INTRODUCTION

Polymers are the most important and largest family of materials being used in medical technology. Various polymers being used in conventional medical technology and surgery include Polyvinyl Chloride, Polyethylene, Polypropylene, Polystyrene, Polycarbonate, Acetal copolymers, Polybutylene terephthalate, Polyethylene terephthalate, a variety of Liquid crystal polymers and some specialised polymers synthesised through biotechnology route. Applications of polymers in medicine and surgery: -

Intracorporeal Materials Temporary devices: -

Surgical dressings Sutures Adhesives Polymeric intermedulary nails Polymer - fiber composite bone plates

Simple semipermanent devices: -

Tendons Reinforcing meshes Heart valves Joint reconstruction & bone cement Tubular devices Soft-tissue replacement materials for

cosmetic reconstruction. Drug delivery implants.

Complexdevices simulatingphysiological processes: -

Artificial kidney/Blood dialysis Artificial lung/Blood oxygenator Artificial pancreas/Insulin delivery system Artificial heart

Paracorporeal or extracorporeal materials: Catheters Blood bags Pharmaceutical containers Tubing Syringes, Surgical Instruments, etc.

The materials requirement for the above biomedical applications vary markedly according to the application being considered. The most important factor in selection of biomedical materials is for their biocompatibility. A biomaterial may be biocompatible in one application for a specific purpose, but not in a similar application at a different site. Therefore, specifications of biocompatibility must include the conditions of use and evaluation. One of the major problems encountered with artificial organs is blood compatibility since many of these organs either handle blood directly (heart, blood vessels) or come into contact with the blood in a membrane exchange reaction (kidney, lungs, etc.)

For a polymer to be used in biomedical device, it must have the appropriate mechanical properties. The polymer must be available in reproducibly pure form. It must have a good fabrication and must be stable enough that it should not be adversely affected by the normal physiological environment. Above all biomedical polymers (including additives and degradation products) should not exhibit toxic or irritant qualities.

Many biomedical applications require polymer systems with unique properties, for such as diffusion delivery properties in membranes dialysis, drug applications,

oxygenators and biodegradable applications, including sutures and some drug delivery systems. Numerous polymeric systems have been explored for use in cardiovascular systems. For example the materials used in artificial heart studies include Polyvinyl Chloride (PVC), silicone rubber (silatic), Polyurethane, Biomer and polyolefin rubber. However among polyurethanes the most promising materials appear to be some of the polyether urethane ureas. Artificial kidney is another example of an interesting development in the field of biomaterials. Artificial kidney is often referred to as haemodialysis unit, which removes waste products from the blood with polymeric semipermeable membrane. Which purifies the blood against artificial liquids in
4

a process known as hemodialysis or peritoneal dialysis. In peritoneal dialysis, silicone elastomer or polyurethane elastomer is generally used as caterers to access the peritoneal cavity A polyester cuff surrounds the segment of each catheter. In haemodialysis, the dialyser is normally made of several thousand hollow polymer fibers mounted in a polyurethane potting. The dialysis tubing is generally made of PVC. The membranes used are generally based on cellulose or cellulose derivatives.

Many of the other biomedical applications of polymers involving implants are related functions that do not have direct blood contact as occurs with artificial organs and thus do not have problems in terms of blood compatibility. Nevertheless these applications have certain specific requirements and problems. Polymers for wound dressings and/or artificial skin must have the flexibility and permeability of natural skin and also be able to maintain these features for a long time period. A major use of plastics in surgery is to replace soft tissue such as prosthetic breast, testicles etc. The major polymer used here is poly (di-methylsiloxane). Synthetic Polymeric wound dressings such as silicons; polyurethanes, polyvinyl chloride or polyethylene have made their appearance in the market recently. They are generally
5

thin layer films, which have a synthetic adhesive as a coating on the inner surface that adheres well to dry skin at the wound margins but does not adhere to the wound site. Recently natural polymers such as collagen, fibrin, fibronectin, alginate and hyaluronic acid have been studied as dressings for dermal wounds. Innovative polymer applications will contribute

significantly to the rapid development of future medical technology. Key drivers will be microsystem technology, minimally invasive surgical procedures and also dispersing and packaging systems, which thanks to their easy handling help the patient, comply with the physicians prescription. This scenario requires the development of problem-solving products that can only be realised with high-performance polymers. Present advances in materials science and biotechnology and rapidly blurring the line between the worlds of synthetic and biological polymers and their applications.

Furthermore, synthetic polymers are being designed to minic, either structurally or functionally as biological polymers. Some of the recent developments in polymers as materials for biomedical devices include: Transparent Devices: -

In many applications the plastic parts have to be transparent. Blister packs are one such example. Medicines whose packaging must show very good barrier properties can be made from a crystal clear film of cyclo-olefin copolymer. It supersedes the conventional polymers used in such applications. During in-patient and outpatient care, tube lines containing number of multi-way cocks or stopcocks and metering mechanisms are used for supply of most diverse liquids. For this a plastic is necessary which is transparent, and has very good chemical, fat and lipid stability. Amorphous PET has been developed to fulfil these requirements. Now-a-days glass has been replaced by plastics in most of the labwares used in medical research. The advantages of using plastics in Labwares such as Tissue culture plates, Tissue culture flask, Cryogenic vials, tissue culture tubes, centrifuge tubes, elisa plates, micropipette tips and petridishes is based on their high precision, low weight, low cost and little care in handling. Modifications in commodity plastics such as polypropylene, polystyrene and polycarbonate have made it possible to fabricate labwares of desired transparency and surface properties.

Degradable Polymers: Polymers like poly (lactides), poly (glycolides) and their copolymers have excellent properties and have thus been
7

developed for the applications such as wound closure, osteosynthesis, nets for support while wound is healing, degradable bandages and surgical cord for reinforcement, hollow fibres for treatment of damaged nerves as well as prostheses for anastomoses. For example a biodegradable intravascular stent prototype is molded for the from a blend of of polylactide and trimethylene treatment of carbonate. Furthermore these polymers are being considered development products for the paradontal diseases, fillers for tooth extraction, artificial vessels and drug carrier systems. Why would a medical practitioner want a material to degrade? There may be a variety of reasons, but the most basic begins with the physicians simple desire to have a device that can be used as an implant and will not require a second surgical intervention for removal. Besides eliminating the need for a second surgery, the bidegradation may offer other advantages. For example, a fractured bone that has been fixated with a rigid, non biodegradable stainless implant has a tendency for refracture upon removal of the implant while, an implant prepared from biodegradable polymer can be engineered to degrade at a rate that will slowly transfer load to the healing bone.

Advances in polymers for biotechnology are numerous. Now polymers have gone to the extent that the difference between synthetic and biological polymers has reduced to a great extent. Genetic engineering methods are being used to produce structures "artificial" and proteins with a range of designed synthesis functions. Traditional polymer

techniques are being coupled with biochemistry to produce materials that interact and control biological systems and cells. Various new fields have emerged that club the role of polymer chemistry with biotechnology. Environmentally responsive polymers for

biotechnological applications. Biological production of polymers (e.g.,

polystyrene, polyesters). Biopolymers and protein polymers. Polymers modified with biological -signals (e.g. adhesion peptides growth factors). Bioactive, biomimetic, and bioinspired polymers. Supramolecular assemblies in biotechnology. Polymers in analytical biotechnology. Polymers scaffolds for tissue engineering. Biopolymer surfactants. Polymer and surface modification of tissue culture. Cell polymer interactions. Polymers for drug delivery and artificial organs.

Vinyl in Medical Applications: No other plastic in existence today has the combination of performance qualities that vinyl has. Because of this, vinyl makes it possible to provide exceptional patient care while controlling healthcare costs. Vinyl medical products have been proven safe and effective worldwide, which is why vinyl is the leading medical plastic in use today. For example: Clarity and transparency: Because of its physical properties, products made from vinyl can be formulated with excellent transparency to allow for continual monitoring of fluid flow. If a color-coded application is needed, virtually any color of the rainbow is available. Flexibility, durability and dependability: Not only does vinyl offer the flexibility necessary for applications such as blood bags and IV containers, but it can also be relied upon for its strength and durability, even under changing emperatures and conditions. Sterilizability: Vinyl products can be easily sterilized using such methods as steam radiation or ethylene oxide. Compatibility: Vinyl is compatible with virtually all-pharmaceutical products used in healthcare facilities today. It also has excellent water and chemical resistance, helping to keep solutions sterile. Resistance to chemical stress cracking.

10

Vinyl's

resilience

helps for

assure

that

medical in

product

consistently applications.

function

extended

use

demanding

Ease of processing: Vinyl can easily be extruded to make IV tubing,

thermoformed to make "blister" packaging or blow molded to make rigid hollow containers. This versatility is a major reason why vinyl is the material of choice for medical product and packaging designers. Recyclability: Thanks to a significant investment on the part of the vinyl industry to develop automated sortation technology, vinyl products can be, and are being, recycled. Pilot programs show promise for recycling non-infectious vinyl medical waste, as well. Low cost: The use of vinyl plays a big role in containing rising healthcare costs. With vinyl accounting for over 25 percent of medical plastics currently in use, a switch to an alternative could cost the healthcare community hundreds of millions of dollars. Vinyl medical products play a leading role in hospitals, providing unmatched versatility and security to medical professionals. Life-giving blood and critical intravenous fluids are packaged in clear, flexible vinyl bags that extend the shelf

11

life of blood products and are easily monitored. Pliable vinyl tubing can be shaped to any requirement, Helping doctors direct care to wherever it needs to be delivered. Vinyl's ease of processing makes it a key player in other hospital products, too. It can be extruded, blow-molded or thermoformed to create a wide variety of applications, from bedpans to blister packs.

Vinyl's portability and ease of disposal make it an ideal choice for materials used in nursing homes and home-health care settings. Vinyl allows medical professionals to bring reliable care directly to the patient, and sterile, disposable single-use vinyl medical products help limit the possibility of infection. Vinyl products also help make these highly individualized types of care more affordable.

No other single material offers vinyl's unique combination of attributes: -

Clarity and transparency Flexibility, durability and dependability Sterilizability Product integrity Compatibility

12

Resistance to chemical stress cracking Ease of processing Recyclability Recoverability Cost-effectiveness This wide array of benefits makes vinyl the ideal material for medical applications.

Vinyl is used in hundreds of medical products and devices with more applications continually being developed. Some of the most prevalent uses include:

Blood bags And tubing Cannulae Caps Catheters Connectors Cushioning products Device packages Dialysis equipment And tubing

13

Drainage tubing Drip chambers Ear protections Examination gloves Goggles Inflatable splints Inhalation masks

Iv containers And components Labware Masks Mouthpieces Oxygen delivery Seals Surgical wire Jacketing Thermal blankets Valves.

14

Timeline: This timeline shows the chain of research that led to an understanding of polymers and the development of some of their medical uses. 1839 Charles Goodyear invents the process of vulcanization, which makes rubber into a dry, tough, springy material. 1858 Chemists Friedrich Kekul and Archibald Couper show that organic molecules are made up of carbon atoms combined chemically into different shapes. 1870 John Wesley Hyatt markets celluloid, a plastic made of chemically modified cellulose, also called cellulose nitrate.

15

1887 Count Hilaire de Chardonnet introduces a way to spin solutions of cellulose nitrate into Chardonnet silk, the first synthetic fiber. 1909 Leo Baekeland creates Bakelite, the first completely synthetic plastic. 1920 Hermann Staudinger proposes that polymers are long chains of smaller units that repeat themselves hundreds or thousands of times. He later receives a Nobel Prize for his research on the synthesis and properties of polymers. 1920s Kurt Meyer and Herman Mark use x-rays to examine the internal structure of cellulose and other polymers, providing convincing evidence of the multiunit structure of some molecules.

Late 1920s Wallace Hume Carothers and his research group at DuPont synthesize and develop applications for synthetic polyesters, neoprenes, and nylons. 1930 Germans develop two types of synthetic rubber (Buna-S and Buna-N) from butadiene, a petroleum byproduct. 1930s Paul Flory develops a mathematical theory to explain the creation of polymer networks "in which polymer fluids form cross-links and become, like rubber, elastic." Flory would
16

receive a Nobel Prize for his lifetime contributions to polymer chemistry in 1974. 1940s Peter Debye develops a light-scattering technique for measuring the molecular weight of large polymers. 1953 Karl Ziegler discovers catalysts for polymerization of ethylene. Giulio Natta synthesizes polypropylene. Their discoveries were recognized by a Nobel Prize. 1963 Edward Schmitt and Rocco Polistina file a patent for the first absorbable synthetic sutures, made of polyglycolic acid, a key plastic in tissue engineering. 1975 Robert Langer and M. Judah Folkman use polymers to isolate chemicals that stop the formation of blood vessels, suggesting a new way to attack cancer. These studies also establish the feasibility of controlled release of macromolecules.

1986 Langer and Joseph Vacanti demonstrate that liver cells grown on a plastic framework can function after being transplanted into animals, opening the door to the new field of tissue engineering.

17

1996 The U.S. Food and Drug Administration approves polymer wafer implants for treating brain cancer. 1997 Clinical trials show that artificial skin can heal diabetic skin ulcers, establishing the potential clinical feasibility of tissue engineering.

POLYMER USE IN PROSTHETICS

18

The use of polymers in the production of biomaterials (materials used in place of bone, tissue, etc) is widespread. Further examination into the unique properties of polymers and the requirements of artificial materials in living systems reveals the usefulness of polymeric biomaterials.

Requirements of Biomaterials: Biomaterials must be lightweight and structurally sound. The idea behind limb replacement and the insertion of any artificial body part is to offer a prosthetic that is comparable to the original part in function, structure, and weight. Biomaterials must be inert. They must be undetectable to the to the body, insuring acceptance and compatibility with the immune system. Biomaterials must be non-degradable. This property is necessary to prevent small microscopic particles of the inducing havoc materials from drifting throughout the body

else where. Non-degradability is also important to make sure that the material has a long life time in the body.

19

The Suitability of Polymers: Polymers are characteristically light weight. Their low density makes them great for use as biomaterials. (Think of how easy it is to move those white plastic lawn chairs. Sometimes they move too easily, such as when they slip out from under you when you sit down too quickly. Now imagine moving a rod iron chair of equivalent size. This is a great proof for the "weightlessness of polymers.) Polymers are very structurally sound. The flexibility and the strength of polymeric materials is a property unique unto itself. This property of being rigid and flexibility and the further flexible at the same time is similar to the

rigidity of the structural components of our bodies. (A reveals that

understanding of the molecules which compose our bodies they are polymers. That is why synthetic flexibility and rigidity.) The also called polymers can best mimic their

insertion of bonds between polymeric molecules,

cross-linking, allows the chemist to divine the rigidity of flexibility of the polymer. The more cross-linked a polymer is the greater is its rigidity. Most polymeric biomaterials are inert and non-toxic. In other words, these synthetic polymers don't react with the body. On the molecular level, most polymers lose their ability to react because their functional groups, place Polymers have become ideal materials for artificial organs because of their huge range of physical properties. Scientists can determine what type of material they need and then they can produce a particular polymer to fit that need. When found, the artificial organ must be first tested in vitro, in a test tube, and then in vivo, in the body.
20

Although polymers seem to be ideal for artificial organs because they can be tailor-made, they also are one of the biggest problems scientists face. These materials sometimes either damage the body, or the body eventually damages them. When searching for a polymer to be used, scientists must ask a few basic questions: 1) Is it the right polymer for the particular job? 2) Is it pure? Any residue from manufacturing of the polymer must be removed. 3) Can it be shaped into the right form without any change in its properties? 4)Can it be sterilized without changing its properties? For example, steam is usually used but it may melt or chemically degrade some polymers. 5) Will the polymer create clots or damage blood? Will it cause inflammation or tissue change?
21

Research is being carried to replace organs such as the liver, bladder, pancreas, kidneys, lung, and heart.

Due to the high numbers of people suffering from heart problems, this is where most research is taking place. There are many companies that manufacture various parts of the heart for artificial replacement. For example, many of these companies manufacture various types of valves made of materials such as silicon, pyrolitic carbon, Teflon, and Dacron. The polymers Teflon and Dacron are widely used in this field. Dacron is a polyester, most commonly formed from diols and diacids. A diol monomer reacts with a diacid monomer to form a polyester: HO------OH + HOOC------COOH = ------COO-----Teflon is a polymer made from the monomer tetrofluoroethylene C2F4. The problems faced with artificial hearts include clotting, blood damage, failure of man made materials (polymers) to perform in the body, and difficulty in getting a simple, safe, workable power source.

22

Teflon and Dacron are also used for artificial blood vessels. These materials are woven into vessels to replace large clogged arteries. These become coated with fibrous protein tissue in the blood in order to discourage clots. Some of these artificial vessels can last up to 15 years. This type of vessel can sometimes cause clotting if they are too small in diameter. This is because the flexibility between the polymer is different from that of the real vessel. In the case of smaller vessels, copolyurethanes are sometimes used. This material can pulsate better with the real vessel it is attached to.

Polyurethanes contain an amide-ester linkage and can be formed from a diisocyanate and a diol. Depending on what groups are contained in each monomer, the polyurethane can be glassy and tough or as in this case, very elastic. The polyurethane is then reacted with another monomer to produce a copolyurethane. The task of trying to decide what type of material is needed for these organs is sometimes as difficult as producing the particular polymer itself.

23

SYNTHETIC BIODEGRADABLE POLYMER SCAFFOLDS

In the medical field there has been a great surge in interest for the ability to engineer tissue as a route to enhanced healing with tissues that are genetically the same as the host body. Biotechnology has reached a point where cells can be cultured and grown but succesful delivery and subsequent growth of these tissues in-vivo has been stymied by the lack of suitable matrix for growth. In most cases the engineered tissues cannot be simply injected into an organism but require a solid support that not only provides a place for growth but possibly enhances growth and upon development of the tissue biodegraded leaving the selfsupporting tissue in place.

Much work has been done to utilize synthetic biodegradable polymers in this type of application and is a fascinating area of composite engineering. It is critical then to choose appropriate materials for this type of endeavour.

24

The materials must follow the follo wing criteria in order to be used in this application. Biocompatible: the material should not inducce an immune response in the host Biodegradable: the material should be completely

resorbable yielding only natural tissue

Moldable: the material should be easily molded into a variety of shapes with a certain amount of structural integrity Supportive: the material should provide mechanical support in order to yield space for the tissue to form and differentiate and if possible enhances growth and differentiation.

25

The materials used thus far and the most extensively can be viewed

SEM image of chondrycytes seeded on a PGA scaffold. The rod like shapes are the polymer fiber and the dots are cultured chrodrycyte cells

26

All of these materials have thus far proven useful with respect to many of the criteria mentioned above including formability, biodegradability and biocompatibility. Also the microstructure of these materials can provide ideal matrices for cell delivery and growth as pictured ABOVE.

Polymer Use in Artificial Skin The Basic Role of Polymers in Artificial Skin Growth. Artificial skin is a combination of human skin cells and biodegradable polymers. A three-dimensional polymer matrix acts as a template or scaffolding on which the dermal cells grow. The exact process by which the cells grow is not presently known. It seems the cells simply need the right environment and conditions to grow. The polymer matrix provides this environment as well as giving the skin shape. The matrix is bilayered so that the artificial skin can function much like real human skin. The underlayer is porous and designed to allow the ingrowth of human dermal cells. The outer layer is entirely synthetic and designed as a barrier against infection, water loss, and ultraviolet light. Human dermal cells taken from neonatal foreskin are seeded onto the polymer matrix. The cells adhere to the matrix and are then allowed to incubate for several weeks. During this time the cells multiply and organize themselves into functioning tissue.

27

Types of Polymers Used in Artificial Skin. Polymers used in artificial skin must be biocompatible so that the body won't reject the tissue. There has been a lot of research in this area. Biodegradable polymeric matrices made of a polyether/polyester copolymer and also of poly-L-lactide have been tested in animals for biocompatibility.1 This is done by surgically implanting a small piece of the matrix under the skin of the animal, and then observing the animal for possible reactions to the material. These polymers did not produce any negative effect in the animals and seem promising for use in humans. Research has also been done on the use of copolymers made of both natural and synthetic components. Researchers at MIT have been successful in using collagen glycosamino glycan copolymers to produce artificial skin. Researchers at Virginia Tech have been investigating the use of cellulose, the most abundant natural polymer in the world, in making artificial skin. Strength is another consideration for polymers used in artificial skin. The end product must be very durable even though it is made in very thin sheets. One type of temporary skin replacement contains a matrix made up of interwoven silicone and polytetrafluoroethylene. This gives the matrix both strength and flexibility. Polytetrafluoroethylene more commonly known as Teflon is well known for its strength and durablility. Teflon is made from the chain growth
28

polymerization of the monomer CF2=CF2 to make polymer of the form [-CF2-CF2-]n .

Applications of Artificial Skin and Current Products. Currently artificial skin has only been approved for use in the treatment of severe burn victims. If burn wounds are not treated quickly, the body attempts to close the wound be contraction. This can lead to painful and even disabling scarring. Real human skin for grafting is not always available, and often must be grown from the patient's own cells. This can take several weeks. Artificial skin is used as an interactive bandage to cover the wound until real skin grafts can be used to cover the wound. The artificial skin interacts with the body tissue to promote healing. There are several products that are currently approved for this use. Advanced Tissue Sciences in La Jolla, CA has developed "Dermagraft-TC"2. This product is made of a polymer membrane seeded with human cells. "Dermagraft-TC" is grown on a nylon mesh and then frozen. Freezing kills the cells, but leaves the tissue matrix and cell growth factors intact. This promotes growth of tissue around
29

the wound. Integra Life Sciences has developed "Integra Artificial Skin" a product made of a dermal layer and a synthetic polysiloxane epidermal layer.3 In this case the dermal layer interacts with the patients own cells. 7-14 days after the artificial skin has been applied, the synthetic epidermal layer is removed and real skin is grafted over the wound. Another product currently in use is " Original Biobrane",

a bandaging product which consists of a nylon matrix covered with a gelatin that promotes clotting factors in the wound. 3 Nylons can be formed by step growth polymerization in which a diacid is combined with a diamine. For example octanedioc acid can be polymerized with ethylene diamine to form Nylon 2,8. HOOC-(CH2)6-COOH + H2N-(CH2)2-NH2 = [-NH-(CH2)2-NH-C=O(CH2)6-C=O-]n The Future of Artificial Skin. Research and testing are currently being done with biopolymers and cultured skin cells to develop artificial skin
30

that can be approved for use as permanent skin grafts. Ideally this tissue will be grown and stored, so that it is readily available for use. Artificial skin is also being developed for use in the treatment of pressure sores resulting from long-term hospitalization, diabetic skin ulcers, and venous stasis ulcers.

PANCREAS:Pancreas is an artificial islet cell--a "smart membrane" device that senses blood glucose levels and in response releases insulin from a reservoir encapsulated by the membrane. Each of these design concepts is potentially useful; the one that ultimately succeeds in practice will be the one that is easiest to make, most reliable, and most durable under the actual conditions of use. The wide choice material used for this purpose is a polymer.

WOUND CARE & ARTIFICIAL TEETH

A semi-IPN based tetrafluoroethylene and silicone is used as a wound dressing material. The fluoropolymer provides support and reinforcement for the silicone, which is soft and pliable. The combination of the two biocompatible materials yields a film that is very flexible and tough. A picture of it is shown below. The material can be made into thin (15-750 microns) films, which allow oxygen and moisture to diffuse through the

31

material. Thus the material is "breathable", which is important in wound care applications. IPNs can be designed to absorb mechanical energy if one component is a rubbery material (low Tg) and the other is a rigid, glassy material (high Tg). When these two materials interpenetrate, you generate an interphase that has a glass transition temperature between that of the two components. This is important for energy absorption because, generally speaking, polymers absorb the most energy when they are near their glass transition temperature. If the two components can be made semicompatible, as is the case in an IPN, you end up with a material that can show a glass transition spanning over 100C range. This is a pretty dramatic effect that can easily be seen with dynamic mechanical analysis..

ARTIFICIAL TEETH:polymethylmethacrylate are used as artifical teeth. Artificial teeth can be made of porcelain or polymers. Polymers are much tougher than porcelain and resist chipping. A problem with polymers such as crosslinked PMMA is that certain foods (like salad oil) can plasticize the material, which severely decrease mechanical properties. Homo-IPNs of

32

methylmethacrylate swell less than crosslinked polymers and therefore aren't plasticized as easy.

TEMPORARY SCAFFOLDS:
Temporary scaffolds are used in circumstances where a region of natural tissue has been damaged by disease, injury, or surgery and requires artificial support. Ideal temporary scaffold provides support until natural tissues heal; as the tissue heals, the temporary scaffold should gradually degrade (and stresses are transferred from the temporary scaffold to the natural tissue) - examples are: sutures bone fixation devices (e.g., bone nails, screws, or plates),

CONTACT LENSES-

33

(2-hydroxyethyl methacrylate HEMA) is still the most widely used material for contact lenses - oxygen can diffuse through hydrogel lenses unlike hard contact lenses - wetting of the eye is derived from hydrogel lenses (use of hard contact relies on tearing to keep the eye moist) - disadvantages include lower durability, need for better hygienic maintenance, and the inability to be used for astigmatic correction

CARDIOVASCULAR REPLACEMENTS:POLYMERIC Biomaterials are used in many blood-contacting devices. vascular These grafts, include artificial heart valves, synthetic ventricular assist devices, drug-release

systems, extracorporeal systems, and a wide range of invasive treatment and diagnostic systems. An important issue in the design and in selection the of materials of the is the hemodynamic For example, conditions vicinity device.

mechanical heart valve implants are intended for long-term use. Consequently, the hinge points of each valve leaflet and the materials must have excellent wear and fatigue resistance in order to open and close 80 times per minute for many years after implantation. In addition, the open valve must minimize disturbances to blood flow as blood passes from the left ventricle of the heart, through the heart valve, and into the ascending aorta of the arterial vascular system.

34

To this end, the bileaflet valve disks of one type of implant are coated with pyrolytic carbon, which provides a relatively smooth, chemically inert surface. This is an important property, because surface roughness will cause turbulence in the blood flow, which in turn may lead to hemolysis of red cells, provide sites for adventitious bacterial adhesion and subsequent colonization, and, in areas of blood stasis, promote thrombosis and blood coagulation. The carbon-coated holding ring of this implant is covered with Dacron mesh fabric so that the surgeon can sew and fix the device to adjacent cardiac tissues. Furthermore, the porous structure of the Dacron mesh promotes tissue integration, which occurs over a period of weeks after implantation. While the possibility of thrombosis can be minimized in bloodcontacting biomaterials, it cannot be eliminated entirely. For this reason, patients who receive artificial heart valves or other blood-contacting devices also receive anticoagulation therapy. This is needed because all foreign surfaces initiate blood coagulation and platelet adhesion to some extent. Platelets are circulating actively cellular components in blood of blood, two and to four micrometers in size, that attach to foreign surfaces and participate coagulation thrombus formation. Research on new biomaterials for cardiovascular applications is largely devoted to understanding thrombus formation and to developing novel surfaces for biomaterials that will provide improved blood compatibility. Synthetic vascular graft materials are used to patch injured or diseased areas of arteries, for replacement of whole segments
35

of larger arteries such as the aorta, and for use as sewing cuffs (as with the heart valve mentioned above). Such materials need to be flexible to allow for the difficulties of implantation and to avoid irritating adjacent tissues; also, the internal diameter of the graft should remain constant under a wide range of flexing and bending conditions, and the modulus or compliance of the vessel should be similar to that of the natural vessel.

These aims are largely achieved by crimped woven Dacron and expanded polytetrafluoroethylene (ePTFE). Crimping of Dacron in processing results in a porous vascular graft that may be bent 180 or twisted without collapsing the internal diameter. A biomaterial used for blood vessel replacement will be in contact not only with blood but also with adjacent soft tissues. Experience with different materials has shown that tissue growth into the interstices of the biomaterials aids healing and integration of the material with host tissue after implantation. In order for the tissue, which consists mostly of collagen, to grow in the graft, the vascular graft must have an open structure with pores at least 10 micrometers in diameter. These pores allow new blood capillaries that develop during healing to grow into the graft, and the blood then provides oxygen and other nutrients for fibroblasts and other cells to survive in the biomaterial matrix. Fibroblasts synthesize the structural protein tropocollagen, which is needed in the development of new fibrous tissue as part of the healing response to a surgical wound.

36

Occasionally, excessive tissue growth may be observed at the anastomosis, which is where the graft is sewn to the native artery. This is referred to as internal hyperplasia and is thought to result from differences in compliance between the graft and the host vessels. In addition, in order to optimize compatibility of the biomaterial with the blood, the synthetic graft eventually should be coated with a confluent layer of host endothelial cells, but this does not occur with current materials. Therefore, most proposed modifications to existing graft materials involve potential improvements in blood compatibility. Artificial heart valves and vascular grafts, while not ideal, have been used successfully and have saved many thousands of lives.

However, the risk of thrombosis has limited the success of existing cardiovascular devices and has restricted potential application of the biomaterials to other devices. For example, there is an urgent clinical need for blood-compatible, synthetic vascular grafts of small diameter in peripheral vascular surgery--e.g., in the legs--but this is currently impracticable with existing biomaterials because of the high risk of thrombotic occlusion. Similarly, progress with implantable miniature sensors, designed to measure a wide range of blood conditions continuously, has been impeded because of
37

problems directly attributable to the failure of existing biomaterials. With such biocompatibility problems resolved, biomedical sensors would provide a very important contribution to medical diagnosis and monitoring. Considerable advances have been made in the ability to manipulate molecular architecture at the surfaces of materials by using chemisorbed or physisorbed monolayer films. Such progress in surface modification, combined with the development of nanoscale probes that permit examination at the molecular and submolecular level, provide a strong basis for optimism in the development of specialty biomaterials with improved blood compatibility.

ORTHOPEDICDEVICES:Joint replacements, particularly at the hip, and bone fixation devices have become very successful applications of materials in medicine. The use of pins, plates, and screws for bone

38

fixation to aid recovery of bone fractures has become routine, with the number of annual procedures approaching five million in the United States alone. In joint replacement, typical patients are age 55 or older and suffer from debilitating rheumatoid arthritis, osteoarthritis, or osteoporosis. Orthopedic surgeries for artificial joints exceed 1.5 million each year, with actual joint replacement accounting for about half of the procedures. A major focus of research is the development of new biomaterials for artificial joints intended for younger, more active patients. Hip-joint replacements are principally used for structural support. Consequently, materials that possess high strength, such as metals, tough plastics, and reinforced polymer-matrix composites dominate them. In addition, biomaterials used for orthopedic applications must have high modulus, long-term dimensional stability, high fatigue resistance, long-term biostability, excellent abrasion resistance, and biocompatibility (i.e., there should be no adverse tissue response to the implanted device). Early developments in this field used readily available materials such as stainless steels, but evidence of corrosion after implantation led to their replacement by more stable materials, particularly titanium alloys, cobalt-chromium-molybdenum alloys, and carbon fiberreinforced polymer composites.

39

A typical modern artificial hip consists of a nitrided and highly polished cobalt-chromium ball connected to a titanium alloy stem that is inserted into the femur and cemented into place by in situ polymerization of polymethylmethacrylate. The articulating component of the joint consists of an acetabular cup made of tough, creep-resistant, ultrahigh-molecular-weight polyethylene. Abrasion at the ball-and-cup interface can lead to the production of wear particles, which in turn can lead to significant inflammatory reaction by the host. Consequently, much research on the development of hip-joint materials has been devoted to optimizing the properties of the articulating components in order to eliminate surface wear. Other modifications include porous coatings made by sintering the metal surface or coatings of wire mesh or hydroxyapatite; these promote bone growth and integration between the implant and the host, eliminating the need for an acrylic bone cement. While the strength of the biomaterials is important, another goal is to match the mechanical properties of the implant materials with those of the bone in order to provide a uniform distribution of stresses (load sharing). If a bone is loaded insufficiently, the stress distribution will be made asymmetric, and this will lead to adaptive remodeling with cortical thinning and increased porosity of the bone. Such lessons in structure hierarchy and in the structure-property relationships of materials have been obtained from studies on biologic composite materials, and they are being translated into new classes of synthetic biomaterials. One development is carbon fiber-reinforced polymer-matrix composites. Typical matrix polymers include polysulfone and polyetheretherketones. The

40

strength of these composites is lower than that of metals, but it more closely approximates that of bone.

SOME OTHER APPLICATIONS:-

POLYMER PDMS VALVES POLYURETHANES PGA, PLA & PLGA DEVICES POLYTETRAFLUORO ETHYLENE POLYETHYLENE PROSTHESES. PMMA CELLOPHANE

APPLICATION CATHETERS,HEART

VENTRICULAR DEVICES DRUG DELIVERY

HEART VALVES VASCULAR GRAFTS NEVER REPAIR. CATHETERS, HIP

FACTUR FIXATION DIALYSIS MEMBRANES

41

VARIOUS POLYMERS USED IN MEDICINE: The most popular types of plastics being used polyvinyl chloride (PVC). Applications include are

polyethylene (PE), polypropylene (PP), polystyrene (PS) and tubes and catheters, examination and surgeons' gloves, lab- ware, urine and blood collection items like tubes, intravenous kits, and syringes. The reason why plastics are used for so many medical products is because of their material characteristics. They are durable, lightweight, versatile and com- patible with other materials. They also provide economic benefits. Additionally, many plastics are flexible (in the case of bags and tubes), and they pos- sess specific properties that make them suitable for use with gases and liquids. They can be sterilized chemically or ther- mally, and as a packaging choice, plastics offer protection against contaminants. In the case of clear plastics, they also enable visibility of the product packaged and being delivered through tubing. The

42

following is a short list of some of the more common types of plastics and Plastics in the hospital Medical devices currently being used to help save lives in hospitals all around the globe.Polyethylene (PE) the key properties that make PE ideal for use in the medical sector are its clarity and ability to remain chemically unreac- tive. Popular uses of this material include waterproof sheets, bags, bottles, jars, examination gloves, tubing, caps and enclosures. Polypropylene (PP) Some of the more important characteristics of PP are the material's resistance to chemicals and high heat, as well as the fact that it is lightweight and stiff.

Common medical devices made from PP include test tubes, bottles, beakers, dishes and jars. Polystyrene (PS) In addition to being used in cafeteria and food applications (such as trays and plates), PS is also used for petri dishes, culture tubes, IV butterfly valves, bottles, beakers and filters. Polyvinyl chloride (PVC) PVC has many qualities that make it a good material for products used in hospi- tal environments. It is chemically inert, resistant to water and weather corrosion, and is a tough yet versatile material for processing. Medical devices made from PVC include catheters, tubes, gloves, IV bags, respirator masks, patient cards and ID bands. PVC is particularly valuable in the storage and delivery of red blood products. More specialized plastics find applications in
43

joint replacements, such as artificial hips and heart valves. Plastics have become an integral part of hospital life. From medical equipment to supplies and packaging, plastics are help- ing to save lives in emergency situations and to improve the quality of life in oth- ers. CELLOPHANE:Cellophane Often used in every day life to package our products or to keep our food fresh, cellophane is one of the most critical materials for the treatment of many kidney malfunctions. Cellophane is regenerated cellulose. It is in the form of a film; as opposed to rayon, which has the same properties yet is a fiber. Cellophane holds almost identical properties to the naturally occurring cellulose, it is regenerated for processing purposes. It has a typical chain length ranging from 2000 6000 angstroms (longer in fibers) and a molecular weight of varying widely from 300,000 to one million g/mol4.

Cellophane (regenerated Cellulose) was invented was invented by Jacques E. Brandenberger in 1908. In an attempt to develop a clear plastic cloth that was waterproof, he discovered that while his cloth that he produced was to stiff, a clear plastic film would be peeled off and soon known as cellophane5. While years later processes would seal the permeability of this regenerated cellulose and make it waterproof, the properties

44

the original material held would soon help save and prolong many lives. In 1959 Dr. Willem J. Kolffs first artificial kidney was installed in St. Pauls hospital in London. Ethical debate would continue for 2 years, but in 1961 the first dialysis was performed. Within 5 years a separate unit was opened in the hospital to treat patients suffering from renal problems. This machine used the idea of countercurrent flow, osmosis and diffusion to remove waste products from the blood stream, which are normally removed by the kidneys6. The first artificial kidney used vegetable parchment to serve as the separation membrane between the fluids, which would selectively remove the undesirables. Natural casings (i.e. intestines) were also used in the earlier stages of development of the artificial kidney. In the 1960s Brandenbergers original cellophane was put to use as the membrane that filters and separates the dialysis fluid from the blood. The precursor to the saran wrap that we use today had properties that are so desirable because of its ultra small permeability.Cellophane membranes that separate the fluids in dialysis machines are expected to be hydrophilic ultra filters, with the driving force being the concentration gradient between the two fluids. Many other properties are required between the fluids to make dialysis.

45

Most importantly the membrane permits many small particles in the blood with low molecular weights such as inorganic salts, urea, and creatine pass through the membrane while important components of the blood do not7. The production of cellophane as stated earlier is simply the regeneration of cellulose. Obtained naturally from wood and cotton fiber. Cellulose is reacted with NaOH and carbon disulfide to produce cellulose xanthate. Cellulose xanthate is then treated with sulfuric acid. The result of the reaction is extruded to a sheet and after a small aging period, a thin clear film of cellophane can be peeled. The process by which cellophane is known is viscose4. While early in history there were many concerns about potential health risks involved with cleaning a persons blood by a machine, debate quickly subsided with proof of effectiveness. Today dialysis machines save thousands of lives daily. The only true alternative to dialysis is kidney transplant. Even in the very unlikely case of a successful transplant (over 50% rejection rate) dialysis is continued for many month or years, to ensure stability. The future of cellulose membranes in the treatment of renal failure has no limits. Perhaps one-day membrane efficiency will be so effective, predictable, and controllable enabling an actual internal artificial kidney. The main inconvenience with dialysis is the actual administration of the lengthy procedure. With improvements in the engineering of the membrane in dialysis, the result has been healthier patients and longer lives for the unfortunate victims.

46

PGA, PLA, AND PLGA :The polymer polyglycolic acid, PGA, initially started out as an absorbable suture named Dexon. Dupont, under the direction of Norton Higgins, first synthesized PGA by a three-step process from glycolic acid by manipulating temperature and pressure. The ability of PGA to form biodegradable sutures, however, wasnt found until 1963 by Edward Schmitt and Rocco Polistina of the American Cyanamid Corporation. Since the birth of PGA, derivatives of this polymer have been found to have useful medical properties as well. Modifying the chemical and structural properties of PGA, PLA, and PLGA allows the polymers to be used for a wide variety of applications within the human body. These polymers are then used for drug-delivery systems, to construct synthetic scaffolding, etc. The amorphous form of PLA is used for drug delivery applications. The latest treatment in treating brain tumors involves attaching dime-sized wafers directly into the skull8. The wafers are made out of PLA or PLGA and slowly distribute cancer-killing reagents directly into the location where its needed. The more crystalline form of PLA has been found to useful as well. The mechanical toughness and strength of the semi crystalline form of PLA and PGA is exploited for use in orthopedic devices. Employing the polymers for the construction of 3-D scaffolding does this. The
47

scaffolding is then implemented to grow new tissues to replace damaged organs in the body. All the polymers have very low polydisperity index ratios, for example, the P.D.I. ratio for PLA is around 1.6-1.9. The low ratio is useful to maintain mechanical and structural consistency for later applications.

The most common method of commercial production of PLA and PGA is by utilizing ring-opening polymerization combined with an insertion mechanism using a metal oxide4. Depending on structure, the polymers can be fitted for different applications. A more amorphous form of the polymer can be used for drug delivery devices while the crystalline form is good for building scaffolding and other biodegradable structures. PLGA, for example, is completely amorphous so therefore it is used only in drug delivery devices. For scaffolding, a more crystalline form of polymer is useful. Two essentials in building scaffolding are having a high surface to volume ratio, and it has to be highly porous. This is advantageous since it allows to cells to easy proliferate and pathways for nutrients and metabolites. The cells are first grown in a culture, and then are seeded onto the scaffolding to grow the damaged organ9. The scaffolding gradually erodes away as cells began to grow and replace lost tissue around the

48

region. Using a lower molecular weight polymer can speed up degradation. PGA, PLA, and PGLA are new novel ways to treat a variety of medical concerns. There are some drawbacks, however, to their effectiveness. The use of certain drugs, for example, is prohibited by the relatively temperatures used in constructing these polymers. Another drawback is in the controlled release of drugs. Bulk erosion has a somewhat inconsistent release of drugs. Depending on the amount of drug loaded onto the polymer, the hydrophilic or hydrophobic properties, the initial rate of release can vary. These persistent problems are likely to be solved in the future. Due to recent legislation, which bars suppliers of ingredients of medical components from being sued, researchers and companies are freer to pursue medical applications and problems.

Polydimethyl siloxane The polymer polydimethyl siloxane (PDMS) is used in

pacemakers, the delivery of vaccines, and the construction cerebrospinal fluid shunts. PDMS is an amorphous structure with low cross-linked elasticity. As a vulcanized rubber it cannot be melted or dissolved. The glass transition temperature of PDMS is very low (150K), and the polymer is very permeable to gases. The low glass transition temperature allows for fast molecular relaxation, which is beneficial for molding applications. An English chemist, Dr. Frederic Stanley Kipping, discovered silioxanes in 1927. Kipping however, incorrectly analyzed the structure of his newly found macromolecule and as a result he called his discovery silicone. This name still persists today. It
49

wasnt until 1943, however, that mass production silicones occurred. General Electric started industrial production under the direction of Eugen Rochow. PDMS are used in numerous beneficial applications. For example, PDMS became an essential ingredient for use in glass eyes in World War 2. Prior to the inception of localized drug delivery within the human body, antigens had to be taken orally and it was difficult, if not impossible to simulate local immune response in the body. This principle of localized drug delivery using PDMS comes into play in radical prostatectomy and radiation therapy for treatment of prostate carcinoma. There are several complications due to the surgery the most significant complication is post operative incontinence, which affects 30% of patients10. Since PDMS stays localized in the injection site a lesser dosage of drugs is needed due to the increased concentration in the affected area. For the delivery of the vaccine, biodegradable pellets made of PDMS are used.

The pellets are very small in diameter and generally contain soluble antigens to be released within the body. The pellets consist of vulcanized rubber and have a mean diameter of 188 um which allows for the particles to stay in the localized region. Drug release is controlled by the relative magnitude of the velocity of macromolecular relaxation to the velocity of drug diffusion through the rubbery region.11. Also PMS isnt very susceptible to bacterial infection. This property also
50

makes it ideal for use in pacemakers and the construction of cerebrospinal fluid shunts where the chance for cancer becomes nil. One method for the production of dimethyl siloxane starts with the monomer, dichlorodimethylsilane. Hydroxyl groups, through hydrolysis, replace the two chlorines in the monomer. To achieve a higher molecular weight, however, a different approach is used. This new method is done by a base catalyzed ring-opening polymerization of the siloxanes.4. Most major producers of PDMS arent involved in the medical industry. PDMS is mainly found in worldly applications such as lubricants, foaming agents, etc. The main public concern for the use of PDMS stems from postoperative complications. Troubles in surgery usually start after the implanted device becomes contaminated with microorganisms or the wound becomes infected. Even under the most stringent antiseptics conditions, contamination is still a factor that has to be taken into account. Bacterial infection at the site of the catheter could occur for several reasons including surface adhesion and growth, production of extracellular components (slime), etc. PDMS, however, is still at the forefront of medical research, whose novel properties warrants further research.

POLYETHYLENE AND POLYMETHYLMETHACRYLATE (PMMA):51

Many common thermoplastics, such as polyethylene and polyester, are used as biomaterials. Thermoplastics usually exhibit and moderate to high tensile plastic strength at (5 to 1,000 strains. megapascals) with moderate elongation (2 to 100 percent), they undergo deformation high Depending on the structure and molecular organization of the polymer chains, thermoplastics may be semi-crystalline or highly crystalline. Joint replacements, particularity at the hip, and bone fixation devices have become very successful applications of materials in medicine. The use of pins, plates, and screws for bone fixation to aid recovery of bone fractures has become routine, with the number of annual procedures approaching five million in the USA alone12. Hip-joint replacements are principally used for structural support. Consequently, materials that possess high strength, such as metals, tough plastics, and reinforced polymer-matrix composites dominate them. In addition, biomaterials used for orthopedic applications must have high modulus, long-term dimensional stability, high fatigue be no resistance, adverse and tissue biocompatibility(i.e., there should

response to the implanted device). Early developments in this field used readily available materials such as stainless steels, but evidence of corrosion after implantation led to their replacement by more stable materials, particularly titanium alloys, cobalt-chromium-molybdenum alloys, and carbon fiberreinforced polymer composites. A typical modern artificial hip consists of a nitrided and highly polished cobalt-chromium ball connected to a titanium alloy stem that is inserted into the

52

femur and cemented into place by in situ polymerization of polymethylmethacrylate.

Consequently, much research on the development of hip-joint materials has been devoted to optimizing the properties of the articulating components in order to eliminate surface wear. Other modifications include porous coatings made by sintering the metal surface or coatings of wire mesh or hydroxyapatite; these promote bone growth and integration between the implant and the host, eliminating the need for acrylic bone cement13. POLYTETRAFLUOROETHYLENE: PTFE is thermosetting polymer very limited application in medicine, but its characteristic properties, which combine high strength and chemical resistance, are useful for some orthopedic and dental devices. It also has high modulus and tensile properties with negligible elongation. The polymer chains in this material are highly cross-linked and therefore have severely macromolecular mobility; this limits extension of the polymer chains under an applied load. Biomaterials are used in many blood-contacting devices. These include artificial heart valves, synthetic vascular grafts, ventricular assist devices, drug releases, and a wide range of invasive treatment and diagnostic systems. An important issue in the design and selection of materials is the hemodynamic
53

conditions

in

the

vicinity

of

the

device.

For

instance,

mechanical heart valve implants are intended for long-term use. Consequently, the hinge points of each valve leaflet and the materials must have excellent wear and fatigue resistance in order to open and close 80 times per minute for many years after implantation. In addition, the open valve must minimize disturbances to blood flow as blood passes from the left ventricle of the heart, through the valve and into the ascending aorta of the arterial vascular system. To this end, the bileaflet valve disks of one type of implant are coated with pyrolytic carbon, which provides a relatively smooth, chemically inert surface.

Synthetic vascular graft materials are used to patch injured or diseased areas of arteries, for replacement of whole segments of larger arteries such as the aorta, and for use as sewing cuffs. Such materials need to be flexible to allow for the difficulties of implantation and to avoid irritating adjacent tissues; also, the internal diameter of the graft should remain constant under a wide range of flexing and bending conditions, and the modulus or compliance of the vessel should be similar to that of the natural vessel. A biomaterial used for blood vessel replacement will be in contact not only with blood but also with adjacent soft tissue. Experience with different materials has shown that tissue growth into the interstices of the biomaterials aids healing and integration of the material with host tissue after implantation. In order for the tissue, which consists mostly of collagen, to grow in the graft, the
54

vascular graft must have an open structure with pores at least 10 micrometers in diameter. Fibroblasts synthesize the structural protein tropocollagen, which is needed in the development of new fibrous tissue as part of the healing response to a surgical wound. Artificial heart valves and vascular grafts, while not ideal, have been used successful and have saved many thousands of lives. However, the risk of thrombosis has limited the success of existing cardiovascular devices and has restricted potential application of the biomaterials to other devices. Considerable advances have been made in the ability to manipulate molecular architecture at the surface of materials by using chemisorbed or physisorbed monolayer films. Such progress in surface modification, combined with the development of nanoscale probes that permit examination at the molecular and submolecular level, provide a strong basis for optimism in the development of specialty biomaterials with improved blood compatibility14.

POLYURETHANE :Seen today in everyday uses such as shoe soles, tires and foams, polyurethane holds an extremely import role in cardiac medicine today. Polyurethane is a thermoset that is also a noncondensation step growth polymer4. Polyurethane has a very low molecular weight compared to many other polymers with a molecular weight average of only 47,000 g/mol. The benefits of this material lie in the basics of it visible physical properties. Polyurethane is often described to bridge the gap between
55

rubber and plastic. It holds one of the best load-bearing capacities of almost any materials around15. Invented back in 1937 by Otto Baker, polyurethane was the result of a search for a material that has high strength and good environmental resistance. For both reasons polyurethane today is one of the most important materials in use for ventricular assist devices. Differing from artificial hearts, VADs are for short-term assistance to cardiac circulation attached to one or both of the heart ventricles. Most commonly seen in the operating room during open-heart surgery, postoperatively, and in the cases of extreme cardiac trauma. They consist of tubing attached to the heart valves leading to a pump that can be centrifugal, electrical, or pneumatic. While Dr. D. Liotta of Baylor University developed the principles of this device in the 1950s, two doctors, Pierce and Donachy in 1971, significantly refined the technology. Rewriting the book on fluid mechanics (relating to blood flow) and taking advantage of polymers as a material. Polyurethane (segmented) stabilized the VAD, making not only the contact barrier of the blood and machine the safest possible, but also using the compressive properties that it exhibits made it function more like the actual heart itself. The once majority metal device was revealed in 1976 and approved for use by the FDA in 198016.

There are two ways to produce polyurethane. However, the most abundant source (95% of world production) is obtained
56

through step growth polymerization of diisocyanates with dihydroxl compounds. The result is a polymer that has a load bearing capacity comparable to cast steel. Polyurethane is molded most often through injection molding. Additionally as of recent years, reaction injection molding (RIM) has become one of the more popular ways to produce in industry. For the most polyurethane used for VADs are produced under careful supervision and not often RIM produced. The largest debate over the use of these materials was potential for mechanical failure. Past occurrences of failure have been attributed to poor processing and not the material itself17. VADs have made great strides in the past 20 years. Where once limited to external unit only, today there are internally placed VADs and as the technology improves, it may one day replace transplant surgery to cure cardiac conditions. While there are many types of VADs, the only material that is a true alternative in some sense to the polyurethane is stainless steel. Advancements in the use of ventricular assist devices can be seen in the decrease in number of deaths of patients awaiting transplant, even with a great increase of people on the waiting list. Perhaps not a solution, the temporary alternative that exists in VADs can only be attributed the integration of polymers into their design.

57

ELASTOMERS:Elastomers, which include rubber materials, have found wide use as biomaterials in cardiovascular and soft-tissue applications owing to their high elasticity, impact resistance, and gas permeability. Applications of elastomers include flexible tubing for pacemaker leads, vascular grafts, and catheters; biocompatible coatings and pumping diaphragms for artificial hearts and left-ventricular assist devices; grafts for reconstructive surgery and maxillofacial operations; wound dressings; breast prostheses; and membranes for implantable biosensors. Elastomers are typically amorphous with low crosslink density (although linear polyurethane block copolymers are an important exception). This gives them low to moderate modulus and tensile properties as well as high elasticity. For example, elastomeric devices can be extended by 100 to 1,000% of their initial dimensions without causing any permanent deformation to the material. Silicone rubbers such as Silastic, produced by Dow Corning, Inc., are crosslinked, so that they cannot be melted or dissolved--although swelling may occur in the presence of a good solvent. Such properties contrast with those of the linear polyurethane elastomers, which consist of soft polyether amorphous segments and hard urethane-containing glassy or crystalline segments. The two segments are incompatible at room temperature and undergo microphase separation, forming hard domains dispersed in an amorphous matrix. A key feature of this macromolecular organization is that the hard domains serve as physical crosslinks and reinforcing filler. This results in elastomeric materials that possess relatively high modulus and extraordinary long-term stability under sustained cyclic loading. In addition, they can be processed by methods common to thermoplastics.

58

POLYMERS & PHARMACEUTICALS:An example of polymer application is the utilisation of latex coatings is by the pharmaceutical industry, in the preparation of drug coatings, and industries where similar technology may be employed in dispersion systems that might previously have relied on the periodic addition of a chemical. Polymers have gained in importance in the pharmaceutical industry as both drug encapsulants and vehicles of drug carriage: either protecting an active agent during its passage through the body (or in storage by preventing moisture ingress) until its release, or controlling its release. A conventional (eg, sugar) tablet coating has the

disadvantageous side effect of delivering what may be an initially too high and, hence, harmful, dose of active agent (typically, drug is rapidly released from its dosage form, reaching a maximum concentration, which then decays exponentially until the next administration), to regions of the body where the drug may not be at its most effective; When the general aim of any medication is to generate a response in a specific area or organ of the body requiring treatment. These problems can be overcome to some extent by

59

sustained/retarded release, and/or selective delivery of the drug to the targeted organs. Advantages of controlled release devices thus possibly include: delivery to the required site; delivery at the required rate; fewer applications; reduced dangers of overdose, or side effects; and also economic advantages by virtue of more efficient dosage, at the expense of possibly more complicated fabrication. For example, on a specific type of polymer offering suitable transport characteristics for an individual permeant, or concentrates on a range of permeants transported through a single polymer type, or concentrates on a unique application.

In

recent

years, in

there

have carriers

been and

numerous controlled

developments

polymeric

release systems (some commercially available devices have been described by). A few examples mentioned include:

films with the drug in a polymer matrix (monolithic devices);

the

drug

contained

by

the

polymer

(reservoir

devices)];

polymeric colloidal particles or microencapsulates (microparticles, microspheres or nanoparticles) in the form of reservoir and matrix devices drug contained by a polymer containing a hydrophilic and/or leachable additive eg, a second polymer, surfactant or plasticiser, etc. to give a porous device,

60

or a device in which the drug release may be osmotically 'controlled' (both reservoir and matrix devices);

enteric coatings (ionise and dissolve at a suitable pH)

(soluble)

polymers

with

(covalently)

attached

'pendant' drug molecules,

BIO-MEDICAL APPLICATIONS OF POLYMERS INDEX 1. 2. 3. 4. 5. 6. 7. 8.

9.

INTRODUCTION VINYL IN MEDICAL APPLICATION POLYMER USE IN PROSTHESIS POLYMER USE IN ARTIFICIAL TEETH POLYMER USE IN WOUND CARE APPLICATION POLYMER USE IN ARTIFICIAL SKIN POLYMER USE IN CARDIOVASCULAR REPLACEMENT POLYMER USE IN ORTHOPEDIC DEVICES OTHER APPLICATIONS VARIOUS POLYMERS IN MEDICINE

10.

61

11.

POLYMERS & PHARMACEUTICALS

CERTIFICATE

This is to certify that mr. Shashank B. choudhary has sucessfully completed his project work on-

For the partial fulfillment of Msc-II year in the acadmic year

62

2001-2002

HEAD OF DEPT

63

64