Hardcover: 504 pages
`Publisher: Prentice Hall; 1 edition
`(January 12, 2008) Language: English
`ISBN-10: 0130097101 ISBN-13:
`978-0130097101
`Product Dimensions: 10.2 x 8.4 x 0.9
`inches
`
`
`
`(cid:20)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:21)(cid:20)(cid:3)(cid:82)(cid:73)(cid:3)(cid:22)(cid:21)
`
`MILLENIUM EXHIBIT 2029
`Baxter Healthcare Corp. et al. v. Millenium Biologix, LLC
`IPR2013-00582, -00590
`
`

`

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`>US
`we
`Jrk
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`
`Materials for
`Biomedical
`Applications
`
`CH A P TE R
`
`Main Objective
`
`To understand what the field of biomaterials encompasses, to appreciate the gen(cid:173)
`eral concerns of a biomaterialist, and to review principles from general chemistry
`as needed.
`
`Specific Objectives
`
`1. To understand the breadth of the field and important consensus definitions
`relating to biomaterials.
`2. To be able to compare/contrast natural and synthetic materials.
`3. To be able to compare/contrast surface and bulk properties and understand
`that design criteria depend on the final application.
`4. To understand that the material induces a biological response which can, in
`turn, affect the material performance.
`5. To understand that the form of the material can influence its properties and
`the biological response to its implantation.
`6. To understand how electron structure contributes to various types of bonding.
`
`Introduction to Biomaterials
`1.1
`This chapter is designed to provide a general overview of the breadth of the field of
`biomaterials and discuss briefly all the aspects of this discipline that will be explored
`more fully in later chapters. In addition, it provides important basic definitions and
`background information for the remainder of the book. The chapter begins with a
`discussion of the scope and history of biomaterials science and the role of the bio(cid:173)
`materialist. In later sections, degradative, surface and bulk properties of materials
`are related to the choices incumbent upon biomaterialists as they design/select the
`optimal material for particular applications. Finally, a review of basic chemical prin(cid:173)
`ciples underlying important material properties is presented.
`
`1.1.1 Important Definitions
`
`Biomaterials is a wide-ranging field, encompassing aspects of basic biology, medicine,
`engineering, and materials science, that has developed to its current form primarily
`
`1
`
`2 of 32
`
`

`

`2 Chapter 1 Materials for Biomedical Applications
`
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`since World War II. Because of the breadth of the field, confusion often exists about
`what a biomaterial is, and, in particular, the role of the biomaterialist in modern
`medicine. Therefore, we begin our discussion of biomaterials science with key defini(cid:173)
`tions to better characterize the discipline.
`According to a consensus decision by a panel of experts, a biomaterial is
`
`A material intended to interface with biological systems to evaluate, treat, augment,
`or replace any tissue, organ or function of the body [1].
`
`Therefore, biomaterials science is the study of biomaterials and their interactions
`with the biological environment [2] . This includes subjects relating to materials sci(cid:173)
`ence, such as mechanical properties of materials or surface modification of implants,
`as well as biological topics such as immunology, toxicology, and wound healing
`processes.
`Regardless of which aspect of biomaterials science is addressed, the "bio" of
`"biomaterial" cannot be forgotten. Because the overall goal of the field is the devel(cid:173)
`opment of materials that will be implanted in humans, one of the most important
`concepts in biomaterials science is that of biocompatibility. According to another
`consensus definition, biocompatibility is
`
`The ability of a material to perform with an appropriate host response in a specific
`application [1].
`
`Thus, a biomaterialist, as a practitioner of biomaterials science, is responsible for alter(cid:173)
`ations to the composition of a biomaterial and/or its fabrication process in order to
`control the biological response and produce an implant with maximal biocompatibili(cid:173)
`ty. As the above definitions indicate, a biomaterialist must consider both the material
`properties and the biological reaction to ensure that the chosen material is appropriate
`for the given application. Therefore, this book will address both the materials science
`(Chapters 1-7) and the biological (Chapters 8-14) aspects of biomaterials, with the goal
`of introducing principles to guide future biomaterialists in the selection and develop(cid:173)
`ment of optimal materials for a wide variety of applications and implantation sites.
`
`EXAMPLE PROBLEM 1.1
`
`Are the following items biomaterials? Why or why not?
`
`(a) contact lens
`(b) splinter
`(c) vascular graft
`(d) crutches
`
`Solution:
`"A biomaterial is a material intended to interface with biological systems to eval(cid:173)
`uate, treat, augment, or replace any tissue, organ or function of the body [1] ." (a) and (c) are
`biomaterials according to this definition. (a) interfaces with the ocular environment to aug(cid:173)
`merit the light-focusing function of the eye for vision. Similarly, (c) interfaces with the vascu(cid:173)
`lar environment to replace vascular (venous/arterial) function . (b) is not intended to interface
`with the biological environment or to serve a biological function. (d) could be viewed either
`as a biomaterial or not by the given definition. It depends upon the justification of the terms
`•
`"augment," "replace," and "interface."
`
`1.1.2 History and Current Status of the Field
`
`Although we consider biomaterials a relatively young field, its origins date back
`thousands of years. Archaeologists have uncovered remains of humans containing
`
`3 of 32
`
`

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`1.1
`
`Introduction to Biomaterials
`
`3
`
`metal dental implants from as early as 200 A.D., and it is known that linen was used
`as a suture material by the Egyptians. However, the development of the biomaterials
`field significantly increased after World War II with the widespread avail-ability of
`synthetic materials that were originally designed for use in the war. [3]
`For example, implantation of plastics (synthetic polymers) in humans was first
`reported in the 1940s. Many of these first attempts centered around poly(methyl
`methacrylate), which had been previously employed as a material for aircraft, and
`nylon, a common parachute material. However, the field progressed quickly from
`these first materials to encompass a wide range of material types. The two decades
`after World War II saw the advent, among others, of the first successful artificial hip
`(metallic biomaterials), kidney dialysis machines (originally using a natural polymer
`derivative, cellulose), and vascular grafts (another naturally derived polymer, silk). [3]
`The long-term success of these devices was due, in addition to the advancement
`in materials, to better surgical techniques, including proper sterilization, and patient
`monitoring. Also, a greater knowledge of biology, particularly as it related to bio(cid:173)
`compatibility, had a significant impact on the field of biomaterials. Although in the
`first few decades after World War II any material could be placed in a patient in an
`emergency situation, the need for biomaterial regulation was soon recognized, and
`national and international standards requiring rigorous testing before implantation
`were developed. [3]
`Today, biomaterials represent a significant portion of the healthcare industry,
`with an estimated market size of over $9 billion per year in the United States (see
`Table 1.1). Some of the most common medical devices that possess a large biomate(cid:173)
`rial component include replacement heart valves, synthetic vascular grafts, hip and
`knee replacements, heart-lung machines, and renal dialysis equipment.
`In the cardiovascular area, approximately 100,000 replacement heart valves [2]
`and 300,000 vascular grafts are implanted each year in the United States. Figure 1.1
`depicts one typical design of a heart valve, while synthetic vascular grafts are shown
`in Figure 1.2. After insertion, both of these devices can restore proper blood flow
`and thus greatly improve the patient's ability to function normally. However, anum(cid:173)
`ber of problems can occur. For replacement heart valves, the most common compli(cid:173)
`cations include blood clotting, mechanical failure, and infection (see Fig. 1.3) . In
`vascular grafts, blood clotting or overgrowth of tissue that blocks the interior of the
`vessel and prevents blood flow can be causes for device failure.
`
`Figure 1.1
`Image of a bileaflet heart valve
`prosthesis. (Reprinted with
`permission from [2])
`
`4 of 32
`
`

`

`4 Chapter 1 Materials for Biomedical Applications
`
`TABLE 1.1
`
`Biomaterials in the U.S. Healthcare Market
`
`Total U.S. health care expenditures (2000)
`Total U.S. health research and development (2001)
`Number of employees in the medical device industry (2003)
`Registered U.S. medical device manufacturers (2003)
`Total U.S. medical device market (2002)
`U.S. market for disposable medical supplies (2003)
`U.S. market for biomaterials (2000)
`Individual medical device sales:
`Diabetes management products (1999)
`Cardiovascular devices (2002)
`Orthopedic-musculoskeletal surgery
`U.S. market (1998)
`Wound care U.S. market (1998)
`In vitro diagnostics (1998)
`Numbers of devices (U.S.):
`Intraocular lenses (2003)
`Contact lenses (2000)
`Vascular grafts
`Heart valves
`Pacemakers
`Blood bags
`Breast prostheses
`Catheters
`Heart-lung (Oxygenators)
`Coronary stents
`Renal dialysis (number of patients, 2001)
`Hip prostheses (2002)
`Knee prostheses (2002)
`Dental implants (2000)
`(Reprinted with permission from [2])
`
`$1,400,000,000,000
`$82,000,000,000
`300,000
`13,000
`$77,000,000,000.
`$48,600,000,000
`$9,000,000,000
`
`$4,000,000,000
`$6,000,000,000
`$4,700,000,000
`
`$3,700,000,000
`$10,000,000,000
`
`2,500,000
`30,000,000
`300,000
`100,000
`400,000
`40,000,000
`250,000
`200,000,000
`300,000
`1,500,000
`320,000
`250,000
`250,000
`910,000
`
`Figure 1.2
`Image of vascular grafts
`constructed of expanded poly
`( tetrafluoroethylene).
`(Reprinted with permission
`from [4])
`
`5 of 32
`
`

`

`·ff. . '
`
`1.1
`
`Introduction to Biomaterials
`
`5
`
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`
`Over 500,000 artificial joint replacements, such as the knee or hip, are implant(cid:173)
`ed yearly in the United States [2] . An example of an artificial hip is shown in Figure
`1.4. Such replacements restore the ability to walk, or even engage in moderate ath(cid:173)
`letic activity, and thus greatly improve the patient's quality of life. Over time, how(cid:173)
`ever, these prostheses can loosen, leading to tissue damage and creating the need for
`a second surgery to repair or replace the implant.
`Heart-lung machines, like that seen in Figure 1.5, are used daily in operating
`rooms worldwide to recirculate blood externally, allowing a patient's heart to be
`stopped so that surgery can be performed on it. Although the development of such
`devices was crucial to the field of cardiac surgery and saves the lives of many pa(cid:173)
`tients each year, certain problems remain. Due in part to the limitations of the cur(cid:173)
`rent biomaterial filters, the heart-lung machine is unable to attain the efficiency of
`the native lung for blood oxygenation. This, in turn, requires higher pumping pres(cid:173)
`sures than are normally exerted by the heart, which can lead to blood cell lysis
`(breakage). In addition, anticoagulants are required to prevent blood clotting, there(cid:173)
`by increasing the risk of uncontrolled bleeding after surgery.
`Approximately 300,000 patients in the United States with compromised kidney
`function must receive renal dialysis three times per week [5] to remove waste from
`the blood in order to maintain life. In this procedure, the blood is pumped across a
`dialysis membrane, which allows waste products of certain size to flow out of the
`blood (see Fig. 1.6). However, this device suffers from problems similar to those de(cid:173)
`scribed for the heart-lung machine, including blood cell lysis, and the potential for
`infection or undesired activation of a portion of the body's immune response (the
`complement system, discussed in Chapter 12).
`
`1.1.3 Future Directions
`
`Over the course of the past 50 years, several stages in biomaterials development can
`be identified. Starting in the 1960s-1970s, the first generation of biomaterials was
`designed to be inert, or not reactive with the body, thereby decreasing the potential
`for negative immune response to the implant. In the 1990s, this concept was gradu(cid:173)
`ally replaced with a second generation of materials designed to be bioactive, inter(cid:173)
`acting in a positive manner with the body to promote localized healing.
`Because biomaterials science occupies a unique niche at the corner of several
`disciplines, advances in disparate subjects have propelled the field to its current status.
`Experiments providing detailed knowledge of cell and molecular biology and genet(cid:173)
`ics have led to the development of these "smart" or "instructive" materials, which
`can help guide the biological response in the implant area. Advances in surgical
`
`Figure 1.3
`Image of blood clots on a
`bileaflet
`heart
`valve.
`(Reprinted with permission
`from [6])
`
`..
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`
`6 of 32
`
`

`

`6 Chapter 1 Materials for Biomedical Applications
`
`t Metallic outer socket
`
`Figure 1.4
`An orthopedic hip implant,
`exhibiting the use of all three
`classes of biomaterials: met(cid:173)
`als, ceramics and polymers.
`In this case, the stem, which
`is
`implanted
`in the femur
`(upper bone of the leg), is
`made with a metallic bioma(cid:173)
`terial. The implant may be
`coated with a ceramic to
`improve attachment to the
`bone, or a polymeric cement
`(not shown) can be used to
`hold the stem in place. At the
`top of the hip stem is a ball
`(metal or ceramic) that works
`in conjunction with the corre(cid:173)
`sponding socket to facilitate
`motion in the joint. The cor(cid:173)
`responding inner socket is
`made out of either a polymer
`(for a metallic ball) or ceram(cid:173)
`ic (for a ceramic ball), and
`attached to the pelvis by a
`metallic socket.
`(Adapted
`with permission from [7])
`
`Polymeric or
`ceramic inner socket -
`
`I
`
`Ceramic coating 1
`
`Metallic
`
`techniques like minimally invasive surgery have promoted the design of injectable
`materials that can be applied locally and with minimal pain to the patient. New de(cid:173)
`velopments in materials science, such as composites involving nano-scale objects as
`reinforcing agents, have inspired the creation of a new set of nano-structured bio(cid:173)
`materials.
`Further advances in all of these fields are expected to have a great impact on the
`future of biomaterials. Thus, as we move forward in the new millennium, we stand
`on the edge of another generation-biomaterials that are designed to become com(cid:173)
`pletely integrated and cause the full reproduction of damaged tissue, as exemplified
`
`Heat exchanger
`
`Figure 1.5
`Schematic of a heart-lung ma(cid:173)
`chine setup. (Reprinted with
`permission from [5].)
`
`Patient
`
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`pump
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`7 of 32
`
`

`

`1.2 Biological Response to Biomaterials
`
`7
`
`Figure 1.6
`Schematic of kidney dialysis
`setup. (Reprinted with per(cid:173)
`mission from [5])
`
`tble
`de(cid:173)
`s as
`)10-
`
`the
`and
`)m(cid:173)
`fied
`
`in current research in biomaterials for tissue engineering applications. The perpetu(cid:173)
`al evolution of new processes and materials makes the field of biomaterials very dy(cid:173)
`namic. This book is therefore designed to relate basic principles in biology and
`materials science to both currently used materials as well as potential design param(cid:173)
`eters for the next generation of biomaterials.
`
`1.2 Biological Response to Biomaterials
`One of the major concerns of the biomaterialist is the biological response to the cho(cid:173)
`sen material, which determines its biocompatibility. Immediately after implantation,
`inflammation usually occurs. Clinically, this is characterized by redness, swelling,
`warmth, and pain around the implant site. However, this is usually temporary, and
`may be resolved in a number of ways, including complete integration of the materi(cid:173)
`al into the surrounding tissue or isolation of the implant with fibrous encapsulation.
`Depending on the implant site and the nature of the material, other reactions may
`also ensue, such as activation of the immune system, localized blood clotting, infec(cid:173)
`tion, tumor formation, or implant calcification. Although many of these responses are
`not desirable, certain reactions may be acceptable, depending on the application. For
`example, calcification of an implant used to support bone tissue may be necessary to
`ensure good integration between the biomaterial and the surrounding bone.
`Factors such as the type of material, the shape of the implant, material degradation
`characteristics, surface chemical properties, and bulk chemical and mechanical proper(cid:173)
`ties have been identified as important to the overall biocompatibility of a biomaterial
`and to its suitability for specific applications. Therefore, the biomaterialist must select
`the material type and processing method to obtain optimal degradative, surface, and
`bulk characteristics, keeping in mind the final location and application of the implant.
`At the most basic level, it is the protein and cellular response to the material that
`determines the overall success of the implant. Therefore, characterization of these
`responses is necessary. Experiments assessing both cell/protein interactions with bio(cid:173)
`materials and overall biocompatibility can be carried out either in vitro or in vivo.
`In vitro (literally "in glass" [1]) tests take place in a well-controlled laboratory envi(cid:173)
`ronment, while in vivo experiments require biomaterial implantation in a living sys(cid:173)
`tem, such as an animal model [1].
`
`EXAMPLE PROBLEM 1.2
`The biological response to a material is of utmost concern to a biomaterialist. The response
`must be appropriate for the desired application. For example, calcification of implant materials
`
`8 of 32
`
`

`

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`
`8 Chapter 1 Materials for Biomedical Applications
`
`.
`
`..,
`
`.
`
`for bone applications is often sought for proper integration of the implant with the surrounding
`bone tissue. Would calcification of an artificial heart valve composed of decellularized
`porcine (pig) pericardium be a favorable biological response? Why or why not?
`
`Solution: No. Heart valves serve to ensure proper fluid flow patterns in the heart, so that
`blood can be pumped to perfuse the periphery. Consequently, heart valves must be flexible
`and durable to properly open and closely cyclically. Calcification leads to undesired stiffness
`of the material in this case that will impede the function of the valve (opening/closing) and de(cid:173)
`crease the efficiency of cardiac output.
`•
`
`1.3 Biomaterial · Product Testing and
`FDA Approval
`The ultimate in vivo event takes place upon final device implantation in humans.
`However, due to ethical concerns, before this can occur, many in vitro and in vivo
`biocompatibility tests must be performed. These are dictated by and analyzed in ac(cid:173)
`cordance with standards compiled by agencies such as the ASTM International
`(ASTM) and the International Organization for Standardization (IS0). 1 These
`agencies are responsible for the development of technical standards for materials,
`products, systems, and services. More specifics on these guidelines are found in later
`sections of this book.
`The steps to producing a product involving a biomaterial are outlined by regulato(cid:173)
`ry agencies such as the U.S. Food and Drug Administration (FDA). Approval by this
`agency is required in order to sell a biomedical product in the United States. Biomedical
`product development generally includes the following stages (adapted from [8]}:
`
`1. In vitro testing
`2. In vivo studies with healthy experimental animals
`3. In vivo studies with animal models of disease (if applicable)
`4. Controlled clinical trials
`
`Results from all of these tests are reported to the FDA to prove that the new de(cid:173)
`vice is both safe and effective. The amount of testing and whether or not clinical tri(cid:173)
`als are required depends on the perceived danger of the proposed product. Based on
`their intended use, products are classified as Class I, II, or III [9]. Class III devices are
`more complicated and perform tasks more directly related to saving or sustaining
`life. Thus, they are subject to the most rigorous standards, including, usually, there(cid:173)
`quirement of clinical trials. It is also important to note here that the FDA approves
`devices, not materials, so currently, specific biomaterials can only be used in the con(cid:173)
`text of approved final devices.
`
`1.4 Types of Biomaterials
`One of the primary roles of the biomaterialist is to choose the appropriate source of
`material for a specific application. In general, materials are classified as organic if
`they contain carbon or inorganic if they do not. More specifically, biomaterials fall
`into one of three categories of materials: metals, ceramics, or polymers.
`
`1 ASTM International was originally the American Society for Testing and Materials. Also, ISO is derived
`from the Greek word "isos" due to variations in the translation of International Organization for
`Standardization.
`
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`9 of 32
`
`

`

`TABLE 1.2
`
`Metals Commonly Used in Biomedical Applications
`
`Metal
`Cobalt-chromium alloys
`
`Gold and platinum
`Silver-tin-copper alloys
`Stainless steel
`
`Titanium alloys
`
`Applications
`Artificial heart valves, dental prostheses, orthopedic
`fixation plates, artificial joint components,
`vascular stents
`Dental fillings, electrodes for cochlear implants
`Dental amalgams
`Dental prostheses, orthopedic fixation plates,
`vascular stents
`Artificial heart valves, dental implants, artificial
`joint components, orthopedic screws, pacemaker
`cases, vascular stents
`
`1.4.1 Metals
`Metals are inorganic materials possessing non-directional metallic bonds with high(cid:173)
`ly mobile electrons (see Section 1.7 for more on bond types). A list of metals and al(cid:173)
`loys (combinations of multiple elemental metals) commonly used in biomedical
`applications is found in Table 1.2. In addition to their ability to conduct electricity,
`metals are strong and relatively easily formed into complex shapes. This makes met(cid:173)
`als a suitable material for orthopedic (hip and knee) replacements (Fig. 1.4 ), for
`dental fillings and implants for craniofacial restoration, and for cardiovascular ap(cid:173)
`plications such as stents and pacemaker leads.
`
`'1.4.2 Ceramics
`Ceramics are inorganic materials composed of non-directional ionic bonds be(cid:173)
`tween electron-donating and electron-accepting elements. Ceramic materials most
`often employed as biomaterials are listed in Table 1.3. Ceramics may contain crys(cid:173)
`tals, like metals, or may be non-crystalline (amorphous) glasses. Ceramics are very
`hard and more resistant to degradation in many environments than metals.
`However, they are quite brittle because of the nature of ionic bonds. Due to the
`similarity between the chemistry of ceramics and that of native bone, ceramics are
`most often used as a part of orthopedic implants or as dental materials (Fig. 1.4 ).
`Because of their brittle nature, they are commonly employed in applications re(cid:173)
`quiring small loads.
`
`TABLE 1.3
`
`Ceramics Commonly Used in Biomedical Applications
`
`Ceramic
`Aluminum oxides
`
`Bioactive glasses
`
`Calcium phosphates
`
`Applications
`Orthopedic joint replacement components, orthopedic
`load-bearing implants, implant coatings,
`dental implants
`Orthopedic and dental implant coatings,
`dental implants, facial reconstruction components,
`bone graft substitute materials
`Orthopedic and dental implant coatings,
`dental implant materials, bone graft substitute
`materials, bone cements
`
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`
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`10 of 32
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`

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`10 Chapter 1 Materials for Biomedical Applications
`
`Figure 1.7
`Chemical structure of poly
`(methyl methacrylate), a poly(cid:173)
`mer commonly used as a bone
`cement. (a) shows a section
`of the polymer chain, with
`the dotted lines indicating
`the repeating unit, which is
`also shown in (b).
`
`(a)
`
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`1.4.3 Polymers
`Unlike the other two classes of biomaterials, polymers are organic materials pos(cid:173)
`sessing long chains that are held together by directional covalent bonds (Fig. 1. 7).
`Polymers are widely used in biomedical applications (Fig. 1.4) due to the range of
`physical and chemical properties possible with these materials [10]. Examples of
`some of the synthetic (man-made) polymers that are often used as biomaterials are
`found in Table 1.4. Alternatively, polymers that are derived from natural sources,
`such as proteins commonly found in the body, have been widely explored as bio(cid:173)
`materials. Common uses for these types of polymers are also listed in Table 1.4.
`Regardless of the origin of the polymer, there are several polymer sub-classes
`that are useful to the biomaterialist in that each may be particularly suited to certain
`
`TABLE 1.4
`
`Synthetic and Naturally Derived Polymers Commonly Used in Biomedical
`Applications
`
`Polymer
`Synthetic
`Poly(2-hydroxyethyl methacrylate)
`Poly( dimethyl siloxane)
`
`Poly( ethylene)
`Poly(ethylene glycol)
`Poly( ethylene terephthalate)
`Poly( e-caprolactone)
`Poly(lactic-co-glycolic acid)
`Poly(methyl methacrylate)
`Poly( tetrafl uoroethylene)
`Poly( isoprene)
`Poly(propylene)
`Naturally derived
`Alginate
`Chitosan
`Collagen
`
`Elastin
`Fibrin
`Glycosaminoglycan
`Hyaluronic acid
`
`Applications
`
`Contact lenses
`Breast implants, contact lenses, knuckle
`replacements
`Orthopedic joint implants
`Pharmaceutical fillers, wound dressings
`Vascular grafts, sutures
`Drug delivery devices, sutures
`Resorbable meshes and sutures
`Bone cements, diagnostic contact lenses
`Vascular grafts, sutures
`Gloves
`Sutures
`
`Wound dressings
`Wound dressings
`Orthopedic repair matrices, nerve repair
`matrices, tissue engineering matrices
`Skin repair matrices
`Hemostatic products, tissue sealants
`Orthopedic repair matrices
`Orthopedic repair matrices
`
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`
`11 of 32
`
`

`

`1.4 Types of Biomaterials
`
`11
`
`tissue types. For example, elastomers can sustain substantial deformation at low
`stresses and return rapidly to their initial dimensions upon release of the stress [1],
`suggesting that they may be suitable for cardiovascular applications, where tissue
`elasticity is an important property. Another category of polymers called hydrogels
`exhibit the ability to swell in water and to retain a significant fraction of water with(cid:173)
`in their structures without completely dissolving [1]. Due to their high water con(cid:173)
`tent, hydrogels have been explored for a variety of soft tissue applications.
`It is also possible to form composite materials to improve bulk or surface proper(cid:173)
`ties of biomaterials. Composites are materials consisting of two or more chemically
`distinct components, one of which is often a polymer [11]. Composites are often creat(cid:173)
`ed to optimize mechanical properties. In this case, a fiber-reinforcing material (usually
`carbon) is dispersed throughout a polymer. Although a detailed discussion of compos(cid:173)
`ite materials is beyond the scope of this text, it is interesting to note that many consid(cid:173)
`er the structure of human tissues to resemble a fiber-reinforced composite.
`
`1.4.4 Naturally Derived vs. Synthetic Polymers
`Naturally based polymers can be derived from sources within the body (collagen,
`fibrin, or hyaluronic acid) or outside the body (chitosan, alginate). One of the most
`common natural biomaterials found in the human body is the protein collagen.
`Many different types of collagen exist in various tissues, and several of these, par(cid:173)
`ticularly types I and II, have been explored as biomaterials. Another protein-based
`material, fibrin, results from the combination of the blood clotting factors fibrino(cid:173)
`gen and thrombin. Both collagen and fibrin have been used in tissue engineering at(cid:173)
`tempts to repair cartilage defects and in other orthopedic applications.
`In addition to proteins, naturally based polymers may be derived from sugars
`(carbohydrates). Hyaluronic acid is an example of a carbohydrate molecule occurring
`in human tissues that is often employed as a biomaterial. However, the source of
`other carbohydrate-derived materials may be non-human. Chitosan, a sugar-based
`substance found in arthropod exoskeletons; agarose, which is formed by algae; and
`alginate, derived from seaweed, are all currently being investigated as biomaterials
`for a variety of applications. For example, a combination of chitosan and alginate
`has been examined for wound dressings.
`There are advantages and disadvantages to both natural and synthetic poly(cid:173)
`mers, and particular materials may lend themselves to certain applications over oth(cid:173)
`ers. In many cases, naturally derived polymers have chemical compositions similar
`to the tissues they are replacing. Therefore, they may be more fully integrated into
`the surrounding tissue over time or more easily altered (remodeled) in response to
`changes in tissue needs. However, concerns exist about the feasibility of finding
`large amounts of some of these materials for clinical applications, their relatively low
`mechanical properties, and the assurance of pathogen removal. In addition, regions
`of these molecules may be recognized as "foreign" by the body's immune system,
`leading to a type of material "rejection." Further potential problems arise when the
`biomaterial is based on not a single naturally occurring polymer, but decellularized
`tissue. Here, unwanted calcification leading to device failure (discussed in Chapter 14)
`is a particular concern.
`In contrast, synthetic polymers can be easily mass-produced and sterilized, so
`supply issues are not a problem. Additionally, their physical, chemical, mechanical
`and degradative properties can be tailored for specific applications. However, un(cid:173)
`less specifically treated, most synthetic materials do not interact with tissues in an
`active manner and therefore cannot direct or aid in healing around the implant
`site. Also, few synthetic polymers have been approved by regulatory agencies for
`use in humans in specific applications.
`
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`
`12 of 32
`
`

`

`12 Chapter 1 Materials for Biomedical Applications
`
`Regardless of source, all of the materials described in this section are polymeric, so
`they have a number of key properties in common and can all be modified or processed
`using similar techniques. Therefore, in the following chapters, the term "poly