The 3D lab and head and neck surgeons of the Netherlands Cancer Institute have worked for years on this groundbreaking innovation together with the Dutch company Mobius 3D Technologies (M3DT).
After four years of intensive research by the Netherlands Cancer Institute and the Dutch Mobius 3D Technology (M3DT), a titanium lower jaw was implanted for the first time in a head and neck cancer patient. The jaw was completely reconstructed based on the patient's 3D MRI & CT scans. The operation was successful.
Tumors in and around the lower jaw are often treated by removing part of the jaw bone (mandible). The mandible is reconstructed, if possible, with bone from elsewhere in the body (usually from the fibula, a small bone from the lower leg). The disadvantage of these reconstruction methods is that they are complex and require vascular anastomosis and also cause morbidity at the donor site. When using only metal plates, these can break or extrude through mucosa or skin in about 40% of the cases and the screws with which the plate is attached can come loose. This has dramatic consequences for the patient involved. Our new 3D printed mandible exactly fits the defect, has the shape and weight of the original mandible and is much stronger than the currently used plates.
Functions such as talking, drinking, and eating are preserved The implant is much stronger, partly because the forces are optimally distributed with an improved fastening technique. The implant also has a so-called 'mesh structure' on the inside. In this way, the implant retains its strength, while the prosthesis still feels light for the patient (comparable weight of bone is approximated). The implant can no longer break and the innovative orientation of the fixation screws ensures that the implant stays in place. Because the implant is custom-made, the jaw retains its fit and pressure on the overlying mucosa or skin is distributed more evenly. We hope this will diminish complications and improve functional and esthetic outcome. Even the tools the surgeon uses in the operation are patient-specific. The operation is also simpler and shorter.
Unique collaboration The 3D lab and head and neck surgeons of the Netherlands Cancer Institute have worked for years on this groundbreaking innovation together with the Dutch company Mobius 3D Technologies (M3DT). This application is expected to be more widely applicable in 2023/2024. In the meantime, research is underway to further expand these techniques for implants elsewhere in the face and skull. Health Holland has made this development possible by granting an innovation grant.
Combining cauterization, suction, the bioengineering alum designed the medical device he’s hoping to get into every surgeon’s hands.
Where there’s surgery, there’s blood. Every day, surgeons use electrocautery pencils in countless surgeries to open incisions and dissect tissue. But cutting into an organ inevitably causes blood to pool in the wound, blocking the surgeon’s view and causing a delay in the operation while the blood is suctioned away.
Alex Yang, S.B. ‘17, is trying to streamline that process with a new device that’s both an electrocautery pencil and suction tube. He founded ClearCut Surgical earlier this year to produce the device, and his company has secured pre-seed funding from multiple investors.
“Our ultimate goal is to try to get this device into the hands of every surgeon around the world, because this device would be used in every surgery,” says Yang, who is about to begin his last year in the MD/MBA program run jointly by Harvard Business School (HBS) and Harvard Medical School (HMS).
Yang first devised the ClearCut device as an undergraduate studying bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. He spent the summer after his junior year working in the Innovation Digital Health Accelerator at Boston Children’s Hospital, which is how he met Heung Bae Kim, Professor of Surgery at HMS and Weitzman Family Chair in Surgical Innovation at Boston Children’s. Kim and Yang got to chatting, and the challenges of blood accumulation during surgery eventually came up.
“This isn’t a new problem,” Yang says. “Many surgeons have been dealing with this problem for decades. Over the years, Kim had tried to jury-rig a solution, but our serendipitous meeting was finally the catalyst for us sitting down to think about creating a new device.”
From these conversations, ClearCut was born. The handheld device uses buttons to switch between electrocautery pencil and suction tube. The injection-molded plastic device doesn’t require additional electric power, switching functions with a pneumatic piston that connects to the vacuum suction in the wall of the operating room. These innovations keep the cost low, which could help make the device accessible to hospitals in lower-resource areas of the world.
“This device has probably gone through over a hundred iterations and 3D printed designs,” Yang says. “Surgeons are understandably picky, and you really only have one shot to get it right. If the button position is slightly off, or fails one out of a hundred times, or the device feels too clunky, you lose the surgeon right there. For a while, it was 80% to 90% there, but we wanted to make it sure it was 100%.”
Yang has spent the last six years slowly developing the device while pursuing his MD/MBA, soliciting feedback from multiple surgeons within Boston Children’s Hospital. He founded his company in March, and soon after won $30,000 as both Runner-Up and Crowd Favorite at the HBS New Venture Challenge. More recently, ClearCut Surgical was selected as one of 50 start-ups for the MedTech Innovator and Accelerator Challenge, which will announce its prizes in October.
“They’re the biggest medtech accelerator in the world,” Yang notes. “It’s very hard to find a cohort that’s that concentrated and has that many resources. It’s great access to capital, manufacturing partners and industry partners all in one place.”
Designing a device is nothing new for Yang. His senior capstone project, a pediatric lower-limb prosthetic device, won a 2017 Dean’s Award for Outstanding Engineering Project.
“My dad is an architectural model maker and has spent his life building miniature buildings,” Yang says. “From when I was 5 or 6 years old. I was playing around in his workshop with tools, and he’s definitely been an inspiration.”
ClearCut still has to be approved by the U.S. Food and Drug Administration, a process Yang said will likely take at least one more year. He’s eyeing early 2025 for the company’s first commercial roll-out.
Once ClearCut does become available, Yang believes its low cost and ability to solve such a common surgical challenge will make it a hit for surgeons around the world.
“One of the options would’ve been to take the idea, file a patent, and license or sell it to a large medical device company,” Yang says. “But given my experience at SEAS and my engineering know-how, I thought it would be a better use of my time and our money to do it myself and take it as far as I could.”
Capturing tears to detect exosomes, nanometer-sized vesicles found in bodily secretions, have the potential for being diagnostic cancer biomarkers.
Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a contact lens that can capture and detect exosomes, nanometer-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. The lens was designed with microchambers bound to antibodies that can capture exosomes found in tears. This antibody- conjugated signaling microchamber contact lens (ACSM-CL) can be stained for detection with nanoparticle-tagged specific antibodies for selective visualization. This offers a potential platform for cancer pre-screening and a supportive diagnostic tool that is easy, rapid, sensitive, cost-effective, and non-invasive.
Exosomes are formed within most cells and secreted into many bodily fluids, such as plasma, saliva, urine, and tears. Once thought to be the dumping grounds for unwanted materials from their cells of origin, it is now known that exosomes can transport different biomolecules between cells. It has also been shown that there is a wealth of surface proteins on exosomes – some that are common to all exosomes and others that are increased in response to cancer, viral infections, or injury. In addition, exosomes derived from tumors can strongly influence tumor regulation, progression, and metastasis.
Because of these capabilities, there has been much interest in using exosomes for cancer diagnosis and prognosis/treatment prediction. However, this has been hampered by the difficulty in isolating exosomes in sufficient quantity and purity for this purpose. Current methods involve tedious and time-consuming ultracentrifuge and density gradients, lasting at least ten hours to complete. Further difficulties are posed in detection of the isolated exosomes; commonly used methods require expensive and space-consuming equipment.
The TIBI team has leveraged their expertise in contact lens biosensor design and fabrication to eliminate the need for these isolation methods by devising their ACSM-CL for capturing exosomes from tears, an optimum and cleaner source of exosomes than blood, urine, and saliva.
They also facilitated and optimized the preparation of their ACSM-CL by the use of alternative approaches. When fabricating the microchambers for their lens, the team used a direct laser cutting and engraving approach rather than conventional cast molding for structural retention of both the chambers and the lens.
In addition, the team introduced a method that chemically modified the microchamber surfaces to activate them for antibody binding. This method was used in place of standard approaches, in which metallic or nanocarbon materials must be used in expensive clean-room settings.
The team then optimized procedures for binding a capture antibody to the ACSM-CL microchambers and a different (positive control) detection antibody onto gold nanoparticles that can be visualized spectroscopically. Both these antibodies are specific for two different surface markers found on all exosomes.
In an initial validation experiment, the ACSM-CL was tested against exosomes secreted into supernatants from ten different tissue and cancer cell lines. The ability to capture and detect exosomes was validated by the spectroscopic shifts observed in all the test samples, in comparison with the negative controls. Similar results were obtained when the ACSM-CL was tested against ten different tear samples collected from volunteers.
In final experiments, exosomes in supernatants collected from three different cell lines with different surface marker expressions were tested against the ACSM-CL, along with different combinations of marker-specific detection antibodies. The resultant patterns of detection and non-detection of exosomes from the three different cell lines were as expected, thus validating the ACSM-CL’s ability to accurately capture and detect exosomes with different surface markers.
“Exosomes are a rich source of markers and biomolecules which can be targeted for several biomedical applications,” said Ali Khademhosseini, Ph.D., TIBI’s Director and CEO. “The methodology that our team has developed greatly facilitates our ability to tap into this source.”
Additional authors are: Shaopei Li, Yangzhi Zhu, Reihaneh Haghniaz, Satoru Kawakita, Shenghan Guan, Jianjun Chen, Kalpana Mandal, Juchen Guo, Heemin Kang, Wujin Sun, Han-Jun Kim, Vadim Jucaud, Mehmet R. Dokmeci, Pete Kollbaum, Chi Hwan Lee, and Ali Khademhosseini.
Flexible implanted electronics are a step closer toward clinical applications, could treat spinal cord injury and Parkinson’s disease.
A recent breakthrough technology developed by a research team from Griffith University and UNSW Sydney was pioneered by Dr Tuan-Khoa Nguyen, Professor Nam-Trung Nguyen and Dr Hoang-Phuong Phan (currently a senior lecturer at the University of New South Wales) from Griffith University’s Queensland Micro and Nanotechnology Centre (QMNC) using in-house silicon carbide technology as a new platform for long-term electronic biotissue interfaces.
The project was hosted by the QMNC, which houses a part of the Queensland node of the Australian National Nanofabrication Facility (ANFF-Q).
ANFF-Q is a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and microfabrication facilities for Australia’s researchers.
The QMNC offers unique capabilities for the development and characterisation of wide band gap material, a class of semiconductors that have electronic properties lying between non-conducing materials such as glass and semi-conducting materials such as silicon used for computer chips.
These properties allow devices made of these materials to operate at extreme conditions such as high voltage, high temperature, and corrosive environments.
The QMNC and ANFF-Q provided this project with silicon carbide materials, the scalable manufacturing capability, and advanced characterisation facilities for robust micro/nanobioelectronic devices.
“Implantable and flexible devices have enormous potential to treat chronic diseases such as Parkinson’s disease and injuries to the spinal cord,” Dr. Tuan-Khoa Nguyen says.
“These devices allow for direct diagnosis of disorders in internal organs and provide suitable therapies and treatments.
“For instance, such devices can offer electrical stimulations to targeted nerves to regulate abnormal impulses and restore body functions.”
Because of direct contact requirement with biofluids, maintaining their long-term operation when implanted is a daunting challenge.
The research team developed a robust and functional material system that could break through this bottleneck.
“The system consists of silicon carbide nanomembranes as the contact surface and silicon dioxide as the protective encapsulation, showing unrivalled stability and maintaining its functionality in biofluids,” Nguyen says.
“For the first time, our team has successfully developed a robust implantable electronic system with an expected duration of a few decades.”
The researchers demonstrated multiple modalities of impedance and temperature sensors, and neural stimulators together with effective peripheral nerve stimulation in animal models.
Corresponding author Dr Phan says implanted devices such as cardiac pace markers and deep brain stimulators had powerful capabilities for timely treatment of several chronical diseases.
"Traditional implants are bulky and have a different mechanical stiffness from human tissues that poses potential risks to patients. The development of mechanically soft but chemically strong electronic devices is the key solution to this long-standing problem,” Phan says.
The concept of the silicon carbide flexible electronics provides promising avenues for neuroscience and neural stimulation therapies, which could offer live-saving treatments for chronic neurological diseases and stimulate patient recovery.
“To make this platform a reality, we are fortunate to have a strong multidisciplinary research team from Griffith University, UNSW, University of Queensland, Japan Science and Technology Agency (JST) - ERATO, with each bringing their expertise in material science, mechanical/electrical engineering, and biomedical engineering,” Phan says.
Münster surgeons use new operating method for the first time anywhere in the world.
It’s a great success for robotic microsurgery not only in Münster but worldwide – both for medicine and for science: a team led by scientists Dr. Maximilian Kückelhaus and Prof. Tobias Hirsch from the Centre for Musculoskeletal Medicine at the University of Münster has carried out the first completely robot-supported microsurgical operations on humans. The physicians used an innovative operating method in which a new type of operations robot, designed especially for microsurgery, is networked with a robotic microscope. This approach makes it possible for the operating surgeon to be completely taken out of the operating area. The use of robots for clinical research is undertaken in collaboration with Münster University Hospital and Hornheide Specialist Clinic.
The experts have been using this method for a good two months. So far, five operations have been successfully performed, with many more set to follow. “This new method for operations enables us to work with a much higher degree of delicacy and precision than is possible with conventional operating techniques,” says Maximilian Kückelhaus. “As a result, less tissue is destroyed and patients recover faster.” The specialists use the method for example on patients with breast cancer who need complex breast reconstructions, or after accidents in which patients need tissue transplants. With the aid of the robot and the robotic microscope, the microsurgeons can for example join up again the finest anatomical structures such as blood vessels, nerves or lymphatic vessels, which often have a diameter of only 0.3 millimeters.
During the operation, the robot – the so-called Symani Surgical System – adopts human hand movements via an electromagnetic field and joysticks. The robot carries out the operating surgeon’s movements, reduced in size by up to 20 times, via tiny instruments and, in doing so, completely eliminates any shaking present in (human) hands. A robotic microscope is connected to the operation robot, and this microscope shows the area being operated on via a so-called 3D Augmented Reality Headset with two high-resolution monitors. This headset contains a binoculars which are able to combine the real world with virtual information. In this way, the surgeon’s head movements can be recorded and transferred to the robot, making even complicated viewing angles possible on the area being operated on. In addition, the operating surgeon can access a variety of menus and perform functions with the robot without using his or her hands.
The new technology also has the advantage that operating surgeons can adopt a relaxed posture – whereas they otherwise have to perform operations in a strenuous posture over a period of several hours. “As we can now operate on patients in a remote fashion, we have much better ergonomics,” says Tobias Hirsch, who holds the Chair of Plastic Surgery at Münster University. “This in turn protects us from fatigue, and that means that our concentration can be maintained over a period of many hours. In initial studies involving the systems, before they were used in operations, we were already able to confirm the positive effects on the quality of operations and on ergonomics.” During training with students and established microsurgeons, the physicians were able to demonstrate that, while using the robotic system, the learning curve, the handling of the instruments, and the ergonomics all demonstrated an improvement over conventional operating techniques.
In the coming weeks and months, Maximilian Kückelhaus and Tobias Hirsch will be performing further operations and, in the process, collect data that they will be evaluating in scientific studies. Important issues to be addressed are, in particular, improvements to the quality of operations and to ergonomics. “Our hope is that with this new method we can not only perform operations with a greater degree of precision and safety – but also, in the case of the tiniest structures, go beyond limits imposed by the human body. Not having to be at the operating table can also mean that one day the operating surgeon will no longer have to be physically present. An expert might be able to perform special operations at any one of several locations – without having to travel and be there in person,” says Maximilian Kückelhaus, looking into the future.
Funding For the development of, and the clinical trials for, this new method of treatment, Maximilian Kückelhaus received funding from the European Union initiative entitled “Recovery Assistance for Cohesion and the Territories of Europe”.