BENG 100: Frontiers of Biomedical Engineering
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Frontiers of Biomedical Engineering
BENG 100 - Lecture 25 - Biomedical Engineers and Artificial Organs
Chapter 1. Introduction to Biomaterials [00:00:00]
Professor Mark Saltzman: So, today I’m going to continue to talk about applications of Biomedical Engineering, so as sort of a way to bring together some of the concepts that we’ve talked about over the last several months. Tuesday, I focused on applications in cancer. We thought about how imaging techniques, how instruments that deliver radiation, how molecules and cells could be used to treat cancer. Today we’re going to–the focus is going to be on artificial materials. Biomaterials, which are widely used in medicine now and were produced largely through the work of material scientists and chemical engineers, and biomedical engineers over the last 100 years or so. We’ll talk about some of the difficulties with creating a material that can be implanted in the body, and we’ll talk about some of the applications of those materials, 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 to replace tissues that are lost for one reason or another, is not new. The one picture here shows a remarkable discovery from a mummy that is something like 3,000 years old. This particular mummy was a woman 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 people have probably tried to use the materials that were in the world around them to replace parts of the body that were lost to trauma 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 what I think is a remarkable material. This clear part here is a lens that’s actually implanted into the eye. It’s like a contact lens but it’s permanently placed inside the eye over your natural lens. This is for people that have very severe difficulty in vision, because the properties of their natural lens have changed. So, you can put an artificial material, so it’s made of a polymer, inside the eye. It can stay there for the rest of their lives restoring their vision to near normal and requiring no other effort on their part. They don’t have to put in the contact lens everyday, because it’s there inside their eye all the time.
Chapter 2. Polymers [00:03:15]
What kinds of materials are these that we can use now to replace or restore the function of tissues that are damaged? Well, many of the materials that are used, most commonly, and with the most success now are polymers or plastics. We’ve talked about some different aspects of polymers and medicine throughout the course here. What I wanted to show you on this slide is–and again not that you would memorize or even be able to read all the details here, but there are a large number of different synthetic materials that now are produced and regularly used in medical applications.
Polymers, as you know, are manufactured products. Most of them are made from products that are derived from petroleum or oil. They’re organic molecules, typically small units that are polymerized together to form long chains. Because the individual molecules in a polymer are long chains, when you put a bunch of them together in a material, they entangle together and they give you a nice material property. You’re not falling down to the ground now because the plastic chairs that you’re sitting on are quite strong. This polymer material that makes 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 of wood they would be very heavy. These are quite light, you can pick them up easily. If they were made out of metal they would be much heavier, they might be stronger but they would be much heavier. One of the advantages of polymer materials is that you can make things that have quite a 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 do with quite a large degree of sophistication over the last 100 years or so. You can make many different kinds of polymers, now, that differ in the chemistry of the monomers that are linked together to make these long chains. You can, of course, change the length of the chain. You can make materials that are made up of polymers that have very long chains or shorter chains. As you could imagine, that changes properties, like the material property of elasticity that we talked about a few weeks ago.
We’ve discovered, mainly through a process of trial and error, that many of these materials are biocompatible. That is, you can put them in contact with tissues of the body, and the side effects of implanting that material are not severe. Now, in a few slides I’m going to tell you more about how the body responds to biomaterials. What you’ll see is that the response 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 the application that you want to use it for, has the right properties for the application, and also has the right extent of compatibility in the tissue you want to use it in. This is just to show you kind of the range of materials that can be used now in some of the applications 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 last week was making tubes of polymers, tubes of polymers that can be used to replace the conduits through which blood flow. This slide shows you some examples of arterial grafts, so synthetic materials that are used to replace a segment, let’s say of the aorta. This might be needed because the patient has had some kind of trauma where their aorta has become ruptured like in a car accident, for example. It’s deep within your body so it would have to be a pretty significant trauma in order to hurt your aorta. More commonly, sometimes there are diseases of the aorta where the wall of the aorta 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 a medical emergency.
If you diagnose those early enough then you can replace that segment of the aorta with a synthetic polymer. This has been done for decades now, there are several different materials that can be used in this way. Because the aorta is a large caliber vessel it stays patent, that is the blood can flow through continuously for many decades. This is true for vessels that are larger than say 5 mm in diameter. As the size goes down, it becomes more difficult to use synthetic materials in these applications. You can’t use a synthetic material 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’t work in smaller diameter vessels in a few moments.
Most of the materials that are used here were initially developed for other purposes. The two most common materials that are used in conduits like this are Dacron, which is a synthetic polymer that was first–was used for lots of things but it’s made into clothing, for example. Surgeons like it because it has nice properties, you can sew it easily. Imagine that a material that’s going to be used in an application like this, a surgeon has to be able to sew into it fairly readily. It has to be able to hold a suture, and that suture line has to make a neat connection or anastomosis 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’re familiar with called GORE-TEX. GORE-TEX is basically Teflon, its Teflon that is treated in a special so that it becomes porous. One of the properties of Teflon, you use it as cookware, for example, because things don’t stick to it. It’s not a sticky polymer, it’s fairly inert to particularly proteins that might stick on the surface. On it’s own, it would not be porous and so it wouldn’t allow any molecules to pass through. GORE-TEX, on the other hand, is fashioned–and this is a picture of GORE-TEX at very high magnification here, so it has small pores in it. Pores that are so small that a droplet of water can’t pass through, but molecules of water can. That’s why GORE-TEX is so useful as a material for hiking for rain gear, it allows water to evaporate through it but doesn’t allow drops of water to go in. You can make a waterproof material that still allows your body to sweat and for vapors to come off your body but doesn’t allow water to go in. That same property makes it useful for arterial grafts as well. There’s some facts on this slide that show you how many of these operations that use these kinds of materials are performed every year.
Another example of using synthetic materials like that is in the heart valve. We talked about how heart valves function several weeks ago. We talked about how your heart becomes very inefficient in its pumping 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 heart valves would stop working. Their heart, even though it was beating properly, could not deliver the flow 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 a heart 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 ring underneath 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 down below this here. If there was pressure on this side, it would force the ball up. When the pressure in the left ventricle got to be higher than the aorta, it would force the ball up. Then, flow would go out because the ball sitting in this position completely seals the opening.
When the pressure pushes the ball up then it opens up a pathway around it, so blood can come out through the sides and the ball goes up but it doesn’t go away because it’s constrained by this cage on the top. Now, when the pressure here gets higher than the pressure down here, the ball falls back down and it reseals. So, it does exactly what we wanted or what we described the heart valve is doing, that is opening up when the pressure difference was right, when the pressure was higher in the ventricle then the aorta, and then closing again when the pressure in the aorta was higher than the ventricle.
Now, the problem with this is you remember how the normal valve opens, it opens like a doorway. The normal valve opens like a doorway, so the part that’s shut totally opens. There’s a very clear path for flow. In this kind of a ball valve, the ball is still in the way. The fluid has to go around the ball 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 additional resistance. Your heart has to work harder in order to overcome the resistance of the flow going around this large ball that’s in the center.
It works well as a valve but it’s not a very efficient valve, in that it requires your heart to work more to get a certain flow rate because it’s blocking–this ball is blocking the center of the flow. In addition, you can imagine this ball slamming up and then slamming back 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 sensitive to mechanical forces. Everytime this valve opens and closes 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 the 1970s, it’s this valve that’s shown here. In many ways it’s similar, it has the same kind of a textile ring and metal on the outside. Now it’s shown sort of end-on, so you’re looking through the valve and what you don’t see here are two, what are called leaflets. These are made of metal and they fold like this, close like this and then they open like that. It’s more like a swinging door and also responds to pressure because it can only open one way. It goes like this; it won’t go like that, so it only opens in one direction in response to a pressure drop and then it closes in the other way. This is now the most commonly used design for a totally synthetic valve.
Still, a popular valve that’s used are these two valves that are shown here. This is one is from a cow, this one is from a pig, and they’re natural valves that are recovered from the animals. Then, they’re treated, they’re cross-linked with a chemical so that they become permanent structures, non-living structures now. These sort of bio-synthetic valves, what’s called in the caption here, a bio-prosthesis. Prosthesis just means replacement, so this is derived from natural tissue is an alternative to this mechanical valve. Physicians will use one of these types of valves or another depending on which of your valves needs replacement, what their own experience is with people that have diseases like the ones they’re treating. There are at least several options available.
Chapter 3. Threat of Coagulation and Clotting [00:15:50]
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 called coagulation or blood clotting. Of course, this natural reaction is important to our lives. If you damage a blood vessel, the blood vessel becomes ruptured. 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 flowing through a nice tube that has a very consistent endothelial cell lining, it’s now exposed to the tissue outside when the blood vessel gets ruptured. When it’s exposed to the tissue outside, a series of chemical reactions gets initiated.
That series of chemical reactions is called the coagulation cascade. It involves proteins that are also enzymes that go from an inactive state to an active state. This is described in the book in some detail. I’m not going to ask you questions about the molecular details of this. I want you to just sort of understand the concept, that a protein in the blood gets activated by exposure to a foreign surface. It creates an activated enzyme, which then activates another enzyme, 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 a cross-linked network called fibrin. Exposure to a foreign surface sets off a series of chemical reactions. The end result is that a natural protein in your blood that’s normally dissolved and just flowing around in your blood called fibrinogen gets cross-linked into a gel or semi-solid material. This is the formation of a clot.
Now, when this reaction happens, this cross-linking of fibrinogen into fibrin happens, they’re usually cells that are trapped there as well because these cross-linking reactions occur in blood and there’s lots of blood that gets cross-linked into this network. You form a semi-solid structural material that seals off 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 a chemically 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 of it 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 valve in the blood pathway, this clotting reaction will start to happen. That’s what’s shown in this slide here. You can’t see it too well but this surface would ordinarily look smooth. It doesn’t look smooth because there are proteins coagulated on the surface here. These proteins of fibronectin that are being converted into a fibrin gel. There are also specialized cells that also find these fibrin networks, and they spread out to help form a barrier. These cells are called platelets, and you know platelets are also important in blood clotting reactions.
One of the problems with every synthetic material that’s used to replace a component of your 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 few hours of when the heart valve is replaced. Then doesn’t happen anymore because it becomes a sort of natural 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 are used as heart valves, is that they have to be able to support 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 and eventually, since there’s blood flowing by, pieces of that clot could be expelled from–or detached from the 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 and cut off blood flow to that region. That process is called embolism. Embolism is when a small particle is released into your bloodstream, and embolism can cause 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 the skin. What you see is that after time this unusual layer of tissue forms, this is called a part of the foreign body reaction. Your body tries to form a kind of scar around the material. I’ll show you how that happens in a cartoon in just a minute. Materials that are very–that are not so inert can cause extensive cellular reactions like the one I show on the bottom here. These dots here are cells from your inflammatory system. They’re neutrophils and macrophages that are collecting at the site of the foreign material. The material here was a mesh and you can see where the fibers of 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 would say these cells are coming in as part of the inflammatory response, as part of the unwanted response to this material.
Chapter 4. Physical Responses to Biomaterials [00:22:22]
Every material produces a different reaction when you put it into the body. The details of the reaction depend on the chemistry of the material, its mechanical properties, how its surface is treated, if the surface is rough or smooth. From an engineering perspective, those are all things that we can potentially change. We can design materials hopefully 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 general characteristics. There’s general ways that your body responds to all materials and those general ways are shown in this cartoon.
In the first few minutes, seconds, or up to an hour, when you put a material into the 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 with blood, 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 the abundant proteins that are naturally abundant in blood like albumin and fibrinogen, other kinds of proteins like that. Protein absorption happens very quickly.
Within the next few days cells will start to accumulate around the material. It appears that–what we know now suggests that these cells are recruited to the material because of the proteins that are absorbed. You can understand that–you know that proteins are–surround all the cells in our body. We talked about extracellular matrix and how there are concentrated 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 will stick to it.
Now, the first cells that arrive and that stick are cells of the inflammatory response. In the inflammatory responses, the natural process of your body 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 for something potentially bad to happen. Then when it does, they try to start the healing process. These cells recognize that proteins are attached to the material and they begin to accumulate at this site here. The first cells that arrive are neutrophils, the second set are macrophages.
Now, those are the cells that I show accumulating at high concentration around this material here. What they do is they start the healing process and they do that in a variety of ways. One is that they release enzymes that try to digest whatever is around. They also send out signals to recruit other kinds of cells to come in. That’s what’s shown in this second stage here, is that the cells condense into a layer. They form what are called giant cells, which are basically macrophages that fuse together to form a giant cell, which in some circumstances can completely 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 healing whatever is happening at this local site. ‘
If this was a splinter, for example, that you got underneath your skin your body’s response to it would be to form a scar all the way around it and to try to digest it. If you’ve ever had a splinter that you couldn’t get out you might have waited for a few days, or a few weeks. Eventually, the splinter gets covered with some kind of a tissue and it comes up towards the top of your skin and eventually gets ejected from your body. That’s one kind of a healing response that’s natural. If that splinter was too deep it would just get totally covered with a scar, scar all around it. The cells that are in the scar tissue would be secreting enzymes and digestive chemicals inside trying to dissolve the splinter. If it was made of wood, eventually it would dissolve and it would completely disappear.
If it’s made of a synthetic polymer that doesn’t respond–or doesn’t get digested by those chemicals what happens is that a stable 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 different levels of response like this. Some of the responses are very mild 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 of cellular tissue that would form around the outside. Some responses are mild and those are considered biocompatible, and some are more vigorous and those are considered to be not so compatible. It happens with almost every material we know.
Chapter 5. Joint Replacement Using Biomaterials [00:27:41]
Let’s talk for a few minutes about a completely different kind of application. Again, this one that I mentioned a few weeks ago when we were talking about biomechanics, and that is replacement of the hip. I just showed you this drawing here 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 talked about in class and in section a few weeks ago. If there’s a disease of this bone and this needs to be replaced, then the general procedure now is to replace not only 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 a material that you put into the socket, and a material that you put onto the femur to fit into that socket.
I showed you this picture before 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 that metal ball inside that socket, that doesn’t work so well. Metal on metal, there’s some friction between these two. If this was a motor and you had metal on metal, you’d put oil in between there to lubricate. This is not possible in this situation. You put something else in there to lubricate and the something else is this white material. It’s a layer of polymer, a thin layer of polymer that also forms a cup, fits exactly into this acetabulum piece. The ball of the femur, then, is gliding on this smooth polymer piece. These polymer pieces have been made of a variety of different materials over the years, Teflon, and now most of the pieces now are made of high density polyethylene. Bobby?
Professor Mark Saltzman: Modern hip replacements, and I’ll show you some new designs, now typically have a lifetime of closer to 20 years. I’ll tell you why many of them have to be replaced after about 10 years, the older designed ones. Design has gotten better over time with these, and I’ll talk about some of the ways that it’s gotten better.
One of the problems is that this piece here, this ball of the femur, this part that’s going to replace the hip has to be very firmly attached to the rest of your–to the rest of the bones of your leg, to your femur. If you’re standing on one leg, all the weight of your body is really being carried by this piece of material here. That’s why they’re made out of metal because metals are strong and 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 too elastic. 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’s a long piece here that goes down into the bone and this long piece that goes into the bone allows you to fix the ball of the femur to the rest of the femur. It’s fixed because this metal part down here goes down into the shaft of your femur, and then is held there. It’s kind of like a long, thick nail that goes down into the length of the bone and what you hope is that that large surface area in contact, metal to bone, holds the whole piece into place so that the hip operates smoothly.
Now, one of the goals of this would be to create a design that naturally integrates into your bone and, what’s called on this, a ‘self-locking mechanism’. What would a self-locking mechanism be like? Well, maybe you’d put holes in this material like the holes shown here so that your bone could grow through it. As your bone heals around this implant 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–not perfect, 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 period before that happens. What is usually done is that another material is used to lock these materials temporarily in place. That material is called bone cement; it’s a polymer that can be polymerized when you shine light on it. It’s not too dissimilar from the materials that’s dentists use now to fill cavities. If you had a cavity filled recently they put some sort of a material into the cavity and then they shine a light on it. They put on the goggles and they cover up your face and they shine a light on it. The polymer that they put into the cavity polymerizes and forms a hard surface. Here, they put the polymer all around the acetabular cup, they put the polymer into the recess that they push the bone into. Then, they shine light on it so that it starts to–so that it polymerizes and hardens and forms a very tough material that fixes this thing in place. That’s called bone cement and the material is polymethylmethacrylate.
You can see that this now involves at least three different kinds of materials. There’s the metal that’s used to make the implant, there’s the polymer lining that’s used to lubricate the joint between the two metals, and there’s the other kind of polymer, the cement that’s used to 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 found out that their hip wasn’t working so well anymore. They were starting to get pain from their hip joint or they weren’t able to move it through the whole range of motion that they 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 the poly–or the Teflon cup, there was enough friction where the Teflon would start to wear. It would start to wear down and it would get thinner and thinner over time. Eventually, as in this case with this particular patient, could totally disappear. If it disappeared then you’ve got metal on metal now, harder to move your hip, probably causing pain when you move it as well because the pieces aren’t lubricated as well.
In addition, what happens is that when this metal is moving against the polymer, it wears down but the polymer doesn’t vanish, it has to go somewhere. What most people think is happening is that tiny particles of the Teflon or the polyethylene are being created locally. As wear happens, you’re wearing down the material, you’re creating many small particles of the material that are released. Those particles, then, can start an inflammatory response. Your body will start to respond to these small particles. That can also cause local inflammation, can cause reactions of tissue which also lead to pain. This is one of the biggest problems in design of hips.
One of the reasons they’ve gotten better is that people have gotten better about making materials that resist this kind of wear. That’s why they last for 20 years now instead of 10 years as they did in the past. There are newer kinds of materials 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 much bone cement any longer. This acetabular cup for example, is made of a ceramic which is very porous and which sticks to bone more naturally and more easily than the old metal cups used too.
Another difference in this design, is instead of having a metal head which moves against the–a metal ball which moves against the polymer socket, this one has a ceramic head. The friction between ceramic and a polymer is even less then the friction between a metal and a polymer. These are also much lighter, ceramics are lighter, they’re very strong. You can create a joint that lasts even longer with materials like this. Engineers are continuously making improvements in the materials that go into joints like this. They’re making improvements in the design to make them easier for surgeons to implant. Now, a total hip replacement, putting these pieces into a patient takes only about an hour in the operating room, which is remarkable given the amount that has to happen during that time.
Chapter 6. Dialysis [00:38:01]
I want to quickly review some other kinds of artificial materials. I’m going to talk for just a minute about something that we talked about before; dialysis for kidney failure. It’s an example of what’s called an extracorporeal blood treatment, meaning that blood–‘extra’ means outside, ‘corporeal’ means body, ‘extracorporeal’ is outside the body. You take the blood outside of the 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 through some kind of a device, something happens to the blood, something good happens, and then the blood is returned to the patient.
A Dialyzer might look like this, there’s blood that comes into a chamber and that blood flows through many, many different hollow fibers. So, blood flowing through these fibers. On the outside of the fibers you’re flowing a second solution called the dialysate. Molecules, waste molecules like urea which are inside the blood capillaries diffuse out into the dialysate, 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 the patient. That urea is removed by the dialysate that goes around the hollow fibers.
Well, what if you changed this design slightly and asked it to do something different? Instead of just flowing in a solution of saline or a balanced salt solution that was designed to pull urea out of the blood, what if you put cells in the area around these hollows fibers? What if you put cells in? What if they were cells from the pancreas, for example? Now, blood is flowing through this hollow fiber just like before. On the outside there’s not just a solution of salt, but there are cells from the pancreas. What if this membrane worked the 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 and these are cells from the pancreas, what do cells of the pancreas do when they see high concentrations of blood sugar? They secrete insulin. That insulin would be secreted and 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 the cells to secrete insulin, the insulin would go back into the blood, and the insulin would be returned to the body. If these pancreas cells worked properly, they would respond just like a normal pancreas does: when sugar goes up, insulin goes up, sugar goes down, insulin goes down. It does that automatically because the cells are responding to the glucose.
That would be very inconvenient; it might be a good solution but it would be inconvenient if you’re–had diabetes and you needed this all the time to be taking the blood out of the body and you’d have this device that you’d have to carry around with you. What if you made it so you could implant it totally inside the body as well? That’s what this diagram shows here. Here’s an example of that dialysis unit that is–dialysis like unit but it’s made to be very 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 lot smaller than a hockey puck.
There’s a tube that comes in that brings blood in, there’s a tube that comes out and brings blood out. This tube goes in and then it wraps around several times inside and then it goes back out and that wrap–those coils of tubing that around inside are all surrounded by cells from the pancreas. If you hook this up inside the body such that you have blood going in one side and then coming out the other, then you’ve created a device that potentially could treat diabetes 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-hybrid pancreas. It’s made of synthetic materials, the kind of materials we’ve been talking about, polymers. It’s filled with live cells that are harvested from a pancreas.
Now, because there’s a material that separates the cells from your body, unlike in tissue engineering where 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 matched with 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 respond to sugar and make insulin that works in the patient. So, you might be able to use cells from a pig and create an artificial pancreas that works in a person. These designs were made almost 20 years ago now and they work fairly well. There are several problems that still have not been solved. One is that the cells don’t live forever. We know from cell culture the problem with maintaining cells outside the body. Here, you would like cells that last for a very long period of time and continue to secrete insulin. They don’t last for long enough for this to be an effective therapy in people yet.
Chapter 7. Artificial Organs and Conclusion [00:43:51]
A device that is similar to that, the same kind of idea, is used to treat patients that have severe liver disease. Now, you might think about an implantable device like that, but unlike the pancreas, a device that replaced the functions of your liver, we talked about all the different functions of your liver. To make an artificial device like that pancreas that provided all the functions of your liver would need a lot of liver cells, and it would have to be pretty big. People aren’t yet thinking about an implantable device for liver. What they do use it, though, is for–as a device to support 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 to arrive? What some hospitals are now using are devices in which pig liver cells are suspended in a hollow 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 that are performing all the functions that liver inside your body would perform. This is another example of an artificial organ.
An artificial organ that’s used in many thousands of times around the country everyday is this unit here called a heart/lung bypass or cardiopulmonary bypass machine. This machine can replace the function of your lungs and your heart during an operation. If surgeons need to operate on your heart, they can hook you up to this machine instead. They can stop your heart, your own heart and then this machine will take over the functions of both your heart and your lungs.
How does it do that? It does that because there’s a pump, a mechanical pump. There’s blood being removed from the body and from the venous side, this is blood that needs oxygen. It’s being pumped at the normal cardiac 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 back into your body. You can remain on a pump like this for several hours while the surgeon does a heart transplant, replaces your heart, while the surgeon does a valve replacement. While the surgeon replaces a coronary artery, for example. This machine can keep your–can basically serve as an artificial heart and lungs during surgery.
Of course, one of the things that you would like to do is be able to do something like this but to totally replace the function of the heart and have a–this is only valuable when you’re in the operating room. It requires an extensive and talented team to operate it to keep you alive. What has been a goal of biomedical engineers, for many decades, is to design an artificial heart that could be totally implanted and could replace the function 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 have been tested over time. This is an early design, not of an artificial heart but of an artificial ventricular assist device. This is a device that’s supposed to give your ventricle an extra boost when it needs it if you’re heart is failing and your normal cardiac muscle isn’t able to create the force to get your blood pressure and flow up high enough. You can read more about this in the book.
These two are cartoons that show you what was called the Jarvik heart, the Jarvik-7 heart, which was implanted in a number of patients and still used in some clinical centers around the world when a patient’s own heart has failed and they’re waiting for a heart transplant. The surgeons will sometimes make the decision, the patients not going to live without some kind of support for their heart function. They’ll put an artificial heart in just to keep them alive during the period when they’re hopefully waiting for a heart to come. This is the most recent of those. 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 in a very small form that can be hooked up to your normal vasculature and take over the function of the heart.
Many of the problems that have been largely solved up to this point here is to develop materials that could be in continuous contact with blood and not have the kinds of clotting or other reactions that could cause problems if you use this 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 to power it. Producing all this mechanical energy that’s required to pump blood and keep your blood pressure high requires energy. So, all of these hearts have an external power source with them. There are cables that come from inside the patient outside to a system of batteries that power the heart. It’s not possible yet to make that power source small enough that it could be conveniently either implanted or worn by the patient for chronic use. That’s one of the biggest problems with the design of this particular artificial organ now.
We’ll meet this afternoon in section, course review and please come with questions. As I mentioned, I’ll have some material prepared to just describe what’s covered–what we’ve covered in the last half of the course on the final. It’s been a pleasure. Thanks.
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