Chapter 1
Introduction to Biomaterials
Susmita Bose and Amit BandyopadhyayW. M. Keck Biomedical Materials Research Lab, School of Mechanical and Materials
Engineering, Washington State University, Pullman, WA, USA
Ch
Cop
Chapter Outline
1.1. Introduction
11.2. Types of Materials 2
1.3. Biomaterials and
Biocompatibility 4
1.4. Types of Biomaterials 5
1.5. Properties of Biomaterials 6
aracterization of Biomaterials. http://dx.doi.org/10.1016/B9
yright � 2013 Elsevier Inc. All rights reserved.
1.6. Biomaterials
Characterization and Outline
of this Book
81.7. Summary 9
Suggested Further Reading 9
1.1. INTRODUCTION
With the evolution of human civilization, the field of biomaterials evolvedinvolving different materials at multiple length scales from nano- to micro- tomacrolevel with a simple focus to extend human life and improve the quality oflife. Over 1000 years back, silver in different forms was used as an antimi-crobial agent to prevent infection. Different types of surgical procedures canalso be found during early stages of civilization. However, probably the mostsignificant developments took place in the field of biomaterials over the years1901–2000. Artificial joints improved the quality of life for millions of peopleover the past 60 years, resorbable sutures simplified surgical procedures, anddifferent cardiovascular devices saved millions of lives, just to name a few. Theadvent of tissue engineering and organ regeneration is pushing the frontiers ofscience today to make the years 2001–2100 more exciting in the fieldof biomaterials. However, to appreciate the benefits, it is not just the design ofbiomaterials that is important, but sound engineering design and appropriatematerials and device characterization are also needed. Moreover, fora biomedical device to see the commercialization light, it is also important tocarry out testing following appropriate standards to get regulatory approval.Overall, benefits of biomaterials research can only be appreciated when these
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2 Characterization of Biomaterials
materials are characterized well at both the materials level and the device levelfollowing regulatory guidelines. Considering the multidisciplinary nature of thefield, it is also not easy to carry out large variety of experiments using differenttechniques. Realizing this problem in biomaterials characterization, we havedeveloped this book to offer an insight on various characterization toolsfocusing on biomaterials and biomedical devices.
1.2. TYPES OF MATERIALS
Materials can be classified into different groups based on their crystal structure,bonding, and macrostructures. Each subgroup of materials shows somewhatsimilar properties and then those materials can be clubbed together to study theirperformance for different applications. If we look at types of bonding, materialscan be classified into three broad categoriesdmetals, ceramics and polymers.Materials that are bonded via metallic bonds are called metals. Due toabundance of free electrons in metallic bonds, metals are both thermally andelectrically conductive, and show malleability in terms of their mechanicalproperties. Materials that are primarily ionic and/or covalently bonded are calledceramics. Since ionic and covalent bonds do not offer any free electrons,ceramics are generally nonconducting materials both thermally and electrically.However, due to the movements of defects, some ceramics show conductivity athigher temperature. Materials that are based on long carbon chain and cova-lently bonded with some secondary bonding are polymers, where “mers” orunits are connected in the long range. Due to covalent bonding, most polymersare nonconducting. When any three of these main materials are mixed togetherwithout losing its inherent characteristics, then we form a new class of materials,called composites. Some examples of natural composites are wood and bone.
When we look at the unit cell, the basic building block of any material, wecan classify materials into three groupsdcrystalline, semicrystalline andamorphous. If the unit cell is repeated in all three directions and maintainsa long-range order, then those materials are called a crystalline material such asiron, titanium, chromium or polycrystalline ceramics. The basic unit cell,defined by the three-dimensional shape and atom positions, can be for examplebody centered cubic or face centered cubic or hexagonal close packed (hcp),where “cubic” or “hexagonal” are crystal systems defined by the shape of theunit cell and “body centered” or “face centered” are specific atom positions thatdefines the Bravais lattice of the unit cell. These kinds of simple structures arecommon for most metallic systems, which are mainly crystalline in nature. Formany materials, unit cell does not repeat itself in three dimension for longrange, but only shows short-range repetition. Those materials with short-rangeordering of unit cells are called amorphous materials or glass. Due to lack ofordering, glassy materials show unique properties such as glass transitiontemperature (Tg), where a liquid phase transforms to a solid rubbery phase.There are also a group of materials that are partially glassy and partially
3Chapter j 1 Introduction to Biomaterials
crystalline. Those materials are called semicrystalline materials. Among others,many polymeric materials show semicrystalline nature.
Materials can also be classified as natural or synthetic. Natural materials arethose which are available in nature such as wood, rocks, corals and bones. Mostnatural materials are ceramics, polymers and their composites. Mother Naturedesigned these materials for a variety of purposes such as sensors, reservoirs,structural support or energy converters. Most of these materials have complexchemistry and structure and the mankind is still exploring those to enrich theirlearning. Synthetic materials are man-made materials designed for specificfunctionality. These materials include metallic materials such as steels forfracture management devices, to titanium and its alloys for implant, to poly-mers for ocular lenses and to ceramics for bone-tissue engineering. Syntheticmaterials are tailored for specific chemistry and structure for properties that canbe utilized to improve our everyday life. Once processed, their physical,chemical, mechanical and sometimes biological property determination isnecessary based on application need.
Materials can also be classified based on their macrostructures such asdense or porous. Most natural materials such as rocks, tissues, wood are porousmaterials. Porosity in these materials can serve various purposes. Most ceramicmaterials have residual porosity. Porosity can be nonuniform and vary in sizeand distribution. Porosity in materials can vary from 1% to 10% such as incortical bone to as high as >70% in some cancellous bones. Because ofporosity, these materials are lighter weight, and many times show nonuniformproperties at different directions. However, it is very difficult to mimic suchnatural materials in terms of composition, structure and properties. Whenmaterials do not show any porosity, those are called dense materials. Mostmetallic materials are dense in nature with residual porosity <1%. Densematerials are typically isotropic in nature and can be shaped easily by variousforming techniques.
Figure 1.1 schematically shows different types of materials. Any onematerial can also fall into many of these categories. For example, bone isa natural material, that is porous, and a ceramic–polymer composite.
Types of materials
Metals
Polymers
Ceramics
Composites Amorphous
Crystalline
Semicrystalline
Synthetic
Natural
Porous
Dense
FIGURE 1.1 Different types of materials.
4 Characterization of Biomaterials
1.3. BIOMATERIALS AND BIOCOMPATIBILITY
A biomaterial is a material, synthetic or natural, that can be used in medicalapplications to perform a body function or replace a body part or tissue.A biomaterial is intended to interact at the interface of biological systems. It mayalso be used as a delivery system for drug or biological factor. Biomaterials aredesigned based on application needs. Reaching back to the beginnings of civi-lization, the Romans, Aztecs and Chinese used gold in dental applications. TheMayans were found to have fashioned dental implants out of sea shells withresults indicating actual bone integration. A biomaterial must be biocompatible,i.e., it should be friendly to biological system and not do any harm to the system,whether at the cellular level or at the system level. A biocompatible materialshould elicit appropriate host response or able to perform its intended function ina specific application without the presence of adverse reactions. This is anemerging paradigm that requires and pushes unique multidisciplinary bound-aries based on understanding and integration of concepts from various broadfields, but not limited to, chemistry, biology, materials science, mechanical,chemical and electrical engineering as well as medicine.
Biomaterials are used to augment, repair or replace any tissue, organ, orfunction of the body that has been lost through trauma, disease or injury. Recentpractice in medicine often times uses tissue reconstruction using autograft,where tissue graft or organ transplant from one point to another of the sameindividual takes place. However, limited availability, donor site morbidity andabove all, the need for a second surgery restrict their application. On the otherhand, potential alternative is the use of allograft, i.e. tissue graft or organtransplant from a donor of the same species as the recipient. The other alter-native could be xenograft, which is tissue graft or organ transplant from a donorof a different species from the recipient. Both allograft and xenograft use aresomewhat restricted due to the immunogenic response and they may imposeadverse biocompatibility in patients’ body. These reasons draw our attention tothe biomaterials that are available from other sources, which could be syntheticor natural. It was not until the turn of the twentieth century, modern biomate-rials and their potential applications began to take shape. These first-generationmodern biomaterials are mainly focused on basic functionality andbiocompatibility.
Since early 1900s, metal plates were used to stabilize long bone fractureswith the hopes of faster and more functional healing. By the 1930s, full jointreplacement surgeries were being performed with varying degrees ofsuccess. The invention and widespread use of synthetic plastics createda boom in the biomaterials industry resulting in devices such as syntheticheart valve (metal cage surrounding a silicone elastomer ball) and total hiparthroplasty systems (ultrahigh molecular weight polyethylene). Some otherimportant inventions in this era include the intraocular lenses (poly(methylmethacrylate)dPMMA) and the desk-sized pacemaker.
5Chapter j 1 Introduction to Biomaterials
Further understanding of the complexities of biology ushered in the nextgeneration of biomaterials beginning in the 1960s. Scientists and engineersbegan to design materials specifically for use in biomedical applications.The focus began to shift from materials that were simply biocompatible totechnologies that took into consideration the specific needs of the specificbiology. Many bioresorbable materials, those biomaterials resorbed in bio-logical system, were also created during this time. Some of the majoradvances in materials came in the form of synthetic polymers such as Teflon,which is still widely used today in various vascular grafting and surgicalapplications. Hydrogels lead to the invention of the soft contact lenses.Poly(lactic–glycolic acid) (PLGA) was developed for resorbable sutures.Plastic materials were not the only advances made during this time period.Ceramics such as calcium phosphate synthetic bone analogs were alsodeveloped. Today, these synthetic materials are used more often than auto-grafts (bone taken from another source on the patient’s body) or allografts(processed cadaver bones). Titanium alloys with better biocompatibilitywere developed as a lighter alternative to traditional stainless steel ortho-pedic implants.
1.4. TYPES OF BIOMATERIALS
Like any other materials, biomaterials can be grouped into four major cate-gories: (1) polymers, (2) metals, (3) ceramics, and (4) composites. Polymerscan be used in both soft and hard tissue applications, and comprise the largestclass of biomaterials. Polymers are also widely used in drug delivery appli-cations. Polymers could be natural (examples: collagen, sodium alginate, andcellulose) or synthetic (examples: silicone rubber, PMMA, poly(vinyl chlo-ride), and co-PLGA). Metals are mostly used for dental and orthopedicapplications. Most commonly used metals are Ti and its alloy, stainless steelsand Co–Cr alloy. Ceramics are mainly used in hard tissue repair, regenerationand augmentation, especially in nonload-bearing applications or as coatings onmetal implants. Most widely used ceramic biomaterials are calcium phosphates(CaP), alumina (Al2O3), and bioglass. Polymer–ceramic composite representsthe major part of composite biomaterials.
Biomaterials–tissue responses can be divided into four different types.(1) Toxic: toxic materials cause death to surrounding tissue. (2) Bioinert:this type of response is caused by nontoxic but biologically inactive mate-rials. Fibrous tissue encapsulation of the bioinert material is caused in vivo,which leads to the loosening and ultimate failure of the implant. This is mostcommonly seen in metallic implants. A bioactive material coating onmetallic implant may prevent fibrous tissue encapsulation. (3) Bioactive: thistype of response is seen if the material is nontoxic and biologically active.The term biologically active means that an interfacial bond forms betweenthe material and host tissue. Bioactive glasses, many types of polymers and
6 Characterization of Biomaterials
most calcium phosphate ceramics fall in this category. (4) Bioresorbable:this type of response is seen when a nontoxic material dissolves in vivo suchas calcium sulfate (plaster of paris), tricalcium phosphate, bioactive glassesand PLGA. As a result, the surrounding host tissue can replace the syntheticmaterial.
1.5. PROPERTIES OF BIOMATERIALS
There are many good books written on properties of materials. The purposeof this brief introduction on materials properties is only to make the readerfamiliar with the subject matter. Among various materials properties, themost important ones related to biomaterials are chemical, physical,mechanical, and biological in relation to their surface and bulk properties.Chemical properties deal with the chemistry of the materials such ascomposition, bonding and atomic structures. Physical properties deal withmicrostructures, phases, density and different types of porosity. Mechanicalproperties deal with strength and toughness of the materials along withhardness and different failure mechanisms. Biological properties deal withhow materials behave in a biological environment. If the biological envi-ronment is created in a Petri dish and properties are measured, then they arecalled in vitro properties; if the properties are measured inside an animal ora human body, then they are called in vivo properties. Surface properties dealwith properties of materials at the outer layer where all bonds are notsatisfied. Due to dangling bonds, surface properties are often quite differentfrom the bulk properties of materials. All these material properties are linkedwith chemistry, structure and processing of materials. For example, carbon isa material with very different properties depending on its bonding andstructure. If carbon is closely packed and fully covalently bonded, then itforms diamond, which is the hardest material known to mankind. However,if carbon forms an hcp structure with covalent bonding along with somesecondary bonding, then it forms graphite. Graphite is a soft material.Therefore, just chemistry alone does not reflect properties of materials.Similarly, even if the chemistry and the structure are the same, materialsprocessing will also have a significant impact on properties and performanceof a material. A ceramic body with high-purity calcium phosphate can havestrength values varied significantly depending on the residual porosity in thepart, which will be dependent directly on the processing condition. There-fore, understanding properties of materials requires an in-depth knowledgeof structure as well as processing of those materials.
In this context, it is also important to review advantages and disadvantagesof different materials systems. Such generic properties only guide materialsselection toward any specific application. For metallic system, the mainadvantage lies with ductility. Field of metallurgy is very rich due to longtradition. Apart from their high strength and toughness, metallic materials can
7Chapter j 1 Introduction to Biomaterials
be processed reliably due to thousands of years of experience. These materialsare inherently conductive and available worldwide. Naturally, most largeindustrial structures are made of metallic materials. Metals are widely used injoint replacement and bone fracture fixation. Metallic materials provide highstrength and resistance to fracture, and are designed to resist corrosion.In comparison to metals, ceramics are generally hard and offer low wear ratein vivo. Ceramics are resistant to microbial attack and strong in compression.Aluminum oxide, zirconium oxide, calcium phosphates and bioglasses aresome of the most commonly used ceramic biomaterials. The first twocompositions are widely used in load-bearing implants, and the last two areused as bioactive and bioresorbable ceramics in bone-tissue engineering and ascoatings on metal implants to enhance bioactivity. Different forms of carbonare also used in devices such as heart valves as coatings or in dialysis chamber.A large variety of polymers are also used as biomaterials. Polymers can beflexible or rigid, with low or high strength, and can be biodegradable or bio-inert. Synthetic polymers can be functionalized with different biomolecules,and processed via different methods to achieve a variety of structures. Amongothers, polymers are used in artificial joints, artificial skin, sutures, facialimplants and drug delivery devices.
Selection of materials for different biomedical devices is a complicatedprocess, which depends on many factors including but not limited to mechanicalloading requirements, chemical and structural properties, and biological prop-erties. Biomaterials are also used in tissue engineering and drug delivery.Different types of biomolecules and drugs can be carried to desired organ usingnanostructures and then released in a controlled manner. In addition, multi-functional systems can be achieved by engineering biomaterials. Magneticnanoparticles are examples of multifunctional biomaterials. Different drugs canbe loaded on magnetic nanoparticles and led to specific organ using externalmagnetic field. Some of these particles can also be used to enhance imagingcontrast in magnetic resonance imaging and computed tomography scans.
Contemporary materials have made yet another paradigm shift. Not only arematerials carefully designed to accommodate various physiological factors, butalso they are moving into the realm of bioactive responses. In short, thesematerials go leaps and bounds beyond the traditional sense of biocompatible byincorporating factors that elicit a positive biological interaction. These mate-rials focus on issues such as biofouling, regenerative medicine, controlledrelease of therapeutic substances and tissue/organ engineering. Although thesematerials have come a long way since the first steel plates used for fracturefixation, there are still many challenges to overcome. Biological requirementsshould be met for each application, and materials should be characterized tofulfill the needs. Human biology is very complex and we are just beginning tounderstand the intricate processes and interactions between synthetic materialsand our body. Figure 1.2 shows generic applications of different types ofbiomaterials.
Metals
Polymers Ceramics
Synthetic
biomaterials
Orthopedic implants Dental implants
Stents
Heart valves
Fracture
management
devices
Opthalmologic
devices
Breast implants
Sutures
Skin grafts
Bone grafts
Pacemaker
Ear implants Dental implants
FIGURE 1.2 Applications of biomaterials in different devices.
8 Characterization of Biomaterials
1.6. BIOMATERIALS CHARACTERIZATION AND OUTLINEOF THIS BOOK
From the previous discussion, it is clear that the field of biomaterials isinherently multidisciplinary. Researchers from physical sciences, engineeringsciences, biological sciences and medicine often flock together to work onbiomaterials toward improving human health. Therefore, it is very importantfor all to understand what to and how to characterize different biomaterials,which is the main theme of this book. It is also important to understand thatmany times, characterization of just biomaterials may not be enough, andfurther systems-level testing may be necessary to validate actual performanceof the device. Considering all those issues, this book is developed with specificemphasis toward characterization of biomaterials and biomedical devices fortheir physical, mechanical, surface, in vitro and in vivo biological properties.Special attention was given toward device-level characterization of orthopedicand cardiovascular implants.
Chapters dealing with physical, mechanical and surface properties ofbiomaterials are developed by researchers from physical and engineeringsciences. These chapters are focused on techniques that can reveal basicproperties such as atomic structures, bonding, chemical interactions, phaseidentification and transformation to strength and toughness measurements tounderstanding modifications at the surface level and their influence onmaterial properties. Most of these techniques are followed by biomaterialsresearchers during early stage of materials development toward certainapplications. The following chapters include in vitro and in vivo testing ofbiomaterials including microbial interactions and biofilm characterization.These levels of testing will be needed before a biomaterial can be considered
Chemical and
physical
properties
Mechanical
properties
Surface
properties
In vitro
biological
properties
In vivo
biological
properties
Biomaterials
characterization
Biomedical device
characterization
Techniques based on physical
and engineering sciences
Techniques based on biological
sciences and medicine
FIGURE 1.3 Schematic outline shows different properties related to biomaterials.
9Chapter j 1 Introduction to Biomaterials
for clinical trials or in actual device manufacturing. The final part of this bookdeals with device-level characterization with special emphasis on orthopedicand cardiovascular devices. Researchers with industrial product developmentbackground contributed toward these chapters. Figure 1.3 outlines howdifferent chapters are linked to understand properties of biomaterials andbiomedical devices.
1.7. SUMMARY
This brief introductory chapter provides a broad overview of materials,biomaterials and the need to understand different techniques to characterizebiomaterials. From this chapter, the reader can gain a perspective on how rest ofthe topics in different chapters are divided to fully comprehend this inherentlymultidisciplinary field. Application of appropriate characterization tools cannot only save time to fully evaluate different biomaterials, it can also makecommercial biomedical devices safer. In the long run, safer biomedical devicescan only reduce the pain and suffering of mankind, a dream that resonates withevery biomedical researcher.
SUGGESTED FURTHER READING
[1] Ratner BD, Hoffman AS, Schoen FJ, Lemons JE. Biomaterials science – an introduction to
materials in medicine. Academic Press; 2012.
[2] Hollinger Jeffrey O, editor. An introduction to biomaterials. 2nd ed. CRC Press; 2011.
[3] Robert Lanza, Robert Langer, Joseph Vacanti, editors. Principles of tissue engineering.
Associated Press.
[4] Burdick Jason A, Mauck Robert L, editors. Biomaterials for tissue engineering applications.
Springer; 2011.
