Polymeric Biomaterials 2010

POLYMERIC BIOMATERIALS

Polymers (from the Greek: polys, many; meros. part or unit) are large molecules made up by the repetition of small, simple chemical units termed monomers. In some cases the repetition appears much as a chain is built up from its links. In other cases the chains are branched are interconnected to form three-dimensional networks. Polymers have found applications in every specialty area and continue to be the most widely used materials in health care. Polymers can be classified in several different ways according to their structures, the type of reactions by which they are prepared, their physical properties, or their technological use. The earliest and most frequent application of textile material for surgery is believed to be suture materials, used to close wounds. As early as 4 thousand years ago linen was used as a suture material. Later, natural fiber from the bark of trees, plaited horsehair, cottons and silk were also used. Due to the development of synthetic fibers like nylon, polyesters and polyolefins in the 1950s, synthetic fibers have gradually replaced natural fibers for wound closure purposes. Basic Structure Polymers have very long chain molecules which are formed by covalent bonding along the backbone chain. The long chains are held together either by secondary bonding forces such as van der Waals and hydrogen bonds or primary covalent bonding forces through crosslinks between chains. The long chains are very flexible and can be tangled easily. In addition, each chain can have side groups, branches and copolymeric chains or blocks which can also interfere with the longrange ordering of chains. For example, paraffin wax has the same chemical formula as polyethylene (PE) [(CH2CH2)n], but will crystallize almost completely because of its much shorter chain lengths. However, when the chains become extremely long {from 40 to 50 repeating units [CH 2CH2] to several thousands as in linear PE} they cannot be crystallized completely (up to 80 to 90% crystallization is possible). Also, branched PE in which side chains are attached to the main backbone chain at positions normally occupied by a hydrogen atom, will not crystallize easily due to the steric hindrance of side chains resulting in a more noncrystalline structure. The partially crystallized structure is called
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semicrystalline which is the most commonly occurring structure for linear polymers. The semicrystalline structure is represented by disordered noncrystalline (amorphous) regions and ordered crystalline regions which may contain folded chains as shown in figure below.

The polymer chains can be arranged in three ways; linear, branched, and a crosslinked (or three-dimensional) network as shown in figure below. Linear polymers such as polyvinyls, polyamides, and polyesters are much easier to crystallize than the cross-linked or branched polymers. However, they cannot be crystallized 100% as with metals. Instead they become semicrystalline polymers.

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Polymerization In order to link the small molecules one has to force them to lose their electrons by the chemical processes of condensation and addition. By controlling the reaction temperature, pressure, and time in the presence of catalyst(s), the degree to which repeating units are put together into chains can be manipulated. The degree of polymerization (DP) is defined as an average number of mers, or repeating units, per molecule, i.e., chain. Each chain may have a different number of monomers depending on the condition of polymerization. Also, the length of each chain may be different. Therefore, it is assumed there is an average degree of polymerization or average molecular weight (MW)

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The following factors influence the mechanical properties of polymers. 1. Composition. 2. Molecular weight, 3. Amount of unreacted monomer in the polymer, 4. Morphology (Structure), 5. Crystallinity. 6. Configurational structure 7. Additives. Polymers Used as Biomaterials
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1. polyolefin A polyolefin is a polymer produced from a simple olefin (also called an alkene with the general formula CnH2n) as a monomer. For example, polyethylene is the polyolefin produced by polymerizing the olefin ethylene. An equivalent term is polyalkene; this is a more modern term, although polyolefin is still used in the petrochemical industry. Properties Polyolefins are impossible to join by solvent cementing because they have excellent chemical resistance and can only be adhesively bonded after surface treatment because they have very low surface energies. They are also extremely inert chemically and exhibit decreased strength at lower temperatures. A more specific type of olefin is a poly-alpha-olefin (or poly--olefin, sometimes abbreviated as PAO), a polymer made by polymerizing an alpha-olefin. Many poly-alpha-olefins have flexible alkyl branching groups on every other carbon of their polymer backbone chain. These alkyl groups, which can shape themselves in numerous conformations, make it very difficult for the polymer molecules to line themselves up side-by-side in an orderly way. Therefore, many poly-alpha-olefins do not crystallize or solidify easily and are able to remain oily, viscous liquids even at lower temperatures.

2. polyamide A polyamide is a polymer containing monomers of amides joined by peptide bonds. They can occur both naturally, examples being proteins, such as wool and silk, and can be made artificially through step-growth polymerization, examples being nylons, aramids, and sodium poly(aspartate).Ex:

Production from monomers

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Polyamides are polymers where the repeating units are held together by amide links. The amide link is produced from the condensation reaction of an amino group and a carboxylic acid or acid chloride group. A small molecule, usually water, or hydrogen chloride, is eliminated. The amino group and the carboxylic acid group can be on the same monomer, or the polymer can be constituted of two different bifunctional monomers, one with two amino groups, the other with two carboxylic acid or acid chloride groups. Amino acids can be taken as examples of single monomer (if the difference between R groups is ignored) reacting with identical molecules to form a polyamide:

The reaction of two amino acids. Many of these reactions produce long chain proteins Aramid (pictured below) is made from two different monomers which continuously alternate to form the polymer and is an aromatic polyamide:

The reaction of 1,4-phenyl-diamine terephthaloyl chloride to produce Aramid.

(para-phenylenediamine)

and

3. Fluorocarbons

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Fluorocarbons, sometimes referred to as perfluorocarbons, are organofluorine compounds that contain only carbon and fluorine bonded together in strong carbonfluorine bonds. The electron withdrawing nature, or electronegativity, of fluorine results in many of the unique characteristics of fluorocarbons. For example, the electronegativity of fluorine makes single bonds to carbon remarkably strong. Resultingly, fluoroalkanes are more chemically and thermally stable than alkanes. However, fluorocarbons with double bonds (fluoroalkenes) and especially triple bonds (fluoroalkynes) are more reactive than corresponding hydrocarbons. Also, the electronegativity of fluorine also reduces the cohesive intermolecular forces of fluorocarbons by mitigating the effect of the London dispersion force. Fluoroalkanes can serve as oil-repellant/water-repellant fluoropolymers, solvents, liquid breathing research agents, and powerful greenhouse gases. Unsaturated fluorocarbons tend to be used as reactants, as fluorocarbons with double and triple bonds are not as stable 4. Silicone rubber Silicone rubber is a polymer that has a "backbone" of silicon-oxygen linkages, the same bond that is found in quartz, glass and sand. Normally, heat is required to vulcanise (set) the silicone rubber; this is normally carried out in a two stage process at the point of manufacture into the desired shape, and then in a prolonged post-cure process. It can also be injection molded. Silicone rubber offers good resistance to extreme temperatures, being able to operate normally from -55C to +300C. At the extreme temperatures, the tensile strength, elongation, tear strength and compression set can be far superior to conventional rubbers although still low relative to other materials. Organic rubber has a carbon to carbon backbone which can leave them susceptible to ozone, UV, heat and other ageing factors that silicone rubber can withstand well. This makes it one of the elastomers of choice in many extreme environments. Compared to other organic rubbers, however, silicone rubber has a very low tensile strength. For this reason, care is needed in designing products to withstand even low imposed loads. Silicone rubber is a highly inert material and does not
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react with most chemicals. Due to its inertness, it is used in many medical applications and in medical implants. However, typical medical products like breast implants and catheters have failed because of poor design. Structure

Silicone rubber chain Polysiloxanes differ from other polymers in that their backbones consist of SiO-Si units unlike many other polymers that contain carbon backbones. One interesting characteristic is an extremely low glass transition temperature of about -127C (Fitzpatrick 1999:428). Polysiloxane is very flexible due to large bond angles and bond lengths when compared to those found in more basic polymers such as polyethylene. For example, a C-C backbone unit has a bond length of 1.54 and a bond angle of 112, where as the siloxane backbone unit Si-O has a bond length of 1.63 and a bond angle of 130. 5. Polyvinylchloride (PVC) PVC is an amorphous, rigid polymer due to the large side group (Cl, chloride) with a Tg of 75~105C. It has a high melt viscosity hence it is difficult to process. To prevent the thermal degradation of the polymer (HCl could be released), thermal stabilizers such as metallic soaps or salts are incorporated. Lubricants are formulated on PVC compounds to prevent adhesion to metal surfaces and facilitate the melt flow during processing. Plasticizers are used in the range of 10 to 100 parts per 100 parts of PVC resin to make it flexible. Di-2-ethylhexylphthalate (DEHP or DOP) is used in medical PVC formulation. However, the plasticizers of trioctyltrimellitate (TOTM), polyester, azelate, and phosphate ester are also used to prevent extraction by blood, aqueous solution, and hot water during autoclaving sterilization. PVC sheets and films are used in blood and solution storage bags and

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surgical packaging. PVC tubing is commonly used in intravenous (IV) administration, dialysis devices, catheters, and cannulae. 6. Polyethylene (PE) PE is available commercially in five major grades: (1) high density (HDPE), (2) low density (LDPE), (3) linear low density (LLDPE), (4) very low density (VLDPE), and (5) ultra high molecular weight (UHMWPE). HDPE is polymerized in a low temperature (60~80C), and at a low pressure (~10 kg/cm 2) using metal catalysts. A highly crystalline, linear polymer with a density ranging from 0.94 to 0.965 g/cm3 is obtained. LDPE is derived from a high temperature (150~300C) and pressures (1,000~3,000 kg/cm2) using free radical initiators. A highly branched polymer with lower crystallinity and densities ranging from 0.915 to 0.935 g/cm3 is obtained. LLDPE (density: 0.91~0.94 g/cm3) and VLDPE (density: 0.88~0.89 g/cm3), which are linear polymers, are polymerized under low pressures and temperatures using metal catalysts with comonomers such as 1-butene, 1hexene, or 1-octene to obtain the desired physical properties and density ranges. UHMWPE (MW > 2 106 g/mol) has been used for orthopedic implant fabrications, especially for load-bearing applications such as an acetabular cup of total hip and the tibial plateau and patellar surfaces of knee joints. Biocompatability tests for PE are given by ASTM standards in F981, F639, and F755.

7. Polypropylene (PP) PP can be polymerized by a Ziegler-Natta stereospecific catalyst which controls the isotactic position of the methyl group. Thermal (Tg:-12C, Tm:125~167C and density: 0.85~0.98 g/cm3) and physical properties of PP are similar to PE. The average molecular weight of commercial PP ranges from 2.2~7.0 105 g/mol and has a wide molecular weight distribution (polydispersity) which is from 2.6 to 12. Additives for PP such as antioxidants, light stabilizer, nucleating agents, lubricants, mold release agents, antiblock, and slip agents are formulated to improve the physical properties and processability. PP has an exceptionally high flex life and excellent environment stress-cracking resistance, hence it had been tried for finger joint prostheses with an integrally molded hinge design [Park, 1984]. The gas and
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water vapor permeability of PP are in-between those of LDPE and HDPE. PP is used to make disposable hypothermic syringes, blood oxygenator membrane, packaging for devices, solutions, and drugs, suture, artificial vascular grafts, nonwoven fabrics, etc. 8. Polymethylmetacrylate (PMMA) Commercial PMMA is an amorphous (Tg:105C and density:1.15~1.195 g/cm3) material with good resistance to dilute alkalis and other inorganic solutions. PMMA is best known for its exceptional light transparency (92% transmission), high refractive index (1.49), good weathering properties, and as one of the most biocompatible polymers. PMMA can be easily machined with conventional tools, molded, surface coated, and plasma etched with glow or corona discharge. PMMA is used broadly in medical applications such as a blood pump and reservoir, an IV system, membranes for blood dialyzer, and in in vitro diagnostics. It is also found in contact lenses due to excellent optical properties, dentures, and maxillofacial prostheses due to good physical and coloring properties, and bone cement for joint prostheses fixation (ASTM standard F451). Another acrylic polymer such as polymethylacrylate (PMA), polyhydroxyethylmethacrylate (PHEMA), and polyacrylamide (PAAm) are also used in medical applications. PHEMA and PAAm are hydrogels, lightly cross-linked by ethyleneglycoldimethylacrylate (EGDM) to increase their mechanical strength. The extended wear soft contact lenses are synthesized from PMMA and Nvinylpyrollidone or PHEMA which have high water content (above 70%) and a high oxygen permeability. 9. Polystyrene (PS) and its Co-Polymers PS is polymerized by free radical polymerization and is usually atactic. Three grades are available; unmodified general purpose PS (GPPS, Tg:100C), high impact PS (HIPS), and PS foam. GPPS has good transparency, lack of color, ease of fabrication, thermal stability, low specific gravity (1.04~1.12 g/cm3), and relatively high modulus. HIPS contains a rubbery modifier which forms chemical bonding with the growing PS chains. Hence the ductility and impact strength are increased and the resistance to environmental stress-cracking is also improved. PS is mainly processed by injection molding at 180~250C. To improve processability additives such as stabilizers, lubricants, and mold releasing agents are formulated.
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GPPS is commonly used in tissue culture flasks, roller bottles, vacuum canisters, and filterware. Acrylonitrile-butadiene-styrene (ABS) copolymers are produced by three monomers; acrylonitrile, butadiene, and styrene. The desired physical and chemical properties of ABS polymers with a wide range of functional characteristics can be controlled by changing the ratio of these monomers. They are resistant to the common inorganic solutions, have good surface properties, and dimensional stability. ABS is used for IV sets, clamps, blood dialyzers, diagnostic test kits, and so on. 10. Polyesters Polyesters such as polyethyleneterephthalate (PET) are frequently found in medical applications due to their unique chemical and physical properties. PET is so far the most important of this group of polymers in terms of biomedical applications such as artificial vascular graft, sutures, and meshes. It is highly crystalline with a high melting temperature (Tm: 265C), hydrophobic and resistant to hydrolysis in dilute acids. In addition, PET can be converted by conventional techniques into molded articles such as luer filters, check valves, and catheter housings. Polycaprolactone is crystalline and has a low melting temperature (Tm: 64C). Its use as a soft matrix or coating for conventional polyester fibers was proposed by recent investigation. 11. Polyurethanes Polyurethanes are usually thermosetting polymers: they are widely used to coat implants. Polyurethane rubbers are produced by reacting a prepared prepolymer chain with an aromatic di-isocyanate to make very long chains possessing active isocyanate groups for cross-linking. The polyurethane rubber is quite strong and has good resistance to oil and chemicals. 12. Polyacetal, Polysulfone, and Polycarbonate These polymers have excellent mechanical, thermal, and chemical properties due to their stiffened main backbone chains. Polyacetals and polysulfones are being tested as implant materials, while polycarbonates have found their applications in the heart/lung assist devices, food packaging, etc. Polyacetals are
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produced by reacting formaldehyde. These are also sometimes called polyoxymethylene (POM) and known widely as Delrin (DuPont). These polymers have a reasonably high molecular weight (>2 104 g/mol) and have excellent mechanical properties. More importantly, they display an excellent resistance to most chemicals and to water over wide temperature ranges. Polysulfones were developed by Union Carbide in the 1960s. These polymers have a high thermal stability due to the bulky side groups (therefore, they are amorphous) and rigid main backbone chains. They are also highly stable to most chemicals but are not so stable in the presence of polar organic solvents such as ketones and chlorinated hydrocarbons. Polycarbonates are tough, amorphous, and transparent polymers made by reacting bisphenol A and diphenyl carbonate. It is noted for its excellent mechanical and thermal properties (high Tg:150C), hydrophobicity, and antioxidative properties. Viscoelastic Behavior of Polymers Viscoelasticity is the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation. Elastic materials strain instantaneously when stretched and just as quickly return to their original state once the stress is removed. Viscoelastic materials have elements of both of these properties and, as such, exhibit time dependent strain. Whereas elasticity is usually the result of bond stretching along crystallographic planes in an ordered solid, viscoelasticity is the result of the diffusion of atoms or molecules inside of an amorphous material. All materials exhibit some viscoelastic response. Synthetic polymers, wood, and human tissue as well as metals at high temperature display significant viscoelastic effects. In some applications, even a small viscoelastic response can be significant. To be complete, an analysis or design involving such materials must incorporate their viscoelastic behavior. The behavior of complex fluids, such as polymer blends and multiblock copolymers (e.g., Estane) is intermediate between that of solids and fluids. For short times, the response is elastic and the stress is proportional to the applied strain. The effect of viscoelasticity on polymer morphology becomes even more important as the dynamical asymmetry between the polymer components increases. The behavior of the slow and fast components leads to deformation and phase separation properties that are quite unlike those observed for symmetric systems.
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The two-fluid model, in which separate velocities are needed for the monomeric components to describe viscous drag effects and the viscoelastic nature of the polymeric chains, has been reasonably successful in understanding blends and homopolymers. Many of the mesoscale properties of the system relax on timescales shorter than thermodynamic timescales and are effectively in local equilibrium on hydrodynamic timescales, which allows us to employ SCFT techniques to calculate their properties. The following demonstration illustrates the logarithmic nature of creep

Creep and recovery. Stress and strain vs. time t

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Fig.2 Regions of creep behavior. Strain vs time t, for different load levels. Creep curves may exhibit three regions, primary creep in which the curve is concave down, secondary creep in which deformation is proportional to time, and tertiary creep in which deformation accelerates until creep rupture occurs. Tertiary creep is always a manifestation of nonlinear viscoelasticity, and secondary creep is usually nonlinear as well. Although secondary creep is represented by a straight line in a plot of strain vs. time, that straight line has nothing whatever to do with linear viscoelasticity. Linear response involves a linear relationship between cause and effect: stress and strain at a given time in the case of creep. Stress relaxation is the gradual decrease of stress when the material is held at constant strain. If we suppose the strain history to be a step function beginning at time zero: (t) = 0H(t),

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The stress (t) in a viscoelastic material will decrease as shown in Figure.3. The ratio is E(t) = ( (t) / 0) is called the relaxation modulus. In linear materials, it is independent of strain level, so E(t) is a function of time alone. Stress relaxation describes how polymers relieve stress under constant strain. Because they are viscoelastic, polymers behave in a nonlinear, non-Hookean fashion.[1] This nonlinearity is described by both stress relaxation and a phenomenon known as creep, which describes how polymers strain under constant stress. Polymeric Biomaterials Applications Wound management (synthetic suture material) Clips Adhesives Surgical meshes Orthopedic devices Ophthalmic (intraocular lens) Pins (spilli) Rods (barre) Screws (viti) Tacks (chiodini) Ligaments Tissue engineering Dental applications Guided tissue regeneration Membrane Void filler following tooth extraction Cardiovascular applications (coronary arteries and the vessels) Stents Intestinal applications
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Anastomosis rings Drug delivery system Covering of permanent Implants Advantages Good biocompatibility. Possibility of changing in composition and in physical-mechanical properties. Low coefficients of friction. Easy processing and workability. Ability to change surface chemically and physically. Ability to immobilize cells or biomolecules within them or on the surface (Drug Eluting Stent). Good biocompatibility. Possibility of changing in composition and in physical-mechanical properties. Low coefficients of friction Easy processing and workability Ability to change surface chemically and physically Ability to immobilize cells or biomolecules within them or on the surface (Drug Eluting Stent) Disadvantages Presence of substances that may be issued in the body [ monomers (toxic), catalysts, additives ] after degradation. Ease of water and biomolecules absorption from surrounding. Low mechanical properties. In some cases, difficult sterilization. Polymers advantage over Metals Considerations in the selection strength.

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Overall time and rate of degradation/corrosion (a very high degradation rate can be associated with inflammations). Biocompatibility. Lack of toxicity.

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