TEDxBigApple - Robert Langer - Biomaterials for the 21st Century

thanks so much thank you what I'd like to do is talk about materials biomedical materials in particular and I'm an engineer chemical engineer as was mentioned but one of the what I did when I graduated from college is I actually went to work in a hospital and I would and one of the things I started doing was working in medical materials and I was very surprised actually when I started looking into this how did materials get into medicine I would have thought maybe by chemists or material scientists but when I looked at this I saw pretty much - the entire 20th century they were always driven by medical doctors and what the doctors did is because they urgently wanted to solve a problem they'd go to their house and they'd find some object in their house that would resemble the tissue or organ they'd want to fix then they'd use it in a person so for example just to give you a few examples take the artificial heart so here what happened was is that the scientists at the NIH clinicians at the NIH wanted to make an artificial heart and they said well what object kind of has a good flex life like a heart and they said a ladies girdle that by the way was 1967 but that's what they did they made the artificial heart out of the ladies girdle and now 45 years later that's still what they make the artificial heart out of because once you start down that path from a regulatory like FDA standpoint it's very hard to change but the artificial heart hasn't worked very well right blood it's the surface of the artificial heart and it can form a clot that clot can go to the patient's brain and cause a stroke and they die but if you think about it something's designed to be a ladies girdle that's probably not the optimal blood contacting material and this problem pervades all of Medicine I have a few other examples here just to highlight one other one breast implants one of those was actually a mattress stuffing you can probably think of the logic and so one of the things that I started thinking about as an engineer when I saw this is I thought maybe we can do better rather than take these materials from our house maybe we can ask questions what do we really want in these materials from an engineering standpoint biology standpoint chemistry standpoint and then could we synthesize them make them by chemistry now I'm going to give you some examples some that have already been done some that might be three to five years out and some that will take you know even longer but I wanted to give you feel first I'm going to give you an example of something we've already done but I also want to highlight in this something that I think is really important for everybody here that talks about innovation which is not only what you do but also sometimes the opposition you get when you do it so when we started this work and this was actually in the early 80s the only material polymer that was fda-approved was the polymers that degraded and showed what we call bulk erosion that means they dissolve like this so if you put a drug in it you could imagine if it dissolves like this that if it was a toxic drug like insulin or an anti-cancer drug when this happens it could just stump out and that could actually kill someone so we said that's probably not so good so we said from an engineering standpoint how should we want that polymer to dissolve and we said well what we really want is a polymer to dissolve like this what we call surface erosion and we went through a very detailed chemical engineering design analysis to make a family of polymers which we called polyanhydrides that did exactly this and by changing the chemistry we could make them last for almost any length of time and then one of my friends a Henry Bram who is a neurosurgeon was just starting at Johns Hopkins said well could we come up with a way maybe to use this for treating brain cancer patients this was in 1985 and in particular he would be treating these patients and and of course it's a terrible disease people are almost always dead within a year and the what he wanted was asking these could we do something like this could he operate in the patient he's going to they're going to operate anyhow but before they close the patient's brain up could they take a chemotherapy drug which you normally give systemically throughout the body could you give it locally right to the target and the way they do that is could they put little wafers in the brain right before they close it up now this drug normally lasts 12 minutes but we could make these polymers yes for months or years so that's what we did we locally delivered the drug from a polymer wafer that in this case lasted for a month and the power of this is that you get local chemotherapy high concentrations in the brain where you want it to be and low concentrations and the rest of the body where it causes harm now if the point that I mentioned and I want to highlight this is that when we first in eighty put forth these ideas about new materials and that they could be used in medicine what happens in if you're a professor and you want to do these projects you have to raise money the way we raise money is we write grants and then mostly in my case those grants would go to the National Institutes of Health and they would be reviewed by what's called a study section which are professors and other universities that tell you what they think about it and decide whether you should get the money or not and we did terrible got all types of opposition I'll just highlight some of these in 1981 we first proposed it the chemist said you'll never be able to synthesize the polymers but I had a very good graduate student named Howie Rosen he later became president of the Al's a corporation twelve billion dollar company and he synthesized them and then we sent the grants back and the scientists said well but you know these polymers are very reactive whatever drug you put in they'll react with it won't work I had another couple of postdocs a bob Linhart he's now a very famous professor at RPI and kamilly young also very famous professor at Duke and they worked out ways so that that didn't happen and then people said still won't work these polymers are fragile to break in the body another couple of postdocs Edith Mathias who now is a very well-known professor at Brown University and avi dome who became head of a major department at Hebrew University in Israel and they showed that they chose that wouldn't happen then people said that the materials would be toxic but here I had help from Mike Barletta who's now president of Scripps in California and and Cato Laurencin who did a lot of the toxicology studies later became a president of University of Connecticut's School of Medicine so anyhow this kept going on and on until 1996 when the FDA approved it it was the and it was the first time and actually over 20 years they ever approved a you know a new treatment for brain cancer and the first time they ever approved this idea of local chemo therapy so you get this kind of opposition one of the things that I wanted to say is you can probably tell from the way I'm speaking I'm really proud of how well all our graduate students and postdocs have done they've become head of major departments major corporations throughout the world whereas the reviewers at the other universities they haven't done so well now now now now I'd like to show you what this operation looks like but if anybody's squeamish and doesn't like the sight of blood don't look but here here is a little way for going into the brain you know by the way it's very hard to get good advice when you give a talk but about 14 years ago I was giving a lecture on this at MIT to a group of engineers and my wife came to the lecture and I said at the end of it what did you think Laura and she said well she said Bob the talk was all right that by the way is extremely high praise but she said you know you have that bloody slide on for over ten minutes you know and all those poor engineers were turning green so now I give a warning and show it quickly anyhow this was this was a little bit of some of the clinical data showing that and again this is this is probably going to be limited to patients that have localized tumors but you can see even after two years you get a five-fold increase in survival also the principle of local chemotherapy for polymers that we advanced not only got to be used here and in other types of cancer but really where it's made an even greater impact is using the very same idea later on in drug eluding stents this in fact was done by another of my students Eleazar Edelman is now a professor at Harvard and MIT as well as different companies and now you can take these stents like if somebody has heart disease they're used in over a million patients a year you put them in but sometimes you get the the vessels get clogged because of the injury and now they can release again and I cancer drugs like taxol and that prevents it from happening also I started thinking of other ways materials might be helpful and and and just to give you another idea and it really goes along with what Brian Roberts was saying earlier you know one of the things that's happened in medicine so that you don't have to stay in hospitals as long is a whole idea of minimally invasive surgery thirty years ago if you had a gallbladder operation they'd make a big incision in you and they'd take the gallbladder out but because they made that big incision you'd be in the hospital for days and you wouldn't be back to work for months now they do something called minimally invasive therapy they make a tiny incision they put these scopes down the hole and you can take the gallbladder out just through those that little hole you're out of the hospital in less than a day back to work in a few days so I started thinking you know if you could do that if you could take objects out through those holes maybe we could put all kinds of medical devices in through those holes even bulky medical objects now that might sound like science fiction but the idea I had is maybe we could make materials that under one set of conditions could have one shape like a string to go into that hole but under another set of conditions say when it's warmer like body temperature it could change into whatever shape we want so andreas lend line one of my postdocs synthesize the number of these we actually worked out ways to change it by temperature going from room temperature to body temperature or even heat I'm sorry even light like a fiber-optic one wavelength to another so I'm just going to show you a couple videos first video I'm going to show you a string at room temperature then it's going to go to a body temperature water and I hope it changes into a coil like this so here's the video here's the string at room temperature air goes into body temperature water and it does that let me give you a second example let's say you at a surgical wound outside the body like in your face or your arm well if you if you had a wound like that you'd want to tie a suture it's actually not that hard to do I could even do it though you probably wouldn't want me to but um what about inside the body what if you had a wound in the stomach or the lung how could you tie the knots then so we thought what if we could make the knots tie themselves what if we could loop in a loose knot like a lasso at room temperature and then have it just tighten at body temperature so let me just show you another video here's the loose knot at room temperature air and now it goes to body temperature water and it tightens let me give you a third example and this is again might seem more space-age but we hear you know you always hear about computers and chips and of course they're they're used in all kinds of things and computers and television so one day I was watching a TV show on that and I thought well maybe we could use it in a drug delivery system and so with Michael CIMA one of my colleagues and John Santini our student we made a very different kind of this is a more of a chemistry chip where you could put little Wells in cover them in this case with gold and you could actually put multiple drugs different doses of the same drug in or many drugs and literally you could think theoretically years from now of a pharmacy on a chip and we use kinds of new photolithography and other techniques to make these chips this is an early one thirty four wells in the top thirty four in the bottom in the United States time just for comparison and by the way they can be mazed any size or shape and they can even be made injectable let me show you how they work here's a well it's covered with gold but we're going to apply and you can do this by remote control by telemetry the same way open up garage door we can apply a small amount of voltage and in less than ten seconds the gold comes off when it does the drug can come out so no drug could come out for two years then you trigger it and it all could come out and just as a proof of principle here we've delivered different amounts of drug at different times and here we've delivered multiple drugs at different times one of the things that's very exciting is in about two weeks we coming out with a paper in a journal called Science Translational Medicine which is the first human trial of this and what we did here is we took parathyroid hormone and and basically that's a drug you want to give Ana pulsatile fashion if it's given continuously it causes bone resorption but it's very important to give that for women with osteoporosis and a tiny incision was made in a doctor's office the women didn't hardly even know that it's there and then what's amazing is now what's been done in this clinical trial is just simply over special immediate medical frequency wavelength you just give the signal out comes the drug whenever you want it to so you and it actually shows less variation to the patient than injections so and this was done over a six-month period last example that I wanted to give you is could you actually someday not combine cells to make new tissues not initially organs the organs as Brian talked about you know that's many years away tissues may not be quite so far away and I'll give you an example or two of that so the idea that Jane piccante and I had was could we take cells and those could be stem cells but we've made the slide up before people used stem cells this was in science a number of years ago but you could take virtually any cell type put it on the right kind of scaffold grow it outside the body and then you could make virtually any any tissue you want that was sort of the idea now some tissues are much easier than others and the tissue that's been most advanced and based on some licenses from us and other things is human skin and let me just give you an example of that which is now actually on the market and and and here you see a little boy who's very badly burned and what you can do though is take the product which in this case is new and a ttle skin fibroblasts and you can on the polymer scaffold you can put it in the child at the time of injury it looks like this but if you come back three weeks later looks like this if you come back six months later he's pretty much healed these are now approved both for patients with burns and patients with diabetic skin ulcers and and so that's one example another example and this sort of relates to the ear can you make cartilage could you make cartilage now we're actually doing a couple things the ear thing interestingly enough even though that got a lot of publicity number years ago we're actually working Jay Vacanti who's the my collaborator and I with the United States Army because patients come back from Iraq and Afghanistan unfortunately without body parts like years and other things and so we hope actually in the next couple years that we'll actually be able to help people like that but even short of that there are patients with congenital defects so here's a little boy who doesn't have a chest covering his heart he was 12 years old at the time but like other 12 year olds he likes to play baseball but you could imagine if he ever got hit in the chest with a baseball he could die so actually Jay operated on him we made a polymer scaffold gave him his own cells and actually recreated a new chest the last example I wanted to give you still obviously in the laboratories could you even help people with spinal cord repair so I'm just going to show you rats but but here what we did is we made a special scaffold with in this case neuronal stem cells we did this with Evan Schneider and Ted Tang and Aaron Levesque who is one of my graduate students now professor at Case Western led the study so we actually did about 50 of these animals and what I'll show you in the first one which is the mean of the control group is what normally happens so what you see when you look at this at these animals is two things at least these trouble supporting his weight and the paws are splayed in a rather awkward fashion and there's actually a scoring system you can use for these animals so here it's about a five 20s witness would be optimal it's a BBB scoring system now then what we did this is actually a hundred days after the injury and then what we did is we actually did the same kind of thing but we took scat see specially-designed scaffolds along with neuronal stem cells and we put these in and we also filed the animals and know that all these were followed for 400 days since that's a hundred days let me just show you an experiment again the mean of the experimental group also at a hundred days and here you see this can this is hardly a cure still a lot to do but he can bear his own weight and also the paws as you see are splayed in a much more normal fashion again out of a maximum of twenty he would get a fourteen and twenty is what a regular rat would get five was what the rats in the mean of the last group got notice the paws splayed much more normally my wife told me not to leave that on too long either what's happened now is there's even a company in vivo therapeutics they licensed this and now they've done this in primates they've gotten pretty similar results in the hope is again to try it some man or another to move this to the clinic in the next couple of years but in a broad way what I've wanted to try to get across this evening is really I think that material science and medicine and actually material science broadly we've heard all kinds of great talks about biomimicry about new materials in in construction and all kinds of things I think material science is an incredibly exciting area that for which there's an enormous amount of innovation that I think can really transform our society in a very positive way thank you very much

Channel: TEDx Talks

Views: 93,849

Keywords: ted talk, tedx talk, ted x, Robert Langer, tedx, ted talks, tedx talks, TEDxBigApple, ted, TEDx

Id: uta5Vo86XL4

Length: 17min 50sec (1070 seconds)

Published: Fri Mar 02 2012