The Bionic Man: Advancements in Medical Devices

The Bionic Man: Advancements in Medical Devices

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- Our program tonight is entitled The Bionic Man: Advancements in Medical Devices, and we could not have a better person to moderate our program, our moderator tonight is Robin Rasor who is the executive director of Duke's office of Licensing and Venture. Robin's full bio along with the bios of all of our speakers can be found on the event webpage, but we're not going to go into a lot of depth because we want to reserve time for the content of tonight's program But let me tell you a little bit about Robin, the office of License and Venture's mission is to partner with faculty, industry entrepreneurs and investors, to ensure that Duke's innovation reaches the marketplace, for the benefit of society and to create investments in future innovation. Robin oversees all functions of technology transfer that take place at Duke through the office of License and venture.,

she has worked previously with both University of Michigan and the Ohio State University, she has a Master's in Science and Genetics from the Ohio State University, and a BS in Bacteriology and Zoology from Ohio Wesleyan University, Robin is considered a national leader in university-based technology transfer, in short if you want to know how to get an idea from the research bench to the marketplace, Robin is your person. And we are so grateful that she is doing that every day at Duke University. Tonight, I'm pleased to turn the zoom screen and our program over to Robin Rasor, Robin. - As I'm sharing my screen after David's introduction I feel that I also need to point out as part of my hopefully you guys can see this now, is it showing up? David: Yes. Your PowerPoint is up.

- I should point out that I'm actually waiting list, Duke waiting list 1974, (laughing) at least Duke finally decided that I was worthwhile to be a part of the organization, when I came here about five years ago. What I want to do before we start was for the alumni, let you know a little bit about how we're doing in the whole tech transfer area, I mean very exciting things going on at Duke this is a little bit of numbers from our fiscal year 20, we do very well in terms of invention disclosures coming in that's our raw material, without our faculty who you're going to hear from tonight, we have nothing, it's really based on the inventive minds of our faculty resulting from the research and then we turn that into patent applications, issued patents, we do a lot of business in software and non patented kind of technologies. We're very fortunate that we do a fair number of agreements, last year we had $65 million in revenue, much of that came from drugs, this year we are going to top that number from some exciting things that are happening in this year. So we also spun out 17 new companies last year and it's not necessarily just the number of startups that are important to us, it's the quality of the companies, and the way we define quality is investible, do they get investment from Venture or elsewhere? Do they have acquisitions? Do they go public? And already in fiscal year 21 we've had some great successes. Two companies this year Actus and Phitonex were acquired, Actus is a gene therapy company based in the triangle area and was acquired by buyer for $4 billion, I have to say that periodically to believe it. Phitonex not so much but a good number for it, it was aquired by Thermo Fisher this year.

And many of you have heard about our two companies out of engineering that announced last week that they're going public through this Newfangled spec process, one is called IonQ which is a quantum computing company and the other is Evolve which is a security company, both of them out of the electrical engineering department, so very exciting times for Duke in all areas of technology seeing our technologies and our companies be successful going forward. So to that end, what I'd like to do is have our what we may do is one of our speakers is still in surgery, so what we might do is have two of our speakers introduce themselves quickly, and then I will turn the gavel over to Ken Gall as the first speaker, so maybe Ken and Shyni if you want to introduce yourselves, - Is he driving? - Yeah no problem, This is Ken I am not driving but I am in a car that's a long story, but I'm Ken Gall happy to be here and excited to present for you all, I'm a professor of Mechanical Engineering and I teach mechanical engineering, and I do research on 3D printing of biomaterials. - And then Shyni. - Hi I'm Shyni Varghese, I'm Professor of Biomedical Engineering, Mechanical Engineering and Orthopedic surgery, I just came to Duke four years back, before that I was UC San Diego. I work at

biometry, regional medicine, and smart devices. - So I'm going to now give the gavel to Ken and then I will be watching the chat room to see if I can keep track of any questions that you all might have. - Alright, thank you very much Robin, I'm in a car I'm not driving so don't worry, it's not like the surgeon who is on a zoom call doing surgery. Glad to be here, I'm going to talk a little bit about how we reconstruct the body through 3D printing, next slide please, so just real quickly I have a couple of disclosures, I do have equity ownership in a couple of these businesses, so we'll talk about university research, but how we translate that a little bit into a startup businesses and, most of the stuff I'll talk about today will be from a company called restor3d, which I founded while I was at Duke.

Next slide please, so you can play those videos, so if you don't know what 3D printing is, 3D printing is essentially a way to build a three-dimensional object from a fundamental kind of quantity, so the left is laser-based powder bed fusion of titanium, so you can build a three-dimensional object out of titanium directly from powder, and the right which you can also play, that's a laser-based polymer 3D printing process where you can build a polymer object, it looks like the polymer gets pulled right out of the liquid but it's a laser curing the plastic, and you can make very complex shapes for 3D printing, and then you can use these shapes to try to help make patient-specific implants. Next slide please, So the first question is, where might you use these types of things? And I'm just going to touch briefly on a bunch of these but you can actually use 3D printing to build things all over the body, and so we're working on things spanning all the way up from from airway to cervical spine, all the way down to foot and ankle. Next slide please, one of the real key things that we use 3D printing for is if you look at a standard metallic implant, it's a solid metal, and the problem with a solid metal is it has nowhere for the bone or the tissues to ingrow, and you'll see later that Shyni works on materials that try to get bone or other tissues to grow and attach to the things we put in, but with 3D printing we can make these implants highly porous and this porosity allows the implants to work in concert with bone and attach themselves to bone.

Next slide please, so for example you can see that if you have a very smooth surface this is just a example of a plot where you have a very smooth surface, the smooth surface will barely stick itself to bone, this would be like a K wire a very simple metal, if you move all the way up you get a factor of about 20 improvement with a porous structure and how well it sticks to bone. Next slide please, so just going to talk about couple of the things we do and then leave it at that, we do spinal reconstructions, I'm actually down here about to meet with a spine surgeon to talk about this, this is why I'm in a car I don't have a spot to be before I meet with the surgeon, but for example the old spinal fusion cages were just metal blocks that you'd go in, you'd have back pain, they'd take out the disc and they put this metal block in there and then try to get the two vertebrae of fuse together, we now can make a metal block that's porous and that porous structure helps the bone fuse those two vertebrae together in a way that actually incorporates with the bone rather than just puts a space between the bone. Next slide, you can do even more amazing things, so if you look at orthopedic oncology this is a really tough case where a very large tumor resection and the pelvis, so you see this young patient this is a 19 year old patient, lost half their pelvis and the problem is if you're going to lose half your pelvis like that you're going to have to either have an amputation in your leg or have a flail reconstruction, there's some other things you can try to do to salvage that, but especially for a very young active patient, they don't want that, what we've been able to do now with 3D printing, is you can take the contralateral scan of the other half of the pelvis and rebuild the pelvis with titanium, and this titanium will then has porosity and things to integrate itself with what's left of the pelvis, so this patient was a patient who probably wouldn't have walked and they were able to walk five days after surgery. Next slide please, Here's another one, trauma, this is why I'm not driving in the car right now, this is from an automobile accident, this is a person who when their car was hit from the side they lost the bottom part of their femur, it was shattered, but it was really kind of weird about this case was their knee joint was completely intact, so they didn't want to get a knee replacement, they wanted to just try to salvage just that part of the bone that was above, so we're able to 3D print us a device that actually made it exactly to the remaining parts of their knee and then they tailored itself right up to the rest of their tibia, and then has porosity all along that to try to get the bone to grow in there, and the idea is that implant and the patients they live in harmony then the implant is then integrated with the patient, and Shyni will talk a lot about the type of materials that go inside of these implants to help make that happen. Next slide, just a slide or two more, there's other issues in like lower extremities, there's a thing called Talar avascular necrosis, and this is where your talus dies, it sounds really random but it's just the bone and your tailus essentially is as lost blood supply, it dies, it disintegrates, and you've lost a bone in there and there's really not a good solution to this other, than amputation or losing a couple inches of height and some type of fusion, so we now can actually rebuild a tailus for the right half, if the patient lost by using the contralateral side on the left side of the patient and you can build this tailus that integrates with the bone on the bottom but then has a very smooth surface on the top, to interface with either a total joint or with the native bone on the tibia. Next slide please, this is also some other things you can start to think about other things, so you can design these 3D printed implants to actually give away in one way you want them to integrate with the body, so you designed them to integrate with that porosity, but you also can actually design them to release drugs and do things because you can put internal channels and reservoirs and things inside, this is an exciting project we had a Duke that we just licensed into our startup, where we have reservoirs filled with drugs so that if you have an infection or have something else that's going to happen or you think will happen, you can actually load these implants with drugs ahead of time.

Next slide, just a quick thing on some softer materials, we're looking at softer polymers those were all titanium and cobalt chrome, very high strength and metals, we're looking at areas like pulmonology where you need a very soft 3D printed scaffold, if someone has for example cancer and that's pressing into their airway, you need to be able to hold that open, and people traditionally use stents there we've been able to 3D print stents that actually fit exactly along that airway passage and then because of that, they match the anatomy and they don't move which is the biggest problem with stents in the airway. Next slide, we're also in the gynecology area, so looking at soft this is right now, we have a project with UPMC a hospital, and one of the leaders in pelvic organ prolapse so this is a really serious problem in female health, so you end with organs that are prolapse and then you need some type of mesh, there's been a bunch of litigations in this space because the meshes are very rigid and they tend to tear through the tissue, and those have stopped being used and we've been working on 3D printing something that's just as strong as the normal meshes that are used in pelvic organ prolapse but are much softer so they can actually cradle and hold the organs and things and not rip through the tissue, and we're able to do that by 3D printing complex structures in sort of a mesh fashion. The other problem with a normal mesh is that they normally closes so when the organs push on the mesh, the knitted mesh will close, but we can design it so that the 3D printed scaffold does not close and the pores stay open. Next slide please, I think I'm almost done here, last one I'll mention is just normal oncology in the breast area, we've been looking at can we replace? so if you think of lumpectomy where you have part of your breast tissue removed in a cancer situation, right now people put markers in there that are titanium and are very rigid, and so this not only fills the space but it provides a target for radiation. We can now 3D print in try to replace just the exact breast tissue that was taken out and then have that breast tissue replaced by something that's much softer and shaped exactly what was missing when a lumpectomy was performed.

Next slide, so I'll stop there, hopefully that was not too far off time I'm sorry I'm in a car, but hopefully it was still interesting for you all, and I'll pass this on to Shyni. Nandan is not next right? - I need to know, that is a hard task, anyway today I'm going to talk about some in the lab, I'll mainly be focused on creative platforms and approaches to advance health and some of them somewhat related to what Ken just mentioned. So the research in our lab, one area is regenerative medicine , that is where we are looking at how we can create formulations that promote cell function, for example if you want to create a bone ingrown, how we can recruit the cells, make them to differentiate into osteoblasts, that is the bone forming cells and take shape and function, so in this case you see cell organelle if you are using the stem cells to form a lean organ, and here this is a skeletal muscle and this is creating bone forming cells from stem cells.

We also use the same technology how the cells in back reduce these systems to understand the disease formation or the disease progression. In this case, we focus on cancer metastasis and fibrosis. And moving forward we create a number of therapeutic interventions, and in one case we looked at how we can change the issue environment to target fibrosis other phase is bone fracture healing and treating osteoporosis, and the cell transplantation for diabetes, or a liver, et cetera.

And another one is aging, how do the aging influence delayed fracture healing or in the case of a brain inflammation, for say most visits, and we also have an interest in creative smart materials and technologies like self-feeding hydrogels, soft robot organ on two platforms, et cetera. So in regenerative medicine space, we create tissue-specific biomimetic materials, then we use it as a platform or a tool to study the molecular mechanisms, identify new therapeutic targets, and see how we can support "in situ" tissue repair. I'm going to talk about mimicking bone tissues, so if you take a look at the bone tissue, you see a number of hierarchical structures and different aspects within the tissue, and we are envisioning mimicking the subcellular material and especially the calcium phosphate mineral.

So we have created the bio material, that mimic this calcium phosphate mineral produced in the bone tissue so you have calcium and phosphate, and we use this material to study bone health and disease and fracture healing, in fact, this study has led to creating a biomaterial which provides calcium and phosphate, so you have a cell that sees this calcium and phosphate, they activate a number of signaling pathways and finally get into something which is a bio molecule, that is adenosine, when you generate adenosine that promote bone formation by inhibiting fat formation. So we started looking at the possibility of using adenosine, or diagnosis as a therapy for bone fracture, healing and prevent fat formation, In fact, we have devised a biomaterial formulation to harness endogenous adenosine to heal bone tissue, and in fact this is the boronic acid in biomaterial, that complex with adenosine and form this complex, and this is the formulation, so someone has a fracture now so broken, so they get injected this biomaterial along with the therapy into the bone side and we can watch healing. In fact this technology is patented where we can either deliver the adenosine or seek adenosine in the bone.

This is animal studies this is the control where there is no therapy, and this is two different doses of adenosine, this is lower dose, and this is higher dose, and we are looking at the bone formation after a fracture, and you can see that with the therapeutic formation, when we use a therapeutic formulation we see higher bone formation, and this is also connected with the vascularization, so then we use this therapeutic formulation, we also see more blood supply to the injured side, recruiting stem cells, differentiating them into bone forming cells and improving in the healing process. Not only that it promote healing, it also mitigate fracture pain, in fact here we are looking at the ideal means of therapeutic formulation, and the other one is the control we are looking at the ability of the animal to walk or stand on their fractured leg and you see that they can put more weight when we have treated them with this injectable material formulation. We also now repurpose the same formulation to treat osteoporosis, osteoporosis is characterized by bone loss and the current therapy is Bisphosphonate-based drugs, they prevent the bone loss, they don't help forming the bone, so we started looking at creating a new drug in this space which can decrease the bone resorption, that means it can prevent the bone loss but also promote the bond formation, so you have an anabolic function not just preventing the catabolic function. So in this article, we have established this concept and then moving forward, we have created a Nanocarrier that has a bone targeting site, so when you inject them into the animal systemic injection they go and bind to the bone, then we have this drug loading arms which releases the drug and we have looked that the bone forming ability of this treatment. And here this is the control that means we have a healthy animal, then we have a osteoporotic animal then the osteoporotic animal treated with Nonocarrier, then this is the one where the osteoporotic animal treated with the drug formulation and I'm just going to show you that if you compare the four groups, you can see when you look at the bone mineral density, that the bone formation, you can see that the healthy and the treated one is very similar, similarly bone volume, and this other part we look at for bone formation, trabecular number, the other feature, trabecular thickness, connective tissue, these are a bunch parameters that we supposed to find out the bone formation, and you can see that when we have this therapeutic formulation that is very similar to the control, that is the healthy one. Now in the second we also, as I said we you have interest in creating smart materials, so one of our interests is creating self-repairing or self-healing biomaterials, so first we have created the self-healing hydrogels, in order to create the self-healing hydrogels, we have introduced with this dangling side-chain that allows us to take this hydrogel so this is how this is more like jelly jello, which we can make them heal or unheal, by just changing the pH, and here you can see this is the three hydrogen pieces that heal them together, this is a number of hydrogel pieces that you see are connected to each other or healed together, and in this case this is a three-piece hydrogel, they are hooked to each other and you can see that they're very strongly held so they can stick to each other, and in fact this video shows the self-healing material, so this is us that are generator, then we move into this solution which has low pH, and you can see that as soon as they stick to each other, they just heal so we can stretch them, in this case we are repeatedly stretching them and you can see that they stick to each other and they don't break, now using this type of engineering principles, we are creating self-healing lubricants, in this case, we made a hyaluronic acid based hydrogels to heal, so they can improve the retention within the joint and also we are investigating the ability of this self-healing lubricants to treat cartilage injury, and this is the material which can form a physical crossing and they will stick to each other, self healing, self-repairing and then they can restore them.

And this is the data showing that this is a healthy cartilage and this is the modified lubricant, and you can see that the better contraption when we treat them with the modified and this is the conventional. So as I said, we show all this data in mice and in fact this is a super mice, and I'm used (indistinct) if you have cancer and you are a mouse, we can take good care you the same way we treat the mouse. So we now start looking at creating humanized chips, so we can also look at how this therapeutics can be used to treat disease or more diseases, here we can create various organs on the human and we can connect to them, it's more like a level so we can move them out of them et cetera.

And this is vascularized liver tissue, this is a beating heart, so we can look at how the drug response, and this is a cancer where we are looking at the interactions, and this is lung-on-chip, which we are using to study SARS-CoV-2 infection, and also cancer metastasis into the liver, this is a blood-brain-barrier-on-chip where we are looking at neuroinflammation and brain aging. And finally my lab has some interest in my multi-functional soft robot, and this is a soft robot that was created to detect the temperature and also the acidity, and also otherwise contaminations. And I would just leave you with this, showing that the soft robot can move things and change their movement by taking a sharp return or taking a complex motion. With that, I would like to give all the credit to my students, they made me look way better by doing all these researches and with that I'm leaving, and thanks a lot for listening and I will give to Nandan. - Nandan you're up. - Okay sorry, thanks everyone can you hear me okay? Shyni, you're the only one on video.

Thanks everyone. Let me share my screen. Sorry I was in the OR late today here at Duke Hospital and I'm going to pull up my slides. So name is Nandan Lad, I'm Vice Chair of Innovation and Department of Neurosurgery here at Duke, and also have an appointment in mechanical engineering, and I wanted to share my perspective on the bionic man in terms of innovations in functional neurosurgery which is my area of sub-specialization. And there's a lot to cover in the 10 minutes we have, so I just wanted to share a few of the procedures that we do routinely that really serve to modify or enhance the function of the nervous system, hence the name functional neurosurgery. And so deep brain stimulation is one procedure that you may have heard of or DBS for short, it's most commonly used for Parkinson's disease, essential tremor and dystonia are the three main FDA approved indications currently.

But as our understanding of the brain circuitry expands, and as imaging improves we can start to see these fiber tracks or circuits and potentially modulate how those circuits work and how they can be strengthened over time in the case of neurodegenerative diseases like Parkinson's. And so the brain is an amazing organ, I'm sure you've seen pictures, but it's amazing to see upfront in person and the brainstem is the core reptilian brain if you will, but has all the core functions that we rely on a daily basis, and this is a human brainstem taht we dissected here in the anatomy lab? And so this is the view that we're starting to see, so rather than just as a static structure it's a bundle of these different circuits or connections between one area of the brain and the other, and as we start to understand how these circuits work, where they connect from one region to another, I think the ability to have targeted surgical or interventional procedures that modulate these circuits and enhance our function or restore our function, after a stroke with Alzheimer's disease, with a lot of these things that have been relegated to neurology, it's my hope that over the next 20, 30 years we'll have solutions for many of these conditions and that Duke will play a big part of it. So in terms of circuitry, this is a simple circuit called a tremor circuit, and so this is a procedure I did actually one just earlier today, is a deep brain stimulator for essential tremor, and it's usually a benign condition where patients have worsening tremor over time, certainly it's medically managed for many years but at some point it becomes very disabling to their daily quality of life. And I think we have some videos and the circuit here is the dentato-rubro-thalamic tract the DRT tract for short, that we're modulating with the stimulator, and so this is how we're starting to view the circuitry that we're starting to selectively stimulate and intervene on as you can see here, so it's a deep in the brain hence the name deep brain stimulator, so eight centimeters deep in the brain and we're targeting a very small structure usually on the order of three to five millimeters, and so that's the precision, every millimeter matters that we need when we're targeting these fine fiber tracks, obviously we want to maximize the benefit while minimizing the side effects.

And so this is a zoomed in version of what that looks like at a higher resolution, and so the proximity of the electrode to the DRT tract in this case for a central tremor directly correlates with efficacy in terms of improvement of tremor. This is a patient and you can see here that his tremor there on the left part of your screen is quite disabling in terms of his day-to-day functions and had been medically managed for many years, and then underwent deep brain stimulation. - Can you put both hands out straight in front of you? With your right hand can you slowly bring it up to your mouth? - And some of you may have seen videos like this but some of you may not have, - How about with your left hand, can you put that straight up? - And I think it just really demonstrates the dramatic impact an existing procedure can do in functional neurosurgery. - With your right hand, can you slowly bring it up to your mouth? - So he's rock solid now, and this was only a month post-op he's now I think five years post-op and continuing to do great. And so some of the new directions, if you will in DBS and navigation is current steering, so for the last 20 plus years that DBS has been around, it's just been a ball of energy, if you will, a sphere of energy that is emitted from that electrode, and now we have the ability to contour that field, so if you want to direct the current North or East or West or South and have different shapes so that you're stimulating some circuits while avoiding other circuits, that's not possible, and that's a relatively new innovation just in the last one to two years, and now it's become quickly the standard of care in this area of neurosurgery.

And so structural connectomics, this is our way of saying if the globe is the human brain and we're interested in going to Duke university, it's similar to that tremor circuit, that's a six millimeter target that we're trying to hit with a sub-millimeter precision, but there's a lot of other structures around Duke university that are really important in terms of what we're stimulating and what connections we're strengthening. And functional connectomics rather than structural connectomics is that each of these just like all of us, we're all connected, each part of the brain is connected, and you can look at it whether it be the rail map of North Carolina, or the nonstop flights from RDU, however, you'd like to think about it but by modulating one part of that circuit you're affecting many other parts of the circuit as well. And so that's something we're just starting to understand better as imaging has improved and looking at how that circuit modulation occurs.

One of the clinical trials will be a part of here at Duke is deeper in stimulation for Alzheimer's disease, and in that case, it's the memory circuit and we're stimulating in the front of the brain and the fornix and that's modulating the hippocampus which is at the tail end of that circuit, so exciting times for sure. This is just another view of that, this is a one cubic millimeter of tissue of brain tissue showing how when you expand in on that just like the globe analogy I gave, there's 50,000 neurons and a billion plus synapses that are concentrated in that one cubic millimeter of tissue, and so I think the ability of current steering is one step forward but still as you look at the broader view of what that circuit looks like, there's a lot to learn and I'm excited about the coming years that we can contribute to this. The spinal cord and peripheral nervous system is another broad area of functional neurosurgery in terms of how he modulates that, and to be very succinct about it there's 31 different nerve roots, each of these are connections as you go from the brain to the rest of the body, and each of these cables is something that we rely on, and certainly we realize when something goes awry whether that's sciatica or trigeminal neuralgia which is another surgery I was just doing today. And so each of these nerves can be affected and any one of them can lead to debilitating pain or other serious neurologic conditions. And so one common procedure we do is spinal cord stimulation which in the spirit of the bionic man is is also an implanted device essentially instead of a brain pacemaker it's a pain pacemaker that's implanted over the spinal cord, this is a very simple type of device with two electrodes connected to very similar technology as the deep brain stimulator and cardiac pacemakers.

And the main innovations in this area have been around software, the frequency of stimulation and expanding the types of indications that can be treated with spinal cord stimulation. Again, our understanding of the spinal cord anatomy is improving I showed you those nice images of the brain circuitry, we're not quite there yet in terms of spinal cord circuitry. We still have these sort of cartoon diagrams, of the different regions of the spinal cord but within each of these regions there's tens of thousands of neurons that are critical and having that level of specificity, we just don't have yet, but I think that we will be moving in that direction over the coming years. One step in that direction is using the type of energy that is selected for certain types of neurons and stimulating that way, so stimulating neurons in the dorsal horn as shown in the middle there with a higher frequency stimulation versus lower frequency is more the dorsal part of the spinal cord in the dorsal columns and then combining those frequencies for different types of pain conditions, and so these are three big clinical trials.

We've been a part of painful diabetic neuropathy, non-surgical refractory back pain and complex regional pain syndrome, that I think will rapidly expand the indications and the patients that can benefit from spinal cord stimulation, in terms of where this field is going closed loop spinal cord stimulation is a relatively new in the past year where given we change body positions from sitting to standing and how we regulate what is stimulated and how it's stimulated is now possible with that closed loop feedback. And then finally, the last procedure I'll share is something called the dorsal root entry zone or DREZ procedure, It was pioneered here at Duke back in the seventies and it's something that's still we get referrals from all over the country for targeted ablations, when that circuit goes awry. So rather than implanting a device like in the first two examples of deep brain stimulation and spinal cord stimulation this like the fuse box in your house and sort of resetting that fuse box very specifically where that nerve has been damaged, this patient had a brachial plexus avulsion which is highlighted there in the white where the nerve root is actually severed from the spinal cord.

It's usually from a high-velocity accident like a motorcycle accident or a speed boat or something similar, for the patients that treated recently and, this is what the spinal cord looks like and maybe this isn't for everyone, but, you know I think seeing the anatomy in real life under the microscope is always amazing. So on the one side is the nerve roots shown by the suction and on the side in the orange is where they're missing, and you can see that opening there where that adult segment is. and we interrupt that with a targeted lesion, and where this is going is again high resolution imaging, and so this is the highest resolution map of the spinal cord that we worked with Dr. Allan Johnson here at Duke to build, so it's one micron resolution of the human spinal cord and something that again will be a step in that direction of imaging more specifically what those fiber tracks and connections are between one area and another. And so with that the future is bright, Everyone hears about Neuralink and Elon Musk, and a lot of people ask me, when is this happening? And I think it it'll happen soon in our lifetime but there's a lot of other types of brain machine interfaces, like deep brain stimulation or spinal cord, computer interfaces like spinal cord stimulation that we do every day, and so Neuralink is certainly a very exciting and has a another order of magnitude of precision using robotic techniques and very thin filaments to help people that currently can't move and are in wheelchairs to communicate, and I think that's really exciting and I'm looking forward to seeing how that unfolds.

So with that thanks for your time and attention. - So I think we'll do, and thank you to all of you who have posted questions, and we're going to try and ask a couple of them to each person. So first with Ken, I'm just going to ask you two questions and you're going to answer them however you want. The first one is, if you have a MRSA Infection that has had trouble with orthopedic hardware, is there any implant that can avoid exaggerating the infection? And then the second one is, are there major changes in the rehab process or functional outcomes after the types of surgical interventions that you've demonstrated? - Yeah. Thank you. As far as the first question the answer is yes, there's a lot of work being done on coatings for orthopedic implants that or other implants that would try to really prevent infections or reduce the severity of them, and then we are working on things where we can use the implant and the open spaces in the implant to actually store drugs that may treat infection, so this is a big issue. Implants do make infections worse often if you have a type of infection, so that is something that's happening.

And then the second one is on the rehab protocol and I think that's behind right now. So to be honest I think we're even I had surgery on my arm two years ago, for example and the rehab protocols even for that are behind a little bit the times, and I think that they're probably behind the times for these types of newer reconstructions, so that's a great area of work to be done in my view, it's a great question. Thank you - Next for Shyni, How far out do you see some of these bone growth technologies before they'll start being used in the clinic or in patients? - They have mostly in animal studies which is very effective, so they had a lot of small animal in studies like mice, so maybe go to a large animal before we go to a clinical trial.

- And then a bit of a corollary how much does the chip based technology accelerate the development of some of these new therapies? - The drug discovery space the organ on a chip is going to make a big difference, in fact we have started using some of them, it doesn't replace the animal studies but it will build the gap between the cell cultures with the animal studies. So you can get to whether the drug works in a human specific condition. - Okay. Thanks. And then Nandan, a couple, has any deep brain stimulation been done with respect to primary progressive aphasia? And then the second is, are there any prospective use of DBS to treat depression? - Yeah, no great questions, so I mean language is critical and amazing and I think our understanding of syntax, of consonants, vowels, how we put words together is evolving rapidly, so some of our colleagues across the country as well as here at Duke, our first patient today participated in a research study actually in the operating room, looking at different syntax and putting together consonants and vowels, and so it's a step in the right direction of understanding how the brain processes those components of language to help patients with problems like aphasia to communicate using brain computer interfaces. The second question around depression, there have been several large clinical trials actually probably about 10 years ago now, looking at medication refractory depression, the challenge is I think, twofold so they didn't meet their primary endpoint is the short version, but the longer version is that imaging is not as good as it was today, the targeting wasn't standardized in terms of sub-millimeter precision, like I showed you, if you're off by a couple millimeters, that's a big deal and you're not stimulating the circuit that you think you're stimulating.

And so there's a lot of variability and heterogeneity and how people were placing those electrodes and what they thought they were stimulating versus what they were actually stimulating when they went back and looked at the imaging, and then I think also the patients that get selected for large trials like that for depression are challenging, they've failed five medications, they failed DCT and they expect their primary endpoint to meet efficacy at three months, and so I think that's a tall order for any therapy, and so having a longer time or a time horizon in terms of what the therapy can do over time or expanding that to patients maybe earlier in the disease course like they're doing with Alzheimer's disease earlier mild cognitive impairment, are the primary patients that are being enrolled for that study. - Great back to Ken in some of these typical well, I don't know, a lot of your stuff is not typical, how long does the printing, can you walk them through the from the beginning to the end, the printing process, how long does that take? - So it takes a couple hours to load the printer up and get it all ready to go for we'll take a metal implant which is the longer couple of hours sometimes to load and unload all the processing, the actual print if it was a full pelvis that would probably take a day or two, if it was just a whole bunch of small implants or let's say a replacement for a part of your finger or something like a scaphoid, that would probably take a hour or two, and then the instruments print in about 12 hours. So it's a longer process but you can run them all in parallel, so that it's a very low cost process because you don't have to be sitting there doing anything it's just happening. - So no one has to can they be run overnight, does someone have to watch the machine at all times or - They do not.

They're all now monitor by web so you can watch them on webcam and stuff, so to make sure it's working but they're all instrumented, it just happens. it's just the removal of the implants takes some time, but that's it. - Okay for those of you alumni who haven't been back in a while, there's this wonderful facility at Duke called the Co-Lab that has a whole bunch of 3D printing machines and, the students can send stuff from their dorms, it's a great place to visit if you haven't seen it. So some of them - Robin, if you don't mind I'll say one thing, and more than welcome to come visit the restorative facility too which is also is close to Duke's campus, so the Co-Lab is an awesome place to visit, and we can also share the metal printers restored. - Yeah, it's really an interesting place. I have a question here, but not even sure who it's for, it says retinol or optic nerve machine interfaces for sight restoration, who is this for? - My wife is an ophthalmologist here at Duke, so she tells me a little bit about the innovations happening in that area of the world, and retina is their specialty actually, so there have been different retinal prosthetics for retinitis, pigmentosa and other conditions, there are also things looking at stimulating the occipital cortex in inpatients that to try to restore some, hand motion and basic vision, I think there, those are still in clinical trials, and the cost and the time required is a lot, but it's important for patients that need to recover vision but what's still in trials.

- And then we have and Shyni this one's a pretty detailed one. Do you use a control group that consumes a similar quantity of boron and adenosine? - Yes, we have multiple controls so we use either detailed formulation or partial formulation, so in short yes. - And then I guess in the little bit of time we have left do any of you want to comment about I guess I would say I've seen in the last five years that I've been at Duke, I mean, one of the wonderful things about Duke is that we're still while we're a big university from a health system perspective we're still a small university in terms of location. And can you talk a little bit about how you all have met each other or the interactions how easy it is to walk across campus from engineering to medicine or if there's things about Duke that make it special to you in your innovation process? Anybody who wants to answer? - I can say something quick and then let the others, I moved from Georgia Tech to Duke and I work with both Shyni and Nandan some, there's two things that are important for me, the proximity of the people there at the hospital has been just absolutely incredible, so that has really helped, we can get together for meetings, obviously that's been a little different the past year but that has been incredible, but that's probably a 10% factor, the 90% is that the surgeons are just absolute innovators, I mean, it's been pretty amazing to work with them and really they want to pioneer areas and not take excessive risk but really just go after the newest technologies that can really make a difference with patients, and I've just not seen that anywhere else that I've been. And there's a pretty good tech transfer office person too, so that's been, that's been helpful. - Nandan and I mean as one of the surgeons I think the other advantage is you can walk, one of the things I love about walking on campus is seeing docs walking across over to engineering and vice versa, it's just really coming from a much bigger university, University of Michigan that didn't happen, you had to drive everywhere and just watching those kinds of people just walking back and forth whether or not you ever get off out of the OR to actually walk across the street and see Ken is another issue, but - I do.

So yeah my background, I was at Stanford before coming to Duke 10 years ago and very similar in terms of strong universities, strong medical center in close proximity, and that's one of the things that attracted me to come to Durham. And like Ken said, it's very collaborative engineering is very strong that collaboration helps move projects forward, we work with Ken on a bunch of different projects and in the medical device space, and I think you've been a big asset in terms of changing the mindset, honestly to a progressive technology forward, how do we get these things to patients, which is the ultimate goal of all of these innovations? - Well and Shyni you're the newest person here, I don't know if you want to make any comments about how you've seen it since you arrived. - I agree with both Ken and Nandan.

- And then one last question, I think that I'm going to get the hook. Do any of you want to comment on how the advancements in gene and cell therapy impact, the future of your areas of research for the alumni on here, you should know that we are developing and are very strong in both gene therapy and cell therapy, over the past couple of years have recruited a number of people, we have some of the top minds in both of those areas and as well as in CRISPR, so there's a lot going on campus in all of these areas, so it's exciting time, and for tech transfer person, that's really exciting cause that's also hot areas. And so companies in Venture continue to come to Duke because of our faculty, but I don't know if you want to comment on how you're using any of or interacting with any of these researchers in your own research.

Shyni? - Some stuff that I've been mainly for looking at the cells at the drug store, so can you transplant the cells, for example can you transplant pig cells into human? and let them insulin on a facto nine in the case of hemophilia. So they look at it how that can be possible. So in that case the collaborate with physicians seeing the patients.

(indistinct) - So David are you taking over now? - Fantastic. Well I just wow. I am encouraged, inspired, a little bit terrified about everything that is possible but maybe that's because I watched too many Sci-fi movies but it is just amazing to hear what is happening. I want to thank Robin Rasor, and each of our panelists for an amazing Duke night, it is such a privilege to kind of step back into the classroom and to learn, and to be inspired and just to be so proud of everything that's happened at Duke. I think we can safely say that every day new possibilities are emerging and Duke has an active hand in many of those extraordinary possibilities.

I also want to share with you, there are still over a dozen sessions like this that are part of the Forever Learning Institute coming up yet this spring I'm going to put in the chat two web links. One is for the course description of all the spring courses for their Forever Learning Institute. There's also a link to the Lifetime Learning YouTube page where ultimately all of these programs are shared with our alumni and you can come back and listen to them later.

The next two sessions in advancing the health and wellness track look equally amazing. We have advancing healthcare with technology. That's going to be hosted by Pratt Dean Ravi Bellamkonda, who is just amazing. And that's going to be on April 16th. We're also going to revisit a book, we've talked about a bit with alumni before which is entitled, "Black Man in a White Coat" with the author faculty member and Duke alum, David Tweedy, he's going to be in conversation with the chancellor of Duke health system, Eugene Washington, and that is on May 25th. And also stay tuned in July.

we'll be announcing the entire fall lineup, so we'll be just like being back at Duke and signing up for classes, you'll be able to sign up for an incredible fall series of programs, which will be both inspiring, and I think you will enjoy continuing to learn. and that is our goal that we set up an opportunity for a lifetime of learning for our alumni. I am so glad you could join us tonight, I want to once again, thank our amazing panel, we look forward to seeing you at the next Forever Learning Institute program and to the next Duke alumni event that we have planned for you coming up in the next days and weeks.

I hope that you stay safe. You have a great evening and I want to wish you a good night. Thank you so much.

2021-04-02 22:42

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