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Research Benno Hendriks

It’s important during cancer operations that the tumour is completely removed. In order to do this as accurately as possible, surgeons base their operation plan on images that were made during the diagnostic phase with imaging techniques. Surgeons then have to largely rely on their senses during the operation. According to Benno Hendriks, part-time professor of optics for minimally invasive instruments at TU Delft and research fellow at Philips Research in Eindhoven, we can do better. All too often, a piece of affected tissue is left behind or healthy tissue is damaged by the operation. This can lead to repeat surgery, extra treatments and worse patient outcomes. More feedback during the operation could change that. How? According to Hendriks by adding optical feedback in surgical instruments. Put simply, it involves recognising tissue with the aid of light. Different molecules absorb and emit light at different wavelengths. We see that as colour, which is why blood is red, for example, and fatty tissue yellow. ‘With spectroscopy we look at these colours of the light. It enables us to distinguish more accurately than we can with our eyes,’ says Hendriks. Biopsy needles made from optical fibre technology He applied that principle in recent years by providing biopsy needles with optical feedback. ‘When you take a tissue sample from a lung, for example, it inevitably moves during the procedure as a result of breathing,’ Hendriks explains. ‘So no matter how precise your X-ray or MRI images are, there’s always the risk of imprecision during the placement of the needle.’ To solve that dilemma, Hendriks and his colleagues equipped biopsy needles with optical fibre technology. ‘The ends of the optical fibre are placed in the tip of the needle. One optical fibre functions as a light source, which it shines into the tissue; another optical fibre collects the light that went through the tissue and that signal is transmitted to a detector,’ he explains. This makes it possible to read the tissue and determine whether it’s normal or abnormal tissue. Of course, it has to first be clear how to distinguish between normal and abnormal tissue. A great deal of research went into that. ‘I measured all kinds of tissues in different situations in hospitals,’ Hendriks says. ‘To begin with at the pathology department with tissues taken from patients.’ He worked together with the Netherlands Cancer Institute for this, for example. Armed with knowledge about the tissue, he subsequently began to incorporate the technology into the biopsy needles. ‘That’s quite complex, because it’s a moving system. The last step in the development process is to then validate your instrument in practice.’ Introduction into the market Once all these steps in the development process have been taken it’s up to the business unit – of Philips or another company – to assess whether it’s the right time to introduce the innovation into the market. Money plays a role of course. Hendriks also conducted research on the possibilities of using a similar system for nerve tissue recognition during local anaesthesia, for example. ‘During local anaesthesia you have to place the needle very close to the nerve. If you’re too far away from it, it won’t work. If you do it in the wrong place, you can damage the nerve,’ he says. Spectroscopic imaging of the nerve tissue would help. ‘But anaesthesia needles are quite inexpensive tools. There is always a limit to what the technology is allowed to cost. If an anaesthesia needle or a biopsy needle becomes too expensive as a result of the innovation, then it won’t be used after all.’ Smart surgical knife Though it may seem as if new technology equates additional costs, in reality it can save a great deal in medical and social costs. Another of Hendriks’ ideas is to adapt the popular electric surgical knife, which is used to cauterise tissue. ‘You could make a knife like that smart, so that the tip of the knife recognises the tissue before you start cutting,’ he explains. ‘So it only cuts when you press on the button, and that can easily be integrated into the feedback loop. If it gives you a signal telling you to stop, then the knife stops immediately.’ However, you cannot take the spectroscopic tissue recognition that’s used in biopsy needles, for example, and use it in exactly the same way in a surgical knife. ‘This is much more complex, because when you cut, you also alter the tissue a bit in the vicinity of the knife. It’s similar to meat that turns brown when you fry it. In other words, it affects the optical signals that you’re receiving.’ ‘We therefore have to first conduct all kinds of research on the interaction of the knife with the tissue,’ he continues. Back to square one, in other words, and to the pathology lab. And that’s just the beginning, because how do you then integrate the feedback into the knife with precision and simultaneously retain the other functions? Surgeons have to be involved in this research too. ‘How exactly do you use the knife? When is it useful for a surgeon to receive feedback? And then there are many other questions that will need answering in the coming years,’ Hendriks says. The surgical knife is only one example. ‘Many other instruments are used during operations, such as sutures and devices to make connections between intestines. You could make all of these smarter and thus prevent all kinds of complications.’ Innovation & cooperation Integration and cooperation are indispensable factors in this. ‘The magic word for innovation in the medical world is “simple”. It has to be easy to use and intuitive,’ Hendriks says. ‘That’s also the approach at Philips: if you take your innovations to a hospital, make sure that they aren’t a bunch of loose components but a total concept.’ According to Hendriks it’s the concerted effort of all parties that determines an innovation’s success. ‘Part of the solution lies with companies such as Philips, part with TU Delft and another part with the hospital. So you have to start working together early in the process.’ He believes a good example is the coronary catheterisation lab, where diagnoses are made but also where stents are used to treat narrow arteries and heart valves are even replaced through the groin. ‘Something that used to require an open heart operation can now be done with an intervention that takes a couple of minutes. Once you’re done on the table, you can go home, so to speak,’ says Hendriks. ‘That’s the power of the integration of systems such as imaging, navigation and instruments. As a result, something highly complex has been made simple.’ Personal motivation With his new chair, many of the components that need to be integrated in the operating room are coming together. ‘TU Delft, for example, is strong in building steerable instruments, such as those used in keyhole surgery. Here we are also looking at the workflow in operating rooms and how to train physicians to use new systems.’ Hendriks sees great opportunities ahead. ‘In most operations today, it all comes down to the skill of the surgeon. If you can manage to take image guidance from the diagnostic stage to the operating room, then you’ve already taken a big step forward. And if you can combine that with sensing technology and feedback, you’ll advance the entire field. That’s my goal.’ ‘As a research fellow at Philips I have the opportunity to explore new directions and delve into my subject more extensively,’ Hendriks says. ‘Research at a company does have a different focus: a company opts for things that have potential today. A university has the liberty to look at things in the long term.’ He sees his dual role as an opportunity to bring the two closer together. ‘You can’t do it on your own. As a company, you can’t test all of the new directions that will become interesting in a few years. On the other hand, it’s of little use for a university to invest in potential solutions just to discover years later that no one wants to use it in practice. I want to help to bridge these two situations.’ Benno Hendriks

3D-printing and origami

Image reproduced by permission of Shahram Janbaz from Materials Horizons, 2016 DOI: 10.1039/C6MH00195E The latest bone prosthetics are 3D-printed. They are custom made and have pores which are invaded by bone cells. Yet, materials scientist Amir Zadpoor believes the implants can become even more effective - by using origami of biomaterials. The surgeon steps back for a moment. Gently a scanner spins over and around the patient on the operating table. Equipment in the corner awakens and spits out a peculiar flat sheet with gaps and strips. It falls into a jar filled with liquid and starts to swell and fold. After a few minutes, it perfectly fits the cavity the surgeon just had to make to remove a large bone tumour. The prosthetic is quickly clicked in place. This is how Amir Zadpoor, materials scientist at Delft University of Technology, envisions the future of 3D-printed implants. “The prosthetics will consist of a layered, porous material that easily adheres to natural bone”, he predicts. “The pores will be quickly occupied by new, healthy bone. Within months the implant will be almost indistinguishable from real bone, and will last a lifetime.” It’s a long way off, acknowledges Zadpoor. But also a logic next step in what is happening in the clinic today. Custom made 3D-printed prosthetics are already rescuing patients own bone. Sander Dijkstra, orthopaedic surgeon at Leiden University Medical Center: “Just a few days ago, one of my patients told me that he had been jogging again. That’s wonderful and very rewarding.” Before the introduction of 3D-printed implants Dijkstra always had to remove the total knee joint of people with a large malignant tumour in the femur. “Especially for young people it is a terrible prospect to never be able to run again.” Porous The 3D-printed prosthetics that Dijkstra currently uses are partially porous. That is the result of research by materials scientists such as Zadpoor: “We helped developing 3D-printing techniques for porous, yet strong implants. Because of the porosity, the surface of these implants is many times larger, which means that the antibacterial surface coating is many times more effective. Moreover, bone cells can settle down in the pores. That provides a better integration with the body and strengthens the implant.” All a very welcome improvements, finds Dijkstra. Currently, one in every seven implants needs to be replaced. “Implants may loosen and wear out. Young patients in particular run the risk of having a prosthetic replaced later in their life.” Additively manufactured (3D printed) porous biomaterials aimed for bone tissue regeneration manufactured at the Additive Manufacturing Laboratory, TU Delft (Medical Delta © de Beeldredacteur). When 3D-printed prosthetics last longer, why isn’t every implant printed? Zadpoor: “At the moment, these implants are still relatively expensive because their manufacturing involves many specialists. I expect costs to decline substantially over the coming years. After that, standard implants could indeed also be printed.” Still, Zadpoor doesn’t expect to see 3D-printed hip replacements on the market any time soon. “Those kinds of implants are extremely optimized products causing very few complications. To replace them, benefits need to be large and proved conclusively. That requires long-term research.” Schoulder blade At the moment Dijkstra places a 3D-printed prosthetic about once every four months. It is certainly no standard procedure. The orthopaedist is one of the pioneers. The 3D-printer doesn’t stand in the surgery yet, but at a specialized company called Implantcast (Germany). Dijkstra: “We make a CT-scan of the affected bone and decide which part needs to be removed. Using specialized software, we design a prosthesis that will perfectly fit on the remaining bone above the knee. The top is attached to a standard pin which is anchored to the healthy upper part of the femur.” The whole procedure from design to surgery takes about seven weeks. Doctors and engineers deliberate at several stages on the optimal design of the implant. In the meantime, the patient receives chemo therapy to treat possible metastases. The group of patients that qualify for a 3D-prosthetic is small: young people with severe bone tumours. And the technique is only used when standard implants provide no satisfactory solution. Dijkstra has also replaced half a shoulder blade and part of a pelvis – bones for which no standard prosthetics exist. Dijkstra: “A new product always comes with a risk. An unknown, unexpected weakness may present itself over time. As a physician, I’m well aware of that. We first treat patients that will gain the most by a 3D-printed implant and follow them closely over a longer period in time.” Also a copy is manufactured of every 3D-printed implant Dijkstra places. Scientists at the Delft laboratories examine if it could be improved further. Origami Zadpoor wants to fuse 3D-printed prosthetics even further with the body. To achieve that, the material scientist wants the ‘impossible’. For about ten years, it’s evident that a particular surface pattern on implants can stimulate the growth of bone cells. Probably, the cells like to attach to this particular surface because it resembles natural bone well. Zadpoor wants to incorporate this pattern in the pores of 3D-printed implants. However, it’s a nanopattern: ridges with a height of only a few thousands of a millimetre. Zadpoor: “Such a nanotopography can be created with techniques from the semiconductor industry, but only on flat surfaces. The technique is not compatible with 3D-printing.” Zadpoor wants to resolve this problem with ‘self-folding materials’. “Think of origami”, Zadpoor starts his explanation. “You start with a flat piece of paper, but end up with a highly complex folded form.” The idea is to print flat structures and apply the desired nanopattern onto them. Then a folding trick applied. The printed material is made from various layers of passive and active polymers. These materials shrink or swell when the temperature rises, when they become moist or when light is falling upon them. Zadpoor: “We combine the metamaterials in such a way that flat objects spontaneously fold themselves or roll up.” Self-folding origami Millions The European Union granted Zadpoors idea in 2015 with 1.5 million euro (ERC-grant). Recently, the first visible results were delivered: a staircase-like shape that turns into a DNA-like structure under water and a cellular structure that transforms into a patterned shape. But how do these origami materials result in the porous 3D-printed implants with nanotopograhy that will help patients? Zadpoor: “This is fundamental research. We have now provided proof-of-principle in how 2D-materials can fold themselves into 3D-structures. It will take a lot of further experiments to finally create the durable implants we want.” Self-twisting of DNA-inspired constructs To reach that final goal, Zadpoor cooperates with several hospitals in and outside the region and with large and small businesses. He also participates in large, international research projects such as the recently started PRosPERoS ( PRinting PERsonalized orthopaedic implantS ) with a budget of nearly five million euros. Zadpoor's laboratory in Delft has become an important hub in the development of new biomaterials. Yet, he could easily have worked at SpaceX or Boeing. Zadpoor holds a PhD-degree in Aerospace Engineering. “Six years ago, I made a well-considered decision to switch from aircraft materials to biomaterials. After all, nothing is more rewarding than to help curing people.” Read the press release here . Nederlandse media Door origami geïnspireerd botherstel Nemo Kennislink, 25 oktober 2016 Origami en 3D-printen voor zelfbouwende materialen De Ingenieur, 22 oktober 2016 TU Delft gebruikt origami voor 3d-objecten met oppervlaktepatroon Bits & Chips, 24 oktober 2016 TU Delft combineert 3D-printen met orgimami-technieken voor implantaten ICT & Health, 1 november 2016 3D-printen en origami bij ontwikkeling zelfvouwende medische implantaten (video), 23 oktober 2016 Zelfvouwend origami-botweefsel uit de 3D-printer BNR radio, 24 oktober 2016 Zelfvouwende medische implantaten door 3D-printen en origami Nano House, 30 oktober 2016 Kennis van Nu, 2 maart 2017: International media 3-D printing and origami techniques combined in development of self-folding medical implants, 21 oktober 2016 TU Delft researchers pioneer self-folding medical implants using 3D printing and origami techniques, 24 oktober 2016 3D Printing and Origami Could Yield Self-Folding Medical Implants, 24 oktober 2016 Self folding medical implants 3D PRINTING & ORIGAMI TECHNIQUES FOR MEDICAL IMPLANTS, 2-11-2016 3d-printing and origami techniques combined development self folding medical implants Bio Focus: Nanopatterned self-folding origami may open up new possibilities in tissue engineering MRS Bulletin, 28 november 2016 Bio Focus: Nanopatterned self-folding origami may open up new possibilities in tissue engineering MRS Bulletin, 7 november 2016 Shape Memory Polymers to Create Origami-like Biomplants EdgyLabs, 8 november 2016 3D printanje i origami tehnike u kombinaciji razvoja samosklopivih medicinskih implantata, 6 november 2016 TU Delft researchers develop self-twisting of DNA-inspired constructs (VIDEO), 26 oktober 2016 Amir Zadpoor
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