more stable than what has previously been described. The team ran 1000 cycles of water treatment through it, without the electrode showing significant deterioration – a record cycle life for a cell of this type.

Ph.D. student Eric Guyes

The process was energetically efficient, and the efficiency can be improved further using already existing methods. The system is also easily tuneable. By changing the voltage and the charging time of the electrodes, different results can be obtained, making the method applicable to various uses, including irrigation and more. The findings could lead to a number of practical applications, since the team managed to improve on all aspects of water purification systems that continue to pose a challenge.

 

 

 

Click here for the paper in Clean Water

Breakthrough in Microscopy: Real-time Measurement of Light Waves Bound to Surfaces

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Breakthrough in Microscopy: Real-time Measurement of Light Waves Bound to Surfaces

Guided waves have attracted great attention in recent decades, stimulating the development of various generation and detection methods. Almost all modern communications rely on the guided waves of optical fibers to conduct enormous amount of information at roughly the speed of light. Large data centers, which are the central hubs for this ocean of information, rely on photonic integrated circuitry – another form of guided light waves – but within a silicon chip, quite like the chips of electrical circuitry. These guided waves do not radiate outside their host structure but still leave a signature in air – a fast-decaying wave called evanescent wave.

Evanescent waves cannot be detected by standard microscopy methods as their energy remains bound to the surface and cannot be seen by the microscope detector. Because of this, designated technologies were developed to detect these waves, using either a small needle approaching the surface, scattering out the electromagnetic power in its vicinity; or by firing electrons on the surface and characterizing their spectrum afterwards. Although these two schemes provide an excellent spatial resolution, they require complex and designated infrastructure, as well as long acquisition times, which currently prevent them from imaging the guided waves in real time.

 

In an article published in Nature Photonics, researchers from Technion – Israel Institute of Technology  present a new approach to imaging evanescent waves that allows, among other things, tackling this challenge with the help of “nonlinear wave-mixing,” a combination of two or more light beams that generate a new electromagnetic wave of a different color. This phenomenon, which requires at least one of the light beams to be very intense, occurs in most semiconductors, dielectrics and metals. The Technion researchers mixed a wide and intense pulsed beam of light with evanescent waves traversing the surface, generating a new light wave that could be subsequently detected by regular means. By doing so, they were able to fully reconstruct the electromagnetic field of the evanescent waves and demonstrated real-time monitoring of changes in the wave pattern.

“The idea to overcome this challenge came to me when I was working on a different project,” said Kobi Frischwasser, the leading author of the manuscript. “I was exploring ways to nonlinearly couple light into confined optical modes, when I realized that it could also work the other way around – the information in such modes can be coupled nonlinearly out. I never imagined that this new microscopy scheme could open up new and, so far, unattainable opportunities for near-field science.”

“Aside from bulk materials, nonlinear wave-mixing naturally takes place at any interface between two materials, making it an ideal platform for nanophotonics – which often deals with light at interfaces,” said Professor Guy Bartal of the Andrew & Erna Viterbi Faculty of Electrical Engineering, who headed the project. “Below some spatial limit, Information remains bound to the surface and cannot be seen by any camera. Our technique “releases” this information into radiation that can be detected – even with a commercial camera!”

The new scheme, termed Nonlinear Near-field Optical Microscopy (NNOM), does not require anything other than a powerful commercial laser source and standard optical components and detectors. According to the researchers, this makes it not only affordable – but also approachable. “You don’t need expensive and complicated tools anymore,” Bartal indicated. “For many applications, all you really need is what you already have in your optics lab.”

In their manuscript, Bartal’s research team, comprised of Kobi Frischwasser, Kobi Cohen, Jacob Kher-Alden, Shimon Dolev, and Shai Tsesses, demonstrated the strength of their scheme in imaging various patterns of electromagnetic surface waves, called surface plasmons, while they change in real-time. “We have been working on simple methods to shape such waves for a while, so it was easy to design field patterns we could freely control,” said Jacob Kher-Alden.

“The interesting bit was the information we could extract,” added Bartal. “By changing the polarization of the high-intensity pulses, we could see different shapes. We then found out that we are not just measuring the evanescent waves, but we can choose what information to take out of them.” Particularly, the team could separate and visualize the information stored on the “spin” of the evanescent waves, i.e. the clockwise and anti-clockwise rotation of the electric field on the interface.

“When you process the optical information in free-space, everything is much easier,” said Kobi Cohen. “We could see the spatial frequency content of the surface waves, not just the real-space shape, and through a reconstruction algorithm, we managed to extract their phase as well. From here on out, the road to a full-field reconstruction was clear.”

Finally, the authors demonstrated the application of NNOM by monitoring the changes in digitally encoded surface waves via the use of a spatial light modulator (SLM). “We wanted to show that this new microscopy scheme can have practical applications,” explained Shai Tsesses. “Since there are times when you need to make sure of the exact evanescent pattern, such as in optical trapping and manipulation experiments or when trying to optically address quantum emitters in nanophotonic platforms.”

“We haven’t even begun to explore the limits of this scheme and its applications,” Frischwasser concluded, “It may very well help us to develop better methods of verification for photonic circuitry. We are very excited about the future, and hope that many groups around the world will join us on our quest.”

The research was funded by the Israel Science Foundation, and was assisted by the Russell Berrie Nanotechnology Institute, the Zisappel Micro-Nano fabrication unit and the photovoltaic lab at the Technion. Shai Tsesses is funded by the Israel Academy of Sciences and Humanities through the Adams fellowship program, while Jacob Kher-Alden is funded by a scholarship from the Israeli Council for Higher Education’s Planning and Budgeting Committee.                  

Click here for the paper in Nature Photonics

Scientists Use Machine Learning to Pave the Way for the Design of Antivirals

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Scientists Use Machine Learning to Pave the Way for the Design of Antivirals

Why are there no drugs that can cure Covid, SARS, or the flu? Why is it that if you have a strep throat, you get prescribed an antibiotic, but with a virus, you are told to sit it out? In short, why are there no antivirals in similar quantity, variety, and effectiveness as antibiotics?

Unlike antibiotics, antiviral drugs are typically designed to target one virus. This narrowness of scope makes it uneconomical for drug companies to invest in developing new antivirals. As a result, non-HIV therapeutics comprise less than 1% of the total therapeutics market, which stands in direct contrast to the dominance of infectious diseases in everyday human experience. While the obvious solution to this problem is to develop antivirals that can be used to treat multiple infectious diseases, finding such broad-spectrum drugs has proven to be a highly elusive goal for the scientific community.

Prof. Roee Amit

A groundbreaking study conducted in collaboration between the laboratory of Prof. Roee Amit of the Technion – Israel Institute of Technology’s Faculty of Biotechnology and Food Engineering and the group of Prof. Yaron Orenstein from the School of Electrical and Computer Engineering at Ben-Gurion University of the Negev provides a feasible pathway forward to achieving this goal. The study, led by Dr. Noa Katz, demonstrates that a combined synthetic biology and machine learning approach can result in the discovery of molecules which can bind proteins from two distinct viruses.

Prof. Yaron Orenstein

The traditional method for identifying therapeutics is to apply a low-throughput and labor-intensive screen for molecules that might perform the required function. In contrast, the synthetic biology and machine learning approach seeks to map the “space” of potential interactions so that molecules with the desired properties can be reliably predicted. This is done by first generating a large and high quality experimental dataset from a library (i.e. collection) of various known and suspected potential virus-protein-binding molecules. The dataset is then used to train a neural network to allow it to form a multidimensional mathematical function representing the collective’s protein-binding capability.

Dr. Noa Katz

Once computed, such a function can then be used in reverse. Namely, it can be used to identify regions of high binding capability, and extract “predicted” molecules not previously tested. These unseen or predicted molecules can then be synthesized 

Eitamar Tripto

and tested for the desired biological functionality.  The researchers applied this approach to first map out the binding space of two distinct coat proteins from two different bacteria-attacking viruses, and then synthesized and validated RNA molecules that were predicted to be at the interface between the two spaces, and which therefore possess both functionalities.  This achievement provides the scientific community with a blueprint

 for an approach that can be used to identify novel RNA sequences that could potentially become key ingredients of broad-spectrum anti-viral drugs.

Click here for the paper in Nature Communication