[Music] today on the future of everything the future of 3d printing for health well the last few decades have witnessed a revolution in the field of 3d printing now this is the technology that allows us to create 3d objects based on a digital model that starts out in a computer these usually work by having soft materials of some kind that can be deposited or formed often layer by layer and as that material hardens it can create a variety of shapes including complex geometries that include holes and support structures and really quite complex 3d structures these 3d printing technologies have advanced with the introduction of more diverse materials more precision in the creation of these objects and we have seen them used to create a wide variety of things including rapid prototypes of new products from spoons to complex uh devices with multiple parts they can often be used to replace difficult to find parts for machines they've even been reported to create working guns but that's not what we're talking about today we're talking about something we don't usually think about which is how can these 3d printed objects become critical in healthcare in fact 3d printing has promise in providing new ways to deliver therapies including medications and vaccines professor joseph de simone is a professor of radiology chemical engineering chemistry and operations information technology at stanford university he works on the development and use of 3d printing for applications in health joe how has the evolution and improvement in 3d printing created opportunities for health oh first of all russ it's great to be here with you uh thank you so what's happened you know 3d printing has been historically a prototyping technology and it's allowed an amazing um ability for designers in a lot of different fields to design new products the big transition that's underway is that 3d printing the the technology itself the printers the hardware uh the materials the software has gotten to the point where 3d printing can now transition to manufacturing and scalability uh and when you start thinking about one's anatomy the bespoke nature of perfectly fitting products uh and scaling at the same time is a really interesting intersection for the field great so i know that you've been very involved in something called clip technology for 3d printing and you've been involved in companies and i think this is a basis for a lot of what you do can you just give us a high level description of how this technology works and maybe some of the sense of its capabilities and where the frontiers are yeah so 3d printing was invented in the 1980s and it emerged out of the discipline of mechanical engineering you know we're one very precisely deposited layer by layer films you know like a like a xerox machine but you do it over and over again pretty soon that it gets thicker and thicker and thicker and that's what 3d printing was right and it's really been 2d printing over and over and over again because you're kind of layering these printouts so to speak on top of one another to create the shapes that's right more and people are probably more familiar with like a makerbot kind of product which is like a hot melt glue gun rastering across the surface right and my team and i came at this from a chemistry point of view and a physics point of view and you know chemists like to grow crystals and we were thinking about wouldn't it be great if we could grow these products continuously and we invented a method uh that uses light and oxygen to grow products uh that allows us to go to 25 to 100 even a thousand times faster than the traditional approaches interesting and so this is um when you say crystal you you mean that the the you're getting the um the material to not be so much layered but actually form a three-dimensional uh is it is there still layering i guess is my question so there is so there is a it's more like a playing a movie than taking snapshots okay yeah so there's individual frames uh but now they're happening rapidly so rapidly it looks like a movie okay and uh and and the objects are really gross it actually looks like if you've seen the terminator 2 uh you know a t-1000 coming out of a puddle right right we we in fact envisioned you know could things emerge out of a puddle of resin and if we could do that and could the mass of the object be derived from that liquid coming from underneath it could we grow that very fast uh and can that liquid emerge into a material that had the properties to be a final part instead of a brittle plastic which was typical of 3d prototyping great great so and so before we dive into health one more question how precise can we engineer these uh like what's the plus minus on the sizes because you made a reference to we might be able to make bespoke just made for you devices for individual patients so how precise are we and then what is the range of um materials that can be used with these technologies so you know precision it depends on what you're making you know what's needed right and so from a running shoe to a football helmet you know the printers there have a pixel size of 162 microns so that's a millionth of a of a meter it's 0.16 of a millimeter right 162 microns you know it's it's almost 20 percent of a millimeter uh and then we when you get into oral health and and things in the mouth where you can fit is more demanding we drop to 75 microns okay right which in a human hair is 100 microns right so we're talking human hair right we're talking a fraction of a human hair but we're now down to building a printer at single digit microns and you know a red blood cell is eight microns in diameter so we're going from the macroscopic down to the cellular length scales great and what about the material or the range of materials are we looking at metals or are we still thinking plastics where is all that so it's all polymers yeah uh so you know we uh we've had a breakthrough in how to do this with polymers so polymers have properties that range from high performance uh engineering materials at you know four gigapascal with stability out to well over 200 degrees celsius to things that look like engineering plastics that would be part of the dashboard of a car or the support products for a battery in an electric vehicle to dentures and replacement of things in the mouth all the way to elastomers that would be great for uh if it's energy returning like a running shoe you want to you want to bounce we have elastomers that do that we also have elastomers that dampen energy and absorb impact and then we also have water-soluble degradable uh and biodegradable kinds of products for sustainability reasons but also for biodegradation in the body so the whole gamut of polymers we don't do metals somebody needs to have an invention in metal 3d printing like we've had in polymers yeah i don't know what it is and i don't see it on the horizon yet but we're all we're just polymers no that's very impressive because you mentioned teeth which obviously have to be very hard and then you mentioned running shoes which obviously uh so this is the future of everything i'm russ altman i'm speaking with professor jose de simone about the future and present of 3d printing okay let's go to health i know that you're working on vaccines uh vaccines have been on everybody's mind what's the problem that needs to be solved and how is your team approaching it yeah so well first of all we're at an amazing uh his period in history where uh mrna-based vaccines have taken off and it's really just the tip of the iceberg mrna is gonna you're gonna see that happening in lots of different areas you know and it came from it's had a long road from silencing rna to you know all sorts of delivery approaches in oncology but it you know it's our moment it's the moment for the field in vaccines and it works right and all the nano carriers uh that were developed for oncology which really didn't pan out a whole lot uh work really well in infectious diseases now the interesting thing is that that needle well first of all the vaccines in a in a liquid formulation and we've all been hearing about refrigeration and low temperature storage never has society cared more about refrigeration than it has in the last year and if you're starting a new lab and you're trying to buy a refrigerator right now it's really hard because every other place has a bathroom backwater right now so that's a separate topic but um low temperature storage is really important for these carriers that that's a problem uh not only here in the united states but globally it's a bigger problem and then you think about dealing with malaria and measles and you know global access it's even a bigger problem that's one thing yep the other thing is the the uh the cargo the the the vaccine itself went deep into our arms it's a minor needle but it went into the muscle and we have far more immune cells and the targeted cells just under our skin in the skin than we do in the muscle and um so we've been developing micro needles that are 3d printed now micro needles have been around for about 15 years and it's a way of delivering molecules just under the skin into the dermis most of these micro needles have been fabricated using the technology from the computer industry used to make chips uh and they were making microneedles and they showed that this is a viable area of delivery but the challenge is the kind of structures you can make in a fab are limited in geometry but they're also really limited in materials right so interestingly we figured out that our our breakthrough in 3d printing which is continuous uh uses light and oxygen works really well at this microscopic level and now we're printing 3d we're 3d printing microneedles and our microneedles can have geometries that you can't access uh in a fab and we can make amount of materials that you can't access in a fab and when you say fab those are the fabrication facilities for like silicon wafers and other it type products yeah yeah and so we can make them out of what are called soft materials and instead of hardness you just described an amazing repertoire of capabilities in terms of the physical properties and what we now do is we can now use those to deliver these vaccines and so we've got a paper on a review right now at the proceedings national academy of sciences for a delivery of protein-based vaccines the old type of vaccines to the dermis and we see 50 times more antibody response delivering the same vaccine in a more precise way to the dermis than you do from a needle 50 times now would the idea be eventually to get to get more out of a single vial of a vaccine or to get a better response or both it's it's both and it's more than that too so uh not only do we you could do dose sparing you can give somebody one fifth or you can or you can vaccinate 50 times more people right with the same amount of material but i just want to bookmark that because that is a huge right now in the world that would be a huge capability and then here's another one the the immune response there's two big channels of immune response there's th1 th2 meaning the antibodies versus t cells the long lived t cells we see a much more balanced response by delivering this into that dermis layer than you do into intramuscular delivery so it's a it should be a more long-lived robust response because it's both t-cell and b cell response and we're interestingly as important the micro needles the the the the active ingredient now is in sort of like a lyophilized form of the active ingredient instead of in liquid form it's a coating of sugar actually on the microneedles themselves as a patch kind of like a band-aid yep and it's a solid state and things in a solid state are more shelf stable for long absolutely so that can take a plane ride and get dropped by uh get dropped by a parachute yeah so here's what this could be we think that micro needles could be the os of vaccine design could be the operating system that could in a plug-and-play approach could address any antigen in time of need uh it won't it could be eliminate the cold chain challenges it can eliminate the health care workers need for administration right right now there's 300 000 health care workers trying to you know administer all these vaccines right uh and we think it's scalable to billions of doses so we think it's a new approach that could really address a lot of the supply chain challenges the logistical challenges and it's a better way of a better immunological response so the the vision just to make sure i have this right the vision is that these things come in they're like patches but they have little tiny needles probably almost barely perceptible but you know so and then and you might be able to slap them on your arm or slap them someplace and that will start the delivery there may be less or no healthcare workers involved and is that the vision that's it could be if you could get it in the mailbox yeah right and ups would or amazon would deliver it or walmart would deliver to you or you'd go pick it up and yes and so it's so this would allow us you know for example the gates foundation is trying wants to eradicate measles now just like polio and you're going to need to eliminate the cold chain issues and the and the sharps and right now there's shortages of vials and all these things and so it's really get into a solid-state delivery approach for these important vaccines so i know another one of your great interests and expertise is this process of translating from discovery in the lab to actually something that can scale and really impact millions or even billions of people so where is this where are these ideas in in that in that spectrum of early idea to we're ready to ship and and what are the big uh logistical um things that you have to overcome in order to be able to deliver this i'm sure people are wondering when can i get this it sounds great yeah so we've been down this road in a um and not as important area but an important area is think about dentures right yeah that's a 14 billion dollar market uh when you get fitted for dentures it's typically uh eight chair side visits of routine you know going in over and over again to get it perfectly fit because it's handcrafted right we are now working with others that you know have digital scanners for the mouth right just like your iphone but you know and it scans through videography right and close cousin to that and it's a digital capture so we've now developed the world's first fda approved 3d printed dentures and it took us about two years to do that but you think about what's happening you now go to uh two uh two chair side visits instead of eight that's huge it's perfectly fitting instead of a person you know thinking about you know putting that blue tape in there is it rubbing here is it rubbing that's like okay that's archaic now you're giving me post-traumatic stress just thinking about my last trip to the dentist yeah so this is digitally fabricated now uh with precision that you can't replicate with handcrafted things and if you're trying to scale anything that's bespoke you've got to do it digitally with digital scale you know so we've been able to accomplish this and these kinds of materials the denture based adventure teeth are close cousins to the kind of sheet of plastic that we'd have on the patch for delivering vaccines right so we're now going through collecting all the data in animal models uh for the vaccine approach and we're working with industry all the big names in the vaccine space uh for using their vaccines and delivering them they're coming to us now because they they want to get away from the cold chain issues they want to go to dry patches they think this has gone the way of amazon right but what i think this is also lending us to is wellness monitoring which you know look um tom so and our colleagues here at stanford have been looking at ways of of monitoring the human body you know like people monitor jet engines you know and and all the sensors and you know the readouts of glucose uh you know is a really important one or oxygen is really important we only monitor two molecules like that and so the idea of can we use these same microneedles to access interstitial fluid because that's where we're delivering ah so you turn it and you pump it in the other direction out of the skin to get a sample yeah now people have been obviously looking at blood all the time for this but you know we have five times more interstitial fluid than we have blood and the molecules found in interstitial fluid mirror are the molecules that we see in blood right way better than tears or sweat does right and so the ability of having new kinds of devices for monitoring again 3d printing opens up these kinds of objects especially to get them a single digit micron resolution for new types of sensors in in that area so this is where this field's going this is the future of everything i'm ross altman and we'll have more with professor joe desimone about uh delivery and sensing of human physiology next on siriusxm welcome back to the future of everything i'm russ altman i'm speaking with professor joe desimone about 3d printing and about methods for introducing this technology into healthcare now in the last segment we talked about vaccine and vaccine delivery but i i know that in fact you mentioned mrna and mrna has also been very successful with the vaccines but it has not been so successful with in its applications for drug delivery for example chemotherapy for cancers i know that you've also been working on these 3d printing technologies for the delivery of drugs where is that what's the idea there and what's the status so one of the big challenges in oncology in particular is the systemic side effects and what's also interesting is you know imaging and early detection has taken off as a field but a lot of our treatments are still systemic when the when the cancers are locally uh identified right you only have cancer in the lung but i give you this poison that goes throughout your entire body it's crazy it's crazy so the opportunity for local regional delivery is increasingly important and you know x-rays do that x-ray treatment is very local it's focal right but chemotherapeutics and other molecules are not and so the opportunity for doing that is is high and so for example that i mentioned that the uh mrna uh delivering ontology was challenged by the nano carriers not getting it into the different barriers that you know in biological barriers for you know the stroma blocking chemo small molecules let alone big nano carriers can't get into these tissues so we're taking a much more engineering response you know people have been using polymer-based drug delivery devices bob langer pioneer the gliodel wafer and brain cancer but now we're starting to design advanced microfluidic-like devices for local delivery and sometimes are assisted by electric field assisted delivery something called iontophoresis where you can have an electric field drive molecules into poorly vascularized tumors so we're building devices uh that can drive drugs that have not been accessible through uh iv injection uh for local delivery and we're doing it in pancreatic cancer we've had a really great uh uh data that shows that we can deliver molecules like gem cytobean into these tumors and normally when people get pancreatic cancer you know those tumors are very slow growing they typically started 20 years before they were symptomatic and it's often too late or locally advanced and they often wrap around big blood vessels that make surgical resection very challenging well we've been able to address some of that with this local delivery and we've been able to show 40 regression of tumor volume for these very challenging pancreatic cancer tumors the first time people have seen tumor regression so we published a paper in science translational medicine using these local drug delivery approaches we just spun out a company called advanced chemotherapy technologies or act that is funded by vinocosa here in the area but being able to drive these drugs into these tumors and using a new advanced 3d printing devices for doing that so very convergent approach with lots of different disciplines coming together so let's i just want to make sure i understand so in the case of the pancreatic cancer is there a surgeon who's implanting this device somewhere so i just want to blow up this idea of local and and how do you get it to be local and then do you have evidence that in fact these very potent cancer medications are only acting locally and you have much lower levels in the periphery that doesn't have the cancer yeah so in this particular case yes it's surgically implanted uh directly uh above the tumor in the device uh there is a there is a tube that comes out to the belly uh picc line okay uh and uh and that could be hooked up to a wearable for local delivery of chemo or at an infusion center uh and a drug is not only it goes to that device and there's an electric field that drives the drug deep into the tumor and we can do it at a wide range of dosing yeah especially wearable yeah metronomic dosings long slow amounts of dosing right and uh and we're actually seeing 40 regression the tumor the drug concentration in the tumor is very high the amount of drug in systemic in in circulation is almost not detectable so just the opposite you know when you get an iv of these really potent chemotherapeutics the amount of drug in your your blood circulation is really high and there's actually very little in the tumor right because it's blocked and we have just the opposite so forgive my curiosity but what does this look like what can you just with using the miracle of radio can you explain what this thing that's implanted looks like all right it's a little bit bigger than uh than a quarter uh maybe about a half dollar if you remember those yes that's a little device uh that has a semi-permeable membrane and a little reservoir that's about two milli milliliters in in volume uh with a a tube and a wire that comes out to the belly uh and there's actually an electrode in that little reservoir and then you you basically uh tape another electrode outside the body opposite the device and that's enough of an electric field gradient to drive the molecules into the tumor great and so that's a great example of uh and now you can imagine wherever the cancer is liver pancreas lung that you might be able to come up with similar devices to deliver this highly um this highly concentrated chemotherapy much more local than than than so we've got a big focus on precision delivery uh using these advanced devices so you can imagine you could take someone's uh ct image or mi other tumor and actually make it bespoke there too right for a local delivery so those are the fields we're going after so so this is this is very exciting and i did want to turn in the last couple of minutes i it's a little bit of a turn but i think it's very important you've also been in uh involved in a lot of issues of diversity and trust in in bioengineering and in medicine and healthcare and while that's a great topic you might not think that a person who's a 3d printing whiz would be doing this so can you make that connection for me and tell me the kinds of things that this how this impacts your work well everything we just talked about uh was i think it was self-evident about the disciplinary diversity right in chemistry material science software hardware all coming together and everyone gets that but you know human diversity also brings a level of innovation that's really important diversity at its core is a fundamental tenet of innovation whether it's disciplinary diversity or human diversity and you know what's i've i've had researchers and trainees from all over the world uh and you know when somebody grew up with not much money they think about problem solving very differently than somebody grew up with a lot of money and that was evident to me early in my career and that that's that socioeconomic diversity gender diversity uh expect experiential diversity is is part of the canvas of our innovation uh for the for our group and so i think one leave so i think our the hallmark feature of our group is we're trying to do new things try and do innovation and that requires diversity in a broadest broader sense to drive that and so it's getting that right and then what's also clear is you've got to be clear about your values when you're clear about those values and you're you talk about that then you can become a destination for excellence wherever it is people know they can go there and feel included and can be long and so um you know so that's a big part of our group a long time ago were part of a meeting that was going to be in south carolina back in 2000 when uh the the confederate flag was hanging over the state capitol and there was a boycott from the uh naacp and we honored that boycott and didn't go to the meeting and then the chemistry community started talking about us you know leading like that and that story got out and we became a destination for excellence because of those things and so i think it's important to be clear about one's values and a role that diversity both human diversity and disciplinary diversity drive the innovation engine it's fantastic to hear and you know that theme has come across in in this series of conversations that i've been having with uh innovators it comes up time and time again that they see the impact of their diverse teams and it's not theoretical it leads to faster progress on all the problems that they're trying to solve it's mathematical you can just see all the different inputs coming together it's like combinatorial approaches and the white and trying to cast the widest net uh in diversity both disciplinary and human is really important thank you for listening to the future of everything i'm russ allman if you missed any of this episode listen anytime on demand with the sirius xm app
2021-06-28