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					\at\Medical Polymers


                 \bla\Jennifer Hoffman, Ph.D., Tao Xu, Ph.D., Suresh Donthu, Ph.D. P.E.


                                                Exponent, Inc.


Polymers offer a wide range of choices for medical applications because of their versatility in properties

and processing. Polymers offer significant advantages over metals, including resistance to degradation in

contact with physiological fluids, manufacturability/ ease of forming complex shapes and different form

factors, the ability to tailor mechanical and physical properties to mimic tissue, and the ability to

incorporate drugs for controlled drug delivery. Non-polymeric materials such as metals and glass

preceded polymers for use in medical-device applications. However, throughout recorded human history

and in various civilizations, there exist numerous references to the use of natural polymers for biological

applications, including gutta percha, natural latex, etc. The turn of the 20th century witnessed the birth of

the field of synthetic plastics and their use in medical applications, including contact lenses, ocular

implants, dental implants, artificial kidneys, and heart valves.


The early stages of synthetic plastics for medical applications were dominated by surgeon-visionary-

entrepreneurs (sometimes called “surgeon heroes”) who were eager to experiment with these materials

with the hope of providing even an incremental relief to their patients. Without even the rudimentary

understanding of contemporary biomaterial toxicology, several of these early experiments with synthetic

plastics for medical applications led to failures and such failures hindered the development of polymeric

biomaterials. However, the rapid developments made in science and engineering of plastics in the second

half of the 20th century paved the way for their acceptance in medical applications.


Currently, there are many types and grades of polymers that have a history of successful use in medical

applications. Over the last 80 years, polymers have been used in numerous types of implantable and

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peripheral devices for variety of medical applications such as those addressing neurological,

cardiovascular, ophthalmic, and reconstructive pathologies. They have also been found useful in

temporary therapies such as hemodialysis, coronary angioplasty, blood oxygenation, electrosurgery, and

wound treatment.


The choices associated with polymer selection offer an opportunity as well as pose a challenge for

researchers and developers in this field. A thorough understanding of the fundamentals of polymer

composition-structure-property relationships together with an appreciation for the nuances specific to

medical device product development form an important foundation for success as a developer and

researcher in this field.


The following sections provide a general overview of polymeric materials and the characteristics that

make them a unique class of materials, common medical plastics, regulatory aspects of material selection,

and current and future trends in medical polymers.


\a\Composition, Structure, and Properties of Polymers


Medical plastics are principally composed of a base resin and additives to create a useful portfolio of

properties. The resin may be one or more polymers, while the additives include processing aids,

antioxidants, fillers, reinforcing fibers, pigments, plasticizers, and impact modifiers that are blended with

the base polymer to prolong the life of the material and improve its physical, chemical, and aesthetic

properties. The properties of common synthetic medical polymers vary widely, and are governed by their

chemical composition, molecular weight, molecular architecture, and morphology. More detailed

information on polymer chemistry, processing, and properties can be found in the References section at

the conclusion of this chapter.




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\b\Chemical Composition of the Polymer Backbone


Polymers are comprised of long chain-like molecules with repeat units of atoms known as monomers

(polymer = many mers). The atoms within a molecule are held together by strong covalent bonds. The

most common atoms in organic polymers are carbon, hydrogen, oxygen, and nitrogen, while silicones,

based on silicon and oxygen atoms, are an important family of inorganic polymers. Functional groups

attached to the backbone also determine critical characteristics of the polymer.


The chemical composition of a given polymer describes the arrangement (configuration) of atoms along

the backbone. Polymers that have a single repeat unit or a monomer are called homopolymers, while

those with two or more types of monomers are called copolymers. For example, polyethylene consists of

a single type of repeat unit, and is an example of a homopolymer, while ABS (acrylonitrile butadiene

styrene) is a copolymer of three types of monomers: styrene, acrylonitrile, and butadiene. The properties

of copolymers depend on the sequence of monomer units in the backbone (e.g., statistical, random, or

alternating). Common medical copolymers include thermoplastic elastomers such as thermoplastic

polyurethane (TPU) and polyether-block-amide (PEBA).


The chemical nature of the monomers in a polymer will affect its interaction within the molecule and with

neighboring molecules. For example, block copolymers will order and ultimately behave differently than

random copolymers. Likewise, when two or more polymers are mixed to create a blend, intermolecular

interactions determine miscibility. If the polymers interact strongly, they will be miscible and create a

single phase with blended properties, while less favorable interactions can create a two-phase morphology

with different attributes.


\b\Molecular Weight


Polymeric materials contain a large number of individual chains with varying lengths and mass, and

therefore a range of molecular weights that cannot be fully described by a single number. In general, as
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molecular weight increases, the mechanical property performance such as resistance to creep and stress

relaxation increases because longer molecules tend to have more entanglements with neighboring

molecules and it is more difficult for chains to move and slide past each other (see Fig. 1). However,

above a critical molecular weight for a given polymer, the melt viscosity increases exponentially with

marginal improvements in properties creating difficulties during melt processing such as injection

molding (see Error! Reference source not found.Fig. 2). Thus, a balance of high and low molecular

weights is needed to obtain good physical properties and permit reasonable processing conditions.


Intrinsic viscosity and melt flow index are fairly quick and inexpensive methods that provide indirect

measurements of average molecular weight of thermoplastic materials and can be used for quality control

purposes and troubleshooting part failures. Intrinsic viscosity is measured from the flow time of a solution

through a capillary. Melt flow index is a measure of the ease of flow of the melt of a thermoplastic

polymer. It is defined as the mass of polymer, in grams, flowing in ten minutes through a capillary of a

specific diameter and length under a specified pressure. The melt flow index is a point measurement

associated with specific testing conditions and is often provided on technical data sheets as a guide to

processability. It can be a useful comparator between lots, or within a specific polymer family.


The molecular weight distribution of thermoplastics can be more fully evaluated using gel permeation

chromatography (GPC). The molecular weight is described in terms of statistical averages: Mn = number

average, Mw = weight average and Mz = z-average. A typical molecular distribution plot is shown in

Error! Reference source not found.Fig. 3 and is characterized by polydispersity index (PDI), which is

the ratio of the weight average and number average molecular weights (Mw/Mn), and is an indicator of the

breadth of the molecular weight distribution. Physical properties often track with Mw, and melt processing

via extrusion generally correlates most closely with Mz.




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\b\Molecular Architecture


Polymer molecules can be linear, branched, or crosslinked into a three-dimensional network. In the bulk,

polymers can be either amorphous or semi-crystalline. Amorphous polymers tend to have irregularity in

their chain structure and often contain large side groups, which prevents the chains from forming ordered

structures or crystalline zones. On the other hand, crystalline polymers are more regular and ordered than

amorphous polymers, but are truly only semi-crystalline (partly crystalline, partly amorphous) as a

consequence of their long-chain nature and subsequent entanglements. Linear semi-crystalline polymers

(e.g. high density polyethylene) typically have higher levels of crystallinity than branched polymers (e.g.

low density polyethylene); branches make it difficult for polymer chains to pack closely together and

form crystals.


Amorphous polymers are characterized by a major thermal transition called the glass transition. The glass

transition temperature (Tg) is generally defined as the temperature above which polymers show segmental

chain motion. As a result, going through Tg results in dramatic changes in properties such as permeability,

creep resistance and stiffness. At temperatures below Tg, amorphous polymers tend to be glassy, hard and

brittle, while above Tg, they tend to be rubbery.


In contrast to amorphous polymers, semi-crystalline polymers exhibit two major thermal transitions, the

glass transition and melting, which is defined by the melting temperature (Tm). During melt processing of

thermoplastics, amorphous polymers must be heated above Tg and semi-crystalline polymers above Tm.

Semi-crystalline polymers tend to exhibit greater shrinkage from the melt due to crystallization. In

structural (load-bearing) applications, amorphous polymers must be used at temperatures below Tg while,

semi-crystalline polymers are structurally useful below Tm.




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\b\Morphology


Morphology describes form and structure and polymer morphology is related to the distribution and

association of structural units. A polymeric material contains thousands or millions of molecules that

entangle with each other and interact through secondary bonding (e.g., weak van der Waals forces or

hydrogen bonding). Morphology develops as a result of structural aspects of a polymer, such as crystal

size and distribution in semi-crystalline polymers, molecular orientation from melt-processing,

size/shape/distribution of fillers/reinforcements, and the degree of phase separation for copolymers. For

example, extruded polymers tend to have a high degree of molecular orientation and a higher

strength/stiffness in the extrusion direction.


Copolymers offer excellent examples of the importance of morphology: they can behave like rubber-

toughened glassy materials at one extreme or glass-reinforced rubber materials at the other. For example,

ABS typically behaves as a rubber-toughened glassy material. As shown in Error! Reference source not

found.Fig. 4, the rigid SAN phase is the continuous phase while the grafted butadiene rubber segregates

into domains that are dispersed throughout. The rubber imparts toughness to an inherently rigid material.


\b\Viscoelasticity


Physical properties of polymers are the result of their long chain nature, the interactions due to backbone

chemistry, and the morphology that develops from molecular architecture and ordering. Due to their

molecular nature, polymers exhibit both liquid- and solid-like characteristics. Similar to liquids, polymers

deform slowly with time under stress (i.e. creep). Polymers also store some elastic energy when subjected

to stress and may recover a portion of their deformation when stress is removed (elastic recoil). This

hybrid nature is often modeled as combinations of dashpot (viscous) and spring (elastic) elements.


Polymer properties are time and temperature dependent, as illustrated in Error! Reference source not

found.Fig. 5. In general, at high strain rates (e.g. impact loading) and low temperatures, polymers
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respond more like elastic solids. Conversely, at low strain rates and high temperatures, polymers behave

more like viscous fluids as the polymer chains can disentangle and slide past each other.


\a\Classification of Polymers


There are many ways to classify polymers, including the polymerization method (how it was made), how

the material deforms, or molecular origin or stability.


\b\Polymerization


Classification by polymerization is useful because polymers made by condensation or addition tend to

have differing polydispersity, maximum molecular weight, and environmental stability. Addition

polymers such as polyolefins and polyacrylates grow by sequential addition of monomers to growing

chains. By controlling the initiation sequence, polymers of high average molecular weight and narrow

molecular weight distribution can be synthesized. The monomers have essentially the same molecular

formula as the resulting repeat unit. When they decompose, the mechanism is typically random scission

or unzipping of the molecule.


In contrast, condensation polymers grow by combining two monomers to create a repeat unit with a

different molecular formula than those of the monomers from which it was produced. For example,

polyester polymers are formed by the reaction of acids and alcohols, with water as a byproduct. Average

molecular weight builds slowly, with a polydispersity index close to 2. Condensation polymers are

subject to degradation when conditions favor the reverse of the polymerization reaction (e.g. when water

is present at high temperatures, the equilibrium favors re-generation of monomers).


\b\Thermomechanical Response


Polymers are most commonly classified into three groups: thermoplastics, thermosets, and elastomers

(rubbers), which are terms related to how the materials deform. The group most widely used for medical
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applications is thermoplastics. Thermoplastics are linear or branched polymers that flow upon the

application of heat; they can be molded and remolded using conventional melt processing methods,

including thermoforming, extrusion, and injection molding.


Thermosets (thermosetting polymers) are cross-linked polymers that are rigid and intractable (insoluble).

They consist of a three-dimensional molecular network where the molecules are connected together by

chemical links (covalent bonds). Thermosets form a permanent and infusible shape after the application

of heat or a curing agent; they cannot be remelted and reformed once shaped and cured. Epoxy adhesives

and silicone materials are examples of thermosets. These materials start off as liquid-like or semi-solid

materials and an irreversible chemical reaction occurs that causes the material to harden (cure or

crosslink).


Rubber materials are thermosets that exhibit elastomeric properties (i.e. they can be stretched easily and

will spring back when the stress is released). Rubber materials are relatively soft and deformable at

ambient temperatures. Their primary uses are for seals, adhesives, and molded flexible parts. Silicone is

an example of a common thermoset rubber material.


A thermoplastic elastomer (TPE) is a thermoplastic material that can have rubber-like properties. TPEs

are typically block copolymers that are comprised of hard and soft segments (blocks) that are phase

separated in the solid state. The hard blocks impart stiffness and strength and the soft blocks impart

flexibility. By varying the length and ratio of the hard and soft blocks, a wide range of properties can be

achieved. Unlike thermosets, TPEs have physical crosslinks, which are relatively weak intermolecular

bonds within and between blocks. These bonds break upon heating and reform upon cooling.




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\b\Material Source and Stability


Another way that polymers can be classified is based on the source of the monomers, or the polymers

themselves. Natural polymers with applications in the medical arena include DNA, polysaccharides,

proteins, silk, cellulose, etc. Most medical polymers are synthetic.


Some natural and synthetic polymers are biodegradable (i.e., bioresorbable or bioabsorbable) and

inherently degrade in physiological conditions, typically as the result of the presence of moisture (i.e.

hydrolysis). The products from hydrolysis are further broken down and eliminated through normal

metabolism. The rate of degradation can be tailored with chemical composition and molecular

architecture.


\a\Common Medical Polymers


A majority of medical polymers are synthetic polymers, with properties that vary widely based on the

attributes described above, including crystallinity (see Error! Reference source not found.Table 1).

Common medical thermoplastics are listed in Error! Reference source not found.Table 2 and Error!

Reference source not found.Table 3.


Amorphous polymers are generally transparent while semi-crystalline polymers are usually translucent or

opaque. Crystals tend to scatter light, particularly if their size or the distance between crystals is on the

order of the wavelength of visible light. Thus, amorphous polymers are desirable for applications such as

containers, syringes, and blood bags, which require transparency. Generally, semi-crystalline polymers

tend to have better chemical resistance than amorphous polymers. However, modified acrylics have

demonstrated fat and lipid resistance, which are important for applications such as disposable intravenous

luer locks and filter housing components.




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Engineering and high performance thermoplastics such as PSU (polysulfone), PC (polycarbonate), and

PEEK (polyether ether ketone), possess aromatic ring structures in their backbone, which lends to higher

glass transition temperatures, enhanced mechanical properties, and greater heat and chemical resistance

compared to commodity thermoplastics such as ABS, PE (polyethylene), PS (polystyrene), and PMMA

(poly(methyl methacrylate)). The engineering and high performance thermoplastics are typically used for

surgical tools and implantable devices, while the commodity thermoplastics are more often used for

disposables.


PE is one of the most common commodity plastics used in medical-device applications. There are several

types of PE that have different chain architecture and molecular weight, which affect their physical

properties (see Error! Reference source not found.Table 4). Low density polyethylene (LDPE) and

linear low density polyethylene (LLDPE) have branched side chains and a relatively low molecular

weight, providing the processability and tear and puncture resistance required for bags, containers, and

disposable packaging. Ultra high molecular weight polyethylene (UHMWPE) has extremely high

molecular weight with significant molecular entanglements, providing enhanced wear resistance for use

in joint prostheses.


\a\Materials Selection


When approaching the task of materials selection, polymers can be classified into three main groups as

mentioned in the Classification of Polymers section. Each group of polymers has unique properties,

which can be used as criteria for pre-screening. It is important to recognize that polymers exhibit time

(frequency) and temperature dependent properties, as noted in the Viscoelasticity section, including non-

linear stress and strain behavior. Other unique features that set polymers apart from metals and ceramics

include: aging and weathering, chemical resistance, environmental stress cracking, notch sensitivity,

residual stresses and weld lines from processing, process-driven morphology, and the effects of additives,

fillers, and reinforcements.
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Establishing relevant criteria can help guide the selection process. Ashby’s material selection strategy is

described by the following four steps1: \bl\


          Translate design requirements: Express as function, constraints, objectives, and free variables

          Screen using constraints: Eliminate materials that cannot do the job

          Rank using objective: Find the screened materials that do the job best

          Seek supporting information: Research the family history of top-ranked candidates


Medical polymer selection criteria will be application dependent, but may include the following: \bl\


          General

                o    Aesthetics, cost

          Mechanical

                o    Elastic moduli (Young’s, shear, bulk), elongation at break, yield strength, ultimate

                     strength, compressive strength, impact resistance, hardness, fatigue endurance, stress

                     relaxation, creep

          Thermal

                o    Glass transition temperature, melting temperature, maximum/minimum continuous

                     service temperature, thermal conductivity, specific heat, thermal expansion coefficient

          Environmental

                o    Chemical resistance, UV resistance, thermo-oxidative stability, environmental stress

                     cracking resistance



1
    Ashby, M. F., Materials selection in mechanical design, 3rd ed., Elsevier, 2005.

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       Compatibility

            o    Biocompatibility, USP classification, compatibility with other materials in the device, the

                 manufacturing process, and sterilization and use conditions

       Others

            o    Optical, electrical


The information on product data sheets is most useful for screening materials and should not, alone, be

used for purposes of design. Data sheets typically provide single point data (at ambient temperature) from

short-term tests, rarely considering the effects of time and environmental conditions (temperature,

humidity, and chemicals) on material properties. For design purposes, it is important to evaluate material

properties at the end-use temperature (e.g. 37°C (98.6°F) for implantable applications) and under

anticipated loading conditions. For example, if a polymeric medical component will be subjected to cyclic

loading, then fatigue testing should be performed at the same frequency and loads. Modeling and

simulation (e.g., finite element analysis or FEA) can also be a useful tool for assessing product

performance based on material behavior at relevant temperatures, rates, or service histories.


\b\Regulatory Aspects of Materials Selection


Historically, plastics for medical applications have been grouped into six classes according to the

guidelines developed by United States Pharmacopeia (USP), a non-governmental standard setting

organization. In 1960, USP established the test methodology and performance requirements for plastic

materials to be used in medical applications. The USP tests measure the biological reactivity of plastics in

contact with mammalian cell cultures and via implantation of the plastics and injection of the plastic

extractables into laboratory animals. The six USP classes are defined based on responses to three in-vivo

tests for which extracts, materials, and routes of administration are specified. The three in-vivo tests are

acute systemic toxicity test, irritation test, and implantation test. Error! Reference source not
                                                                                                               12
found.Table 5 lists the in-vivo tests that a medical plastic needs to pass in order to receive one of the six

classifications. For example, an USP class VI plastic would have passed the acute systemic toxicity test

and irritation test when strips of the plastic are implanted into the animal.


Though USP guidelines are adopted by most of the medical-device manufacturers, especially during the

initial materials selection stage, these guidelines are meant for medical plastics alone and not for the

plastics as part of a medical device. Whenever a plastic is used in a medical device, even if it is advertised

as a USP class VI material, it should be tested according to the standards relevant to the amount of contact

with the human anatomy as an integral part of the device. This is because factors such as the addition of

colorants, processing, and the use of the plastic in combination with other materials and adhesives, can

affect the biocompatibility characteristics of the material. Furthermore, as part of the device, the plastic

may have been subjected to processing conditions unique to the application such as texturing, surface

treatment, fabrication process, etc. that could potentially alter the biocompatibility response of a particular

medical plastic. For these reasons, the device level tests should be performed, even if the same material is

in use in another medical device. However, using a material that is already in use in another medical

device for similar function that is known to have passed biocompatibility testing can instill some

confidence that the material will pass testing in new application. Therefore, a designer should only use

USP classification of plastics as a guide during initial materials selection screening process.


\a\Failure Analysis and Prevention


Despite the best efforts of designers, failures can and do happen during the development, clinical (in the

case of medical-device manufacturers), pre-market, or post-market stages. Failure may be defined as a

loss or unacceptable change in the fit, form, or function of a given component or structure. As much as

possible, failure modes are anticipated during the development process and considered in the design,

testing, and labeling of the product. When failures do occur, the failure analysis process allows

investigators to determine the root cause of failures that arise at different stages of the product life cycle.
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Failure investigations are performed to gather the necessary scientific and engineering information to

make informed decisions and identify the best solution to a given problem. Knowledge gained from

failure analysis enables prevention of future occurrences, and/or improvement of the performance of the

component or device. Thus, failure analysis plays an important role in product development and design

improvement, liability assessment, and planning and executing potential recall or replacement campaigns.


\b\The Failure Analysis Process


At any stage of a medical-device life cycle, the engineering and scientific investigation process used to

determine the root cause is fundamentally similar. Specifically for post-market device failures,

manufacturers should process and analyze failed devices per the Code of Federal Regulations (21CFR

Part 820). An important step in any failure investigation is accurately and clearly defining the problem

statement such that the true root-cause can be identified and proper corrective actions are implemented.

The failure investigation and analysis help determine the actual failure mechanism and Section 820.100

provides guidelines for performing corrective or preventive actions.


The failure analysis process entails information mining (fact collection), non-destructive examination

(NDE), and possible destructive testing. When sufficient information is available, numerical modeling

(such as finite-element analysis) can also be an effective tool for identifying and correcting the root cause

of a failure. One advantage of this approach over experimental analysis is the ability to explicitly include

more conditions than would be possible due to practical limitations associated with available materials,

devices, or time. In addition, sensitivity analyses and analysis iterations can be performed quickly with a

numerical model. Modeling can also provide an effective communication tool with regulatory bodies

since it allows the user to create to both cross-sectional and overall images of devices throughout an

analysis.




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NDE includes visual and/ or microscopic examination. Visual examination allows for examination of

macroscopic features, including tell-tale signs such as discoloration and deformation, and to obtain

dimensional measurements. Microscopic examination may be necessary to examine certain features at

higher magnification, and to gain a deeper understanding of the failure mode. If the analysis is limited to

NDE methods, the examination should be carefully planned before commencing the work, in order to

negate the possibility of damaging the samples. An Environmental Scanning Electron Microscope

(ESEM) is a common tool used for NDE of polymeric medical device parts because it does not require

coating the sample with a conductive material prior to imaging. However, some level of vacuum is still

generated, which may make the tool inappropriate for devices that may offgas or deform under these

conditions.


Other common tools used to investigate failures that are typically destructive include chemical, physical,

and mechanical property evaluation. Fourier-transform infrared spectroscopy (FTIR) is a workhorse tool

that can be used non-destructively or destructively to quickly ascertain the composition of polymeric

materials and look for evidence of contamination and degradation. If there are trace contaminants or small

amounts of degradation, other more sensitive methods such as various forms of chromatography and

spectroscopy can be used. Thermal analysis techniques such as differential scanning calorimetry (DSC),

thermogravimetric analysis (TGA), thermomechanical analysis (TMA), and dynamic mechanical analysis

(DMA) can be used to confirm that the material used met the specification for composition and exhibit

similar critical attributes. Molecular weight analysis can also be used to confirm conformance with

specifications, and it can be used as a tool to evaluate for evidence of molecular degradation in

thermoplastic materials.


Destructive testing is most effective when it includes comparative analyses with parts or devices from

manufacturing lots that have not exhibited failures. For example, an injection molded part in a medical

device may have cracked post-sterilization. The failure analyst should evaluate sterilized and non-

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sterilized parts, as well as cracked and non-cracked parts from devices that have been sterilized for

evidence of material degradation.


\b\Plastic Product Failure Analysis


Product failures can occur for many reasons, including deficient design, use of improper materials for the

application, defective materials, mistakes in manufacturing, abuse during end-use or use in an unintended

manner. Failure analysis of plastic parts should include recognition of the chemical, thermal, and physical

responses that are unique to polymers.


Failure mechanisms in polymers can be physical or chemical in nature. Each type of polymer has inherent

weaknesses, which are a function of its composition and the application environment (temperature, stress,

strain, duration, chemical exposure). Error! Reference source not found.Table 6 lists mechanisms of

physical and chemical deterioration that may occur alone or in concert at various stages of a polymer

history, from processing and assembly to storage and end-use. Moreover, the treatment of a material prior

to use may predispose it to stable or unstable end-use behavior. A prominent example of biomaterial

degradation caused by pre-implant processing is gamma irradiation sterilization of UHMWPE used in

total joint prostheses. The process generates free radicals within the material that react with oxygen to

produce undesirable oxidation products. Oxidation and chain scission can occur for periods of months to

years, causing loss of strength and embrittlement, with limited shelf life.


\c\Design.\ce\ When developing new products, engineers must consider the geometry (dimensions and

tolerances) and the materials of construction. The geometry must be appropriate for the material (e.g. ease

of processability) and the material must be appropriate for the application (e.g. sterilizable by available

methods, biocompatible, possess critical physical and mechanical properties, etc.). A designer may have

chosen a great material that has all of the desired attributes required for a given application, but if the



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geometry is such that it exposes a weakness in the material, the component/device may fail due to an

inherent design defect.


For example, some thermoplastics are more notch sensitive than others, which means that properties such

as impact strength are strongly dependent on notch radius. For notch sensitive materials such as rigid

PVC, the impact strength drops precipitously with decreasing radius. This is shown in Error! Reference

source not found.Fig. 6, which also illustrates that acrylic and ABS are not as notch sensitive as rigid

PVC, and that notch size can affect the relative impact strength of rigid PVC compared to ABS. Therefore,

generous inside corner radii are recommended to minimize stress concentrations and the potential for

corner cracking, especially with notch-sensitive materials.


\c\Aging and Environmental Effects.\ce\ Medical-device designers must also consider shelf life/aging of

the material to ensure that the material retains acceptable performance over its lifetime in the intended use

environment. Unlike metals and ceramics, plastics are particularly susceptible to degradation from aging,

which results from exposure to UV radiation and is accelerated at higher temperatures and in the presence

of moisture. Typically, this leads to discoloration, loss of mechanical properties, or in extreme cases,

disintegration of the plastic product.


\d\Shelf-Life Aging Study- Case Study.\de\ Accelerated aging tests were performed on two polyether-

block-amide (PEBA) copolymer tubing samples to evaluate the best sterilization method for extending

shelf life. Samples were constructed with a 63D PEBA inner tube covered by a stainless steel coil and

over-coated with extruded 25D or 40D PEBA outer tubing. The mechanical properties and hardness of

PEBA materials are dependent on the ratio of ether soft blocks to amide hard blocks; hardness is reduced

and flexibility is increased with increasing polyether content. Thus, tubing made with 25D PEBA is more

flexible than tubing made with 40D PEBA.




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Samples were sterilized using gamma or e-beam radiation followed by accelerated aging between 40 and

80°C (100 to 180°F). Assuming Arrhenius behavior for a first approximation, the failure times for e-beam

sterilized samples, regardless of PEBA hardness, were longer. In addition, gamma sterilized 40D samples

had longer failure times than the lower hardness 25D sample. Materials characterization was performed

before and after sterilization and after aging to evaluate compositional changes. Based on FTIR analysis,

it was determined that the polyether blocks were degrading during aging. Thus, the higher hardness 40D

sample was more stable as a result of its decreased polyether block content. In addition, the estimated

shelf life of 25D tubing samples is greatly increased when sterilized with e-beam radiation compared to

gamma radiation. This study helped a medical device manufacturer select an appropriate sterilization

method for their devices.


\c\Processing.\ce\ Plastic components used in medical devices are often made using molding and

extrusion processes, during which the plastic part is shaped by application of heat and pressure. These

high-energy processes can result in residual stresses and latent defects due to improper processing

conditions, and contamination during processing. Defects could also be introduced during casting, curing,

and secondary processes such as assembly, packaging, and sterilization, which can result in subsequent

product failures.


\d\Polyurethane Medical Device Component – Case Study.\de\ A polyurethane medical device developed

a through-wall crack during pre-clinical testing. Nondestructive visual examination revealed cracks on the

exterior surface. Destructive examination was subsequently performed to characterize the nature and

extent of the damage. Based on microscopic examination of the fracture surface, it was determined that

the crack initiated on the exterior surface at an inclusion/defect with similar elemental composition as the

device material (Error! Reference source not found.Fig. 7).


The device component was manufactured by dip coating a mandrel in a vessel containing a polyurethane

dispersion. The inclusion was most likely a hardened piece of polyurethane that sloughed from the side
                                                                                                          18
walls of the vessel and got embedded in the device cross-section during successive dips into the

dispersion. This inclusion acted as a stress concentrator. The root-cause of failure was contamination

during processing.


\d\Medical Balloons- Case Study.\de\ Medical balloons are used for a variety of medical procedures

including angioplasty and stent delivery. Non-compliant nylon balloons were rejected during

manufacturing due to the presence of various defects, including burnt polymer (e.g. ‘black specks’) and

fibrous and particulate contamination. The defects were characterized using a combination of microscopy

and spectroscopy methods to identify the location (surface or subsurface) and type of material (inorganic

or organic) within the balloon wall. Due to the transparency and glossiness of the balloons, scanning

electron microscopy (SEM) was more useful than optical microscopy for examining surface features.

Energy dispersive X-ray spectroscopy (EDS) and FTIR were used to identify inorganic elements and

organic materials, respectively. Based on SEM examination of the balloon surfaces, elliptical-shaped

features were detected on the interior surface.


The major axis of the features was essentially parallel to the extrusion direction of the tubing used to

manufacture the balloon (Error! Reference source not found.Fig. 8). The defects had metallic particles

partially embedded in the surface at symmetric positions about the major axis. These particles were likely

introduced during extrusion, possibly from worn barrel or die surfaces. When the balloon shape was

created by blow molding to radially expand the tubing, the elliptical shaped damage zone was created

around the embedded particles. After the root cause was identified, the manufacturer instituted frequent

purging of the extrusion lines and replacement of screen packs to mitigate the contamination problem.


\a\Current and Future Trends in the Use of Medical Polymers


The use of polymers in healthcare continues to expand in both disposable and non-disposable applications.

With the growth of rapidly aging populations in many developed countries and the opening of emerging

                                                                                                           19
markets, the demand for medical devices and medical polymers is anticipated to grow significantly. This

provides tremendous impetus for the development of new grades of medical polymers, and newer

applications and improvements in performance of the existing grades of materials.


\b\High-Performance Polymers for Implants


Materials used in prosthetic implant applications require high biocompatibility and mechanical properties

that are stable over a long period of time while in contact with human body fluids. Traditionally, metals

such as titanium have been used for these applications. Over the last decade, advances in high

performance implantable polymers such as PEEK, other aromatic polymers, cross-linked UHMWPE, and

composite formulations have enabled these materials to overcome some of the short-comings of

polymeric materials for orthopedic applications.


\b\Tissue Engineering


Tissue engineering can be defined as an interdisciplinary field in which the principles of engineering and

the life sciences are applied toward the generation of biological substitutes aimed at creation, preservation,

or restoration of lost organ function. The ultimate goal of tissue engineering is to either implant tissues

that have been grown on biomaterials outside the body or provide the body with appropriate biomaterial

scaffolds and biological ingredients so that it can regenerate the diseased or missing tissue.


One of the key components in the successful tissue engineering is the production of the correct scaffold

using biomaterials. The scaffold should be biocompatible, highly porous, provide the correct

biomechanical environment, degrade in tune with tissue growth and possess a surface that encourages cell

attachment and growth. The scaffold can be permanent or bioabsorbable/ bioresorbable and can be

surface functionalized to enhance biocompatibility and stimulate growth. Thus, the ideal scaffold should

provide cells not only with a structural framework but also with appropriate mechanical and biochemical

conditions so that these cells can proliferate and produce extracellular matrix to form tissue.
                                                                                                              20
\b\Bioresorbable Polymers


Bioresorbable polymers have found use in tissue scaffolds, orthopedic, and suture materials. These

materials bring benefits of tailored duration, and their properties and persistence in the body can be

tailored by chemistry and morphology. For example, properties and persistence of copolymers based on

lactic and glycolic acids are directly related to the percent, arrangement and associated crystallinity. New

bioresorbable materials such as PDO (polydioxinone) are finding use in medical devices.


\a\Summary


As in any end-use, polymer suitability is driven by structure-property-processing relationships and, with

medical devices, the addition of biocompatibility requirements. This chapter provides an overview of

these concepts and selected examples. Numerous resources (see Selected References) exist to provide a

more in-depth understanding.




                                                                                                          21
\e\References:




Polymer Chemistry, Processing, and Properties




Polymeric Biomaterials and Applications


   1. Handbook of Biomedical Plastics, Henry Lee and Kris Neville, Pasadena Technology Press, 1971.

   2. M. Moukwa, The Development of Polymer-Based Biomaterials Since the 1920s, J. of Materials,

       Feb 1997, 46-50.

   3. Medical Applications of Plastics, Biomedical Materials Symposium No.1, Ed. Harry Gregor,

       Interscience Publishers, 1971.

   4. Synthetic Biomedical Polymers-Concepts and Applications, Ed. M. Szycher, W.J.Robinson,

       Technomic Publishing Company, 1980.

   5. Polyurethanes in Medicine, Michael Lelah and Stuart Cooper, CRC Press, 1986.




                                                                                                 22
   6. A.J. Coury, Chemical and Biomechanical Degradation of Polymers, Biomaterials Science: An

       Introduction to Materials in Medicine, B.D. Ratner, A.S. Hoffman, F.J. Schoen, and J.E. Lemons,

       Ed., Academic Press, 1996.

   7. Ref 2 (original handbook)

   8. Ref 3 (original handbook)

   9. Ref 4 (original handbook)

   10. Ref 6 (original handbook)

   11. Ref 7 (original handbook)

   12. Ref 8 (original handbook)

   13. Ref 9 (original handbook)

   14. Ref 10 (original handbook)

   15. Ref 11 (original handbook)

   16. Ref 12 (original handbook)

   17. Ref 13 (original handbook)

   18. Ref 14 (original handbook)


Medical Device Design


   19. Ashby, M. F., Materials selection in mechanical design, 3rd ed., Elsevier (2005).

   20. The medical device R&D handbook, Theodore R. Kucklick, CRC press, 2006.

   21. M. Helmus et.al, Biocompatibility: Meeting a Key Foundational Requirement of Next-Generation

       Medical Devices, Toxicologic Pathology, 36, 2008, 70-80.

   22. FDA website (http://www.fda.gov/MedicalDevices/default.htm)

   23. “Design Data for Plastics Engineers,” N. Rao and K. O’Brien, Hanser Gardner Publications,

       1998.



                                                                                                   23
   24. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevi

       ce/ucm051512.htm


Failure Analysis


   25. Characterization and Failure Analysis of Plastics, ASM International, 2003.

   26. Handbook of Plastics Testing and Failure Analysis, Vishu Shah, 3rd edition, Wile-Interscience,

       2007.

   27. Kurtz, SM, The UHMWPE Handbook, Elsevier Academic Press, 2004.

   28. Hoffman, JM, Reitman, MTF, and Ledwith, P, Society of Plastics Engineers Annual Technical

       Conference, ANTEC 2008, 1777-1781.

   29. Sjong, A, Villagomez, F, and A Kendale, Society of Plastics Engineers Annual Technical

       Conference, ANTEC 2006, 1544-1548.




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