professor mark saltzman:so, today i'm going to continue to talk aboutapplications of biomedical engineering,so as sort of a way to bring together some of the conceptsthat we've talked about over the last several months.tuesday, i focused on applications in cancer.we thought about how imaging techniques, how instruments thatdeliver radiation, how molecules and cells couldbe used to treat cancer. today we're going to--the focusis going to be on artificial
materials.biomaterials, which are widely used inmedicine now and were produced largely through the work ofmaterial scientists and chemical engineers,and biomedical engineers over the last 100 years or so.we'll talk about some of the difficulties with creating amaterial that can be implanted in the body,and we'll talk about some of the applications of thosematerials, particularly in artificial organs,is where i want to end up for
the day.these are two pictures from the text that i present,just to show you that the idea of using artificial materials toreplace tissues that are lost for one reason or another,is not new. the one picture here shows aremarkable discovery from a mummy that is something like3,000 years old. this particular mummy was awoman who had a toe that was amputated for some reason.the toe was replaced by a synthetic--well not a synthetic,a natural material,
fashioned to look like a toe.this is made of wood. just to acknowledge that peoplehave probably tried to use the materials that were in the worldaround them to replace parts of the body that were lost totrauma or disease for thousands of years.we've gotten quite good at it in some senses,but there are still significant problems left to solve.the other slide, here, i wanted to show you whati think is a remarkable material.this clear part here is a lens
that's actually implanted intothe eye. it's like a contact lens butit's permanently placed inside the eye over your natural lens.this is for people that have very severe difficulty invision, because the properties of their natural lens havechanged. so, you can put an artificialmaterial, so it's made of a polymer, inside the eye.it can stay there for the rest of their lives restoring theirvision to near normal and requiring no other effort ontheir part.
they don't have to put in thecontact lens everyday, because it's there inside theireye all the time. what kinds of materials arethese that we can use now to replace or restore the functionof tissues that are damaged? well, many of the materialsthat are used, most commonly,and with the most success now are polymers or plastics.we've talked about some different aspects of polymersand medicine throughout the course here.what i wanted to show you on
this slide is--and again notthat you would memorize or even be able to read all the detailshere, but there are a large number ofdifferent synthetic materials that now are produced andregularly used in medical applications.polymers, as you know,are manufactured products. most of them are made fromproducts that are derived from petroleum or oil.they're organic molecules, typically small units that arepolymerized together to form
long chains.because the individual molecules in a polymer are longchains, when you put a bunch of them together in a material,they entangle together and they give you a nice materialproperty. you're not falling down to theground now because the plastic chairs that you're sitting onare quite strong. this polymer material thatmakes up the base of the chair is able to support your weight,and does it very reliably for a long period of time.you also notice that these
chairs, if they were made out ofwood they would be very heavy. these are quite light,you can pick them up easily. if they were made out of metalthey would be much heavier, they might be stronger but theywould be much heavier. one of the advantages ofpolymer materials is that you can make things that have quitea lot of strength but are still fairly light.that's one of the advantages of polymer materials.you can also change properties of the polymers.that's one of the things that
engineers have learned how to dowith quite a large degree of sophistication over the last 100years or so. you can make many differentkinds of polymers, now, that differ in thechemistry of the monomers that are linked together to makethese long chains. you can, of course,change the length of the chain. you can make materials that aremade up of polymers that have very long chains or shorterchains. as you could imagine,that changes properties,
like the material property ofelasticity that we talked about a few weeks ago.we've discovered, mainly through a process oftrial and error, that many of these materialsare biocompatible. that is, you can put them incontact with tissues of the body, and the side effects ofimplanting that material are not severe.now, in a few slides i'm going to tell you more about how thebody responds to biomaterials. what you'll see is that theresponse can be very mild to
some materials that inert,and can be quite vigorous to materials that aren't so inert.one needs to select a material that's appropriate for theapplication that you want to use it for,has the right properties for the application,and also has the right extent of compatibility in the tissueyou want to use it in. this is just to show you kindof the range of materials that can be used now in some of theapplications in which they're used.we'll talk about that as we go
through the lecture today.one of the applications i've already talked about lastweek was making tubes of polymers,tubes of polymers that can be used to replace the conduitsthrough which blood flow. this slide shows you someexamples of arterial grafts, so synthetic materials that areused to replace a segment, let's say of the aorta.this might be needed because the patient has had some kind oftrauma where their aorta has become ruptured like in a caraccident, for example.
it's deep within your body soit would have to be a pretty significant trauma in order tohurt your aorta. more commonly,sometimes there are diseases of the aorta where the wall of theaorta becomes weak and causes what's called an aneurism,or a weak spot in the artery that can balloon out.obviously, if that becomes so weak that it bursts that's amedical emergency. if you diagnose those earlyenough then you can replace that segment of the aorta with asynthetic polymer.
this has been done for decadesnow, there are several different materials that can be used inthis way. because the aorta is a largecaliber vessel it stays patent, that is the blood can flowthrough continuously for many decades.this is true for vessels that are larger than say 5 mm indiameter. as the size goes down,it becomes more difficult to use synthetic materials in theseapplications. you can't use a syntheticmaterial like this in the
coronary arteries,for example, of the heart.we talked about that several weeks ago.i'll show you some pictures that show you why that wouldn'twork in smaller diameter vessels in a few moments.most of the materials that are used here were initiallydeveloped for other purposes. the two most common materialsthat are used in conduits like this are dacron,which is a synthetic polymer that was first--was used forlots of things but it's made
into clothing,for example. surgeons like it because it hasnice properties, you can sew it easily.imagine that a material that's going to be used in anapplication like this, a surgeon has to be able to sewinto it fairly readily. it has to be able to hold asuture, and that suture line has to make a neat connection oranastomosis with the native vessel.surgeons being able to sew into the material reliably is,obviously, an important part of
the design.dacron, a textile, has a nice property that way.the other material that's used often is a material you'refamiliar with called gore-tex. gore-tex is basically teflon,its teflon that is treated in a special so that it becomesporous. one of the properties ofteflon, you use it as cookware, for example,because things don't stick to it.it's not a sticky polymer, it's fairly inert toparticularly proteins that might
stick on the surface.on it's own, it would not be porous and soit wouldn't allow any molecules to pass through.gore-tex, on the other hand, is fashioned--and this is apicture of gore-tex at very high magnification here,so it has small pores in it. pores that are so small that adroplet of water can't pass through, but molecules of watercan. that's why gore-tex is souseful as a material for hiking for rain gear,it allows water to evaporate
through it but doesn't allowdrops of water to go in. you can make a waterproofmaterial that still allows your body to sweat and for vapors tocome off your body but doesn't allow water to go in.that same property makes it useful for arterial grafts aswell. there's some facts on thisslide that show you how many of these operations that use thesekinds of materials are performed every year.another example of using synthetic materials like that isin the heart valve.
we talked about how heartvalves function several weeks ago.we talked about how your heart becomes very inefficient in itspumping action if the valves don't work properly.there are diseases of valves that are not uncommon.many people, decades ago,died because--at relatively young ages because their heartvalves would stop working. their heart,even though it was beating properly, could not deliver theflow rate that was needed to
sustain life.here's an early example of a mechanical valve,a totally synthetic material that could be used to replace aheart valve. now, this is a collar here,which is made of a textile that can be sewn into the spot,to the ring of tissue where the heart valve goes.you can see that white material there, there's a metal ringunderneath it and on both sides of this ring there's a cage,a small cage on the bottom and a larger cage on the top.the heart would be down here,
the ventricle would be downbelow this here. if there was pressure on thisside, it would force the ball up.when the pressure in the left ventricle got to be higher thanthe aorta, it would force the ball up.then, flow would go out because the ball sitting in thisposition completely seals the opening.when the pressure pushes the ball up then it opens up apathway around it, so blood can come out throughthe sides and the ball goes up
but it doesn't go away becauseit's constrained by this cage on the top.now, when the pressure here gets higher than the pressuredown here, the ball falls back down and it reseals.so, it does exactly what we wanted or what we described theheart valve is doing, that is opening up when thepressure difference was right, when the pressure was higher inthe ventricle then the aorta, and then closing again when thepressure in the aorta was higher than the ventricle.now, the problem with this
is you remember how the normalvalve opens, it opens like a doorway.the normal valve opens like a doorway, so the part that's shuttotally opens. there's a very clear path forflow. in this kind of a ball valve,the ball is still in the way. the fluid has to go around theball in order to eject into the aorta, for example,if this was an aortic valve. because it has to go around it,there's an obstacle to blood flow creates an additionalresistance.
your heart has to work harderin order to overcome the resistance of the flow goingaround this large ball that's in the center.it works well as a valve but it's not a very efficientvalve, in that it requires your heart to work more to get acertain flow rate because it's blocking--this ball is blockingthe center of the flow. in addition,you can imagine this ball slamming up and then slammingback down. up and down,could cause mechanical damage
to the blood and it does.blood consists not just of water and molecules but cells,like red blood cells, and these cells are sensitiveto mechanical forces. everytime this valve opens andcloses it breaks a certain number of blood cells.that's also something that you can live with but isn't perfect.the most--a better design was made in, i think about the1970s, it's this valve that's shown here.in many ways it's similar, it has the same kind of atextile ring and metal on the
outside.now it's shown sort of end-on, so you're looking through thevalve and what you don't see here are two,what are called leaflets. these are made of metal andthey fold like this, close like this and then theyopen like that. it's more like a swinging doorand also responds to pressure because it can only open oneway. it goes like this;it won't go like that, so it only opens in onedirection in response to a
pressure drop and then it closesin the other way. this is now the most commonlyused design for a totally synthetic valve.still, a popular valve that's used are these two valvesthat are shown here. this is one is from a cow,this one is from a pig, and they're natural valves thatare recovered from the animals. then, they're treated,they're cross-linked with a chemical so that they becomepermanent structures, non-living structures now.these sort of bio-synthetic
valves, what's called in thecaption here, a bio-prosthesis.prosthesis just means replacement, so this is derivedfrom natural tissue is an alternative to this mechanicalvalve. physicians will use one ofthese types of valves or another depending on which of yourvalves needs replacement, what their own experience iswith people that have diseases like the ones they're treating.there are at least several options available.one of the problems when
you put any synthetic material,or any material other than your own tissues,in contact with blood is that you will start a process calledcoagulation or blood clotting. of course, this naturalreaction is important to our lives.if you damage a blood vessel, the blood vessel becomesruptured. all of a sudden,the blood is exposed to a surface it's not used to seeing.you damage a blood vessel and instead of the blood flowingthrough a nice tube that has a
very consistent endothelial celllining, it's now exposed to the tissueoutside when the blood vessel gets ruptured.when it's exposed to the tissue outside, a series of chemicalreactions gets initiated. that series of chemicalreactions is called the coagulation cascade.it involves proteins that are also enzymes that go from aninactive state to an active state.this is described in the book in some detail.i'm not going to ask you
questions about the moleculardetails of this. i want you to just sort ofunderstand the concept, that a protein in the bloodgets activated by exposure to a foreign surface.it creates an activated enzyme, which then activates anotherenzyme, which activates another enzyme on through this network.the final result is that a molecule in your blood,called fibrinogen, it's converted in to across-linked network called fibrin.exposure to a foreign surface
sets off a series of chemicalreactions. the end result is that anatural protein in your blood that's normally dissolved andjust flowing around in your blood called fibrinogen getscross-linked into a gel or semi-solid material.this is the formation of a clot. now, when this reactionhappens, this cross-linking of fibrinogen into fibrin happens,they're usually cells that are trapped there as well becausethese cross-linking reactions occur in blood and there's lotsof blood that gets cross-linked
into this network.you form a semi-solid structural material that sealsoff the area of the blood vessel that's damaged.blood now stays within your circulatory system,the bleeding stops. that seal that gets made is achemically cross-linked version of fibronectin,and you know it as a blood clot.you cut yourself, you see a clot later,it looks red because--it looks red but it's solid.it looks red because there's
blood cells trapped in it,red blood cells trapped in it. it's solid because the basis ofit is this cross-linked network of proteins.this happens if you expose blood;anytime you expose blood to a foreign material.it happens if you put a heart valve, an artificial heart valvein the blood pathway, this clotting reaction willstart to happen. that's what's shown in thisslide here. you can't see it too well butthis surface would ordinarily
look smooth.it doesn't look smooth because there are proteins coagulated onthe surface here. these proteins of fibronectinthat are being converted into a fibrin gel.there are also specialized cells that also find thesefibrin networks, and they spread out to helpform a barrier. these cells are calledplatelets, and you know platelets are also important inblood clotting reactions. one of the problems withevery synthetic material that's
used to replace a component ofyour circulatory system, like a heart valve,is that you form a thin layer of clot on the surface.now, what you hope is that that happens within the first fewhours of when the heart valve is replaced.then doesn't happen anymore because it becomes a sort ofnatural biological surface now, and your body tolerates it.it requires--this only happens with certain kinds of materials.that's one of the criteria for selecting materials that areused as heart valves,
is that they have to be able tosupport sort of a mild clotting reaction;a mild, not a severe, clotting reaction.what happens if this clot keeps forming on the surface?the clot gets thicker and thicker on the surface andeventually, since there's blood flowing by,pieces of that clot could be expelled from--or detached fromthe surface of the material. they would flow into your blood.if they flowed up into your brain, for example,they could clog smaller
arteries inside your brain andcut off blood flow to that region.that process is called embolism. embolism is when a smallparticle is released into your bloodstream, and embolism cancause all sorts of unwanted effects.so, a bad heart valve might give you a stroke in the brain.this is one kind of reaction to a biomaterial.these other two pictures show you other kinds of reactions.here's a material labeled as m here that's implanted under theskin.
what you see is that after timethis unusual layer of tissue forms, this is called a part ofthe foreign body reaction. your body tries to form a kindof scar around the material. i'll show you how that happensin a cartoon in just a minute. materials that are very--thatare not so inert can cause extensive cellular reactionslike the one i show on the bottom here.these dots here are cells from your inflammatory system.they're neutrophils and macrophages that are collectingat the site of the foreign
material.the material here was a mesh and you can see where the fibersof the mesh are, where there's clear dots here.you can see there lots of cells that are recruited.if you showed this to an experienced pathologist he wouldsay these cells are coming in as part of the inflammatoryresponse, as part of the unwantedresponse to this material. every material produces adifferent reaction when you put it into the body.the details of the reaction
depend on the chemistry of thematerial, its mechanical properties,how its surface is treated, if the surface is rough orsmooth. from an engineeringperspective, those are all things that we can potentiallychange. we can design materialshopefully that minimize the response of the body to it.in general, you can't make the response go away,and the response appears to have some generalcharacteristics.
there's general ways that yourbody responds to all materials and those general ways are shownin this cartoon. in the first few minutes,seconds, or up to an hour, when you put a material intothe body it becomes coated with proteins.now, where do these proteins come from?if this was a material that we used in the--in contact withblood, those proteins probably came from the blood.if this was a heart valve, for example,then these proteins probably
came from the blood.if you looked at the proteins, they'd be primarily theabundant proteins that are naturally abundant in blood likealbumin and fibrinogen, other kinds of proteins likethat. protein absorption happens veryquickly. within the next few dayscells will start to accumulate around the material.it appears that--what we know now suggests that these cellsare recruited to the material because of the proteins that areabsorbed.
you can understand that--youknow that proteins are--surround all the cells in our body.we talked about extracellular matrix and how there areconcentrated gels or proteins that surround almost every cell.cells like to stick to protein layers.if you have a material that's coated with a protein cells willstick to it. now, the first cells thatarrive and that stick are cells of the inflammatory response.in the inflammatory responses, the natural process of yourbody responding to some
potentially harmful event,these cells are moving around in your body all the time.they flow through your bloodstream;they crawl through your tissues, they're looking forsomething potentially bad to happen.then when it does, they try to start the healingprocess. these cells recognize thatproteins are attached to the material and they begin toaccumulate at this site here. the first cells that arrive areneutrophils, the second set are
macrophages.now, those are the cells that i show accumulating at highconcentration around this material here.what they do is they start the healing process and they do thatin a variety of ways. one is that they releaseenzymes that try to digest whatever is around.they also send out signals to recruit other kinds of cells tocome in. that's what's shown in thissecond stage here, is that the cells condense intoa layer.
they form what are called giantcells, which are basically macrophages that fuse togetherto form a giant cell, which in some circumstances cancompletely encapsulate this material.they send out signals to the rest of your body that say,'something's going on here, we need your help in healingwhatever is happening at this local site.' if this was a splinter, for example,that you got underneath your skin your body's response to itwould be to form a scar all the
way around it and to try todigest it. if you've ever had a splinterthat you couldn't get out you might have waited for a fewdays, or a few weeks. eventually, the splinter getscovered with some kind of a tissue and it comes up towardsthe top of your skin and eventually gets ejected fromyour body. that's one kind of a healingresponse that's natural. if that splinter was too deepit would just get totally covered with a scar,scar all around it.
the cells that are in the scartissue would be secreting enzymes and digestive chemicalsinside trying to dissolve the splinter.if it was made of wood, eventually it would dissolveand it would completely disappear.if it's made of a synthetic polymer that doesn't respond--ordoesn't get digested by those chemicals what happens is that astable scar forms around this material that never disappears,but the material is isolated now from the rest of your body.now, i mentioned that different
materials produce differentlevels of response like this. some of the responses are verymild in that you get very little protein absorbed,you get very few cells recruited to the site.you'd get, not a scar, but maybe a thin layer ofcellular tissue that would form around the outside.some responses are mild and those are consideredbiocompatible, and some are more vigorous andthose are considered to be not so compatible.it happens with almost every
material we know.let's talk for a few minutes about a completelydifferent kind of application. again, this one that imentioned a few weeks ago when we were talking aboutbiomechanics, and that is replacement of thehip. i just showed you this drawinghere to remind of hip anatomy. the pelvic bone is here,which form a girdle at the level of your waist.there's a cup inside the pelvic girdle called the acetabulum.into that cup the head of femur
fits in a ball-and-socket joint,so that your hip has all the range of movement that we talkedabout in class and in section a few weeks ago.if there's a disease of this bone and this needs to bereplaced, then the general procedure now is to replace notonly the part--this part of the hip that contains the joint,the ball, but also to replace the socket as well.so, you create a total hip replacement where you've got amaterial that you put into the socket,and a material that you put
onto the femur to fit into thatsocket. i showed you this picturebefore and this was a--this is a design of a material like this,you see a metal cup that serves as the new acetabulum.you see a metal ball that is attached to the femur,and this ball fits into this socket.now, if you just had metal on metal and you tried to move thatmetal ball inside that socket, that doesn't work so well.metal on metal, there's some friction betweenthese two.
if this was a motor and you hadmetal on metal, you'd put oil in between thereto lubricate. this is not possible in thissituation. you put something else in thereto lubricate and the something else is this white material.it's a layer of polymer, a thin layer of polymer thatalso forms a cup, fits exactly into thisacetabulum piece. the ball of the femur,then, is gliding on this smooth polymer piece.these polymer pieces have been
made of a variety of differentmaterials over the years, teflon, and now most of thepieces now are made of high density polyethylene.bobby?student: [inaudible]professor marksaltzman: modern hip replacements,and i'll show you some new designs, now typically have alifetime of closer to 20 years. i'll tell you why many of themhave to be replaced after about 10 years, the older designedones. design has gotten better overtime with these,
and i'll talk about some of theways that it's gotten better. one of the problems is thatthis piece here, this ball of the femur,this part that's going to replace the hip has to be veryfirmly attached to the rest of your--to the rest of the bonesof your leg, to your femur.if you're standing on one leg, all the weight of your body isreally being carried by this piece of material here.that's why they're made out of metal because metals are strongand relatively light,
and you need a strong material.plastic wouldn't work in this setting.plastic wouldn't work in this setting because plastic is tooelastic. most plastics are too elastic,whereas metal is stiffer and can hold your weight.what you didn't see in that previous picture is that there'sa long piece here that goes down into the bone and this longpiece that goes into the bone allows you to fix the ball ofthe femur to the rest of the femur.it's fixed because this metal
part down here goes down intothe shaft of your femur, and then is held there.it's kind of like a long, thick nail that goes down intothe length of the bone and what you hope is that that largesurface area in contact, metal to bone,holds the whole piece into place so that the hip operatessmoothly. now, one of the goals ofthis would be to create a design that naturally integrates intoyour bone and, what's called on this,a 'self-locking mechanism'.
what would a self-lockingmechanism be like? well, maybe you'd put holes inthis material like the holes shown here so that your bonecould grow through it. as your bone heals around thisimplant what if bone could grow though the material,then you'd have bone on both sides sort of locking it in.that would be the perfect design, that would be a--notperfect, but that would be a good design.the problem is that's going to take some time.you want the person to be
able to stand up and walk,and move around, and function in the periodbefore that happens. what is usually done is thatanother material is used to lock these materials temporarily inplace. that material is called bonecement; it's a polymer that can bepolymerized when you shine light on it.it's not too dissimilar from the materials that's dentistsuse now to fill cavities. if you had a cavity filledrecently they put some sort of a
material into the cavity andthen they shine a light on it. they put on the goggles andthey cover up your face and they shine a light on it.the polymer that they put into the cavity polymerizes and formsa hard surface. here, they put the polymer allaround the acetabular cup, they put the polymer into therecess that they push the bone into.then, they shine light on it so that it starts to--so that itpolymerizes and hardens and forms a very tough material thatfixes this thing in place.
that's called bone cement andthe material is polymethylmethacrylate.you can see that this now involves at least threedifferent kinds of materials. there's the metal that's usedto make the implant, there's the polymer liningthat's used to lubricate the joint between the two metals,and there's the other kind of polymer, the cement that's usedto fix this in place in the--in contact with your natural bone.here's an implant that was removed from a patient after,as bobby mentioned,
after maybe 10 years they foundout that their hip wasn't working so well anymore.they were starting to get pain from their hip joint or theyweren't able to move it through the whole range of motion thatthey had been able to move it through in years past.in this particular case, this joint was removed.here's the ball, here's the acetabular cup,there's no polymer anymore. where did the polymer go?one of the problems with older designs of these materials,particularly when they use
teflon and not polyethylene,is that over time as you used your hip while,there wasn't much friction between the metal ball and thepoly--or the teflon cup, there was enough friction wherethe teflon would start to wear. it would start to wear down andit would get thinner and thinner over time.eventually, as in this case with this particular patient,could totally disappear. if it disappeared then you'vegot metal on metal now, harder to move your hip,probably causing pain when you
move it as well because thepieces aren't lubricated as well.in addition, what happens is that when thismetal is moving against the polymer, it wears down but thepolymer doesn't vanish, it has to go somewhere.what most people think is happening is that tiny particlesof the teflon or the polyethylene are being createdlocally. as wear happens,you're wearing down the material, you're creating manysmall particles of the material
that are released.those particles, then, can start an inflammatoryresponse. your body will start to respondto these small particles. that can also cause localinflammation, can cause reactions of tissuewhich also lead to pain. this is one of the biggestproblems in design of hips. one of the reasons they'vegotten better is that people have gotten better about makingmaterials that resist this kind of wear.that's why they last for 20
years now instead of 10 years asthey did in the past. there are newer kinds ofmaterials that people are beginning to create.they're new in a variety of ways.one of the ways they're new is that they don't require as muchbone cement any longer. this acetabular cup forexample, is made of a ceramic which is very porous and whichsticks to bone more naturally and more easily than the oldmetal cups used too. another difference in thisdesign, is instead of having a
metal head which moves againstthe--a metal ball which moves against the polymer socket,this one has a ceramic head. the friction between ceramicand a polymer is even less then the friction between a metal anda polymer. these are also much lighter,ceramics are lighter, they're very strong.you can create a joint that lasts even longer with materialslike this. engineers are continuouslymaking improvements in the materials that go into jointslike this.
they're making improvements inthe design to make them easier for surgeons to implant.now, a total hip replacement, putting these pieces into apatient takes only about an hour in the operating room,which is remarkable given the amount that has to happen duringthat time. i want to quickly reviewsome other kinds of artificial materials.i'm going to talk for just a minute about something that wetalked about before; dialysis for kidney failure.it's an example of what's
called an extracorporeal bloodtreatment, meaning that blood--'extra' means outside,'corporeal' means body, 'extracorporeal' is outside thebody. you take the blood outside ofthe patient, you pass it through a device, the treatment device,and then it goes back into the patient.you know, you saw in section what a dialyzer unit looks like.it's an example of a treatment where blood is passed throughsome kind of a device, something happens to the blood,something good happens,
and then the blood is returnedto the patient. a dialyzer might look likethis, there's blood that comes into a chamber and that bloodflows through many, many different hollow fibers.so, blood flowing through these fibers.on the outside of the fibers you're flowing a second solutioncalled the dialysate. molecules, waste molecules likeurea which are inside the blood capillaries diffuse out into thedialysate, they're removed from the blood.blood with a high concentration
of urea comes in this side,blood with lower urea comes out this side and goes back to thepatient. that urea is removed by thedialysate that goes around the hollow fibers.well, what if you changed this design slightly and askedit to do something different? instead of just flowing in asolution of saline or a balanced salt solution that was designedto pull urea out of the blood, what if you put cells in thearea around these hollows fibers?what if you put cells in?
what if they were cells fromthe pancreas, for example?now, blood is flowing through this hollow fiber just likebefore. on the outside there's not justa solution of salt, but there are cells from thepancreas. what if this membrane workedthe same way it does in dialysis?it allows for small molecule weight molecules to go through.then, if blood came in and it had sugar in it,that sugar would diffuse out
into the fluid in the shell,what we used to call dialysate. if blood sugar is high andthese are cells from the pancreas, what do cells of thepancreas do when they see high concentrations of blood sugar?they secrete insulin. that insulin would be secretedand it would flow back through the tube into the blood.you could make potentially an artificial pancreas this way,that was used to treat blood outside the body.a diabetic patient, blood comes out,it goes through this device.
glucose would stimulate thecells to secrete insulin, the insulin would go back intothe blood, and the insulin would be returned to the body.if these pancreas cells worked properly, they would respondjust like a normal pancreas does: when sugar goes up,insulin goes up, sugar goes down,insulin goes down. it does that automaticallybecause the cells are responding to the glucose.that would be very inconvenient;it might be a good solution but
it would be inconvenient ifyou're--had diabetes and you needed this all the time to betaking the blood out of the body and you'd have this device thatyou'd have to carry around with you.what if you made it so you could implant it totally insidethe body as well? that's what this diagram showshere. here's an example of thatdialysis unit that is--dialysis like unit but it's made to bevery small. you can see the shell,the outside shell here is a
clear plastic.it's about the size of--smaller than a hockey puck but not a lotsmaller than a hockey puck. there's a tube that comesin that brings blood in, there's a tube that comes outand brings blood out. this tube goes in and then itwraps around several times inside and then it goes back outand that wrap--those coils of tubing that around inside areall surrounded by cells from the pancreas.if you hook this up inside the body such that you have bloodgoing in one side and then
coming out the other,then you've created a device that potentially could treatdiabetes automatically and continuously,as long as the cells were alive inside this shell.this was in the design of a--what's called a bio-hybridpancreas. it's made of syntheticmaterials, the kind of materials we've been talking about,polymers. it's filled with live cellsthat are harvested from a pancreas.now, because there's a
material that separates thecells from your body, unlike in tissue engineeringwhere we wanted the cells to integrate into the body,now there's a material that separates the cells.so, i don't have to use cells that are immunologically matchedwith a patient, they're separated.in fact, i don't even have to use human cells.i could use cells from another animal, as long as they respondto sugar and make insulin that works in the patient.so, you might be able to use
cells from a pig and create anartificial pancreas that works in a person.these designs were made almost 20 years ago now and they workfairly well. there are several problems thatstill have not been solved. one is that the cells don'tlive forever. we know from cell culture theproblem with maintaining cells outside the body.here, you would like cells that last for a very long period oftime and continue to secrete insulin.they don't last for long enough
for this to be an effectivetherapy in people yet. a device that is similar tothat, the same kind of idea, is used to treat patients thathave severe liver disease. now, you might think about animplantable device like that, but unlike the pancreas,a device that replaced the functions of your liver,we talked about all the different functions of yourliver. to make an artificial devicelike that pancreas that provided all the functions of your liverwould need a lot of liver cells,
and it would have to be prettybig. people aren't yet thinkingabout an implantable device for liver.what they do use it, though, is for--as a device tosupport the function of patients.if this a patient who has a diseased liver,they're waiting for a liver transplant,how can you keep them alive without a functioning liver,during the time when they're waiting for a transplant toarrive?
what some hospitals are nowusing are devices in which pig liver cells are suspended in ahollow fiber reactor, very much like a dialysis unit.the patient is on something like dialysis,but dialysis that not only removes waste products,dialysis that provides liver function as well,because inside this unit are liver cells or hepatocytes thatare performing all the functions that liver inside your bodywould perform. this is another example of anartificial organ.
an artificial organ that'sused in many thousands of times around the country everyday isthis unit here called a heart/lung bypass orcardiopulmonary bypass machine. this machine can replace thefunction of your lungs and your heart during an operation.if surgeons need to operate on your heart, they can hook you upto this machine instead. they can stop your heart,your own heart and then this machine will take over thefunctions of both your heart and your lungs.how does it do that?
it does that because there's apump, a mechanical pump. there's blood being removedfrom the body and from the venous side, this is blood thatneeds oxygen. it's being pumped at the normalcardiac output through a device that oxygenates it.the pumps replace the function of your heart;the oxygenater replaces the function of your lungs.blood is pumped through the oxygenater;it goes from being oxygen-poor, carbon dioxide-rich,to being carbon dioxide-poor,
oxygen-rich and then goes backinto your body. you can remain on a pump likethis for several hours while the surgeon does a heart transplant,replaces your heart, while the surgeon does a valvereplacement. while the surgeon replaces acoronary artery, for example.this machine can keep your--can basically serve as an artificialheart and lungs during surgery. of course,one of the things that you would like to do is be able todo something like this but to
totally replace the function ofthe heart and have a--this is only valuable when you're in theoperating room. it requires an extensive andtalented team to operate it to keep you alive.what has been a goal of biomedical engineers,for many decades, is to design an artificialheart that could be totally implanted and could replace thefunction of your heart when your heart begins to fail.we're not there yet. there are still problems.what this slide shows you
is some of the designs that havebeen tested over time. this is an early design,not of an artificial heart but of an artificial ventricularassist device. this is a device that'ssupposed to give your ventricle an extra boost when it needs itif you're heart is failing and your normal cardiac muscle isn'table to create the force to get your blood pressure and flow uphigh enough. you can read more about this inthe book. these two are cartoons thatshow you what was called the
jarvik heart,the jarvik-7 heart, which was implanted in a numberof patients and still used in some clinical centers around theworld when a patient's own heart has failed and they're waitingfor a heart transplant. the surgeons will sometimesmake the decision, the patients not going to livewithout some kind of support for their heart function.they'll put an artificial heart in just to keep them aliveduring the period when they're hopefully waiting for a heart tocome.
this is the most recent ofthose. this is the abiocor heart.this made of the same kinds of materials we've talking about,made of polymers. a very smooth reliable pump ina very small form that can be hooked up to your normalvasculature and take over the function of the heart.many of the problems that have been largely solved up tothis point here is to develop materials that could be incontinuous contact with blood and not have the kinds ofclotting or other reactions that
could cause problems if you usethis kind of device in a person. those problems have,not entirely, but largely been solved.the major problem with an artificial heart now is how topower it. producing all this mechanicalenergy that's required to pump blood and keep your bloodpressure high requires energy. so, all of these hearts have anexternal power source with them. there are cables that come frominside the patient outside to a system of batteries that powerthe heart.
it's not possible yet to makethat power source small enough that it could be convenientlyeither implanted or worn by the patient for chronic use.that's one of the biggest problems with the design of thisparticular artificial organ now. we'll meet this afternoonin section, course review and please come with questions.as i mentioned, i'll have some materialprepared to just describe what's covered--what we've covered inthe last half of the course on the final.it's been a pleasure.
thanks.
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