Integrated BiomaterialsScience
Edited by
ROLANDO BARBUCCIInteruniversity Research Center for Advanced Medical Systems (C.R.I.S.M.A.)andDepartment of Chemical and Biosystem Sciences and TechnologiesUniversity of SienaSiena, Italy
KLUWER ACADEMIC PUBLISHERS NEW YORK, BOSTON, DORDRECHT, LONDON, MOSCOW
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Contributors
Giovanni AbatangeloInstitute of Histology and EmbryologyFaculty of MedicineUniversity of Padova35121 Padova, Italy
Ron AlkalayOrthopaedic Biomechanics LaboratoryBeth Israel Deaconess Medical CentreBoston, Massachusetts 02215, United States
Luigi AmbrosioInstitute of Composite Materials Technology
C.N.R., and C.R.I.B.University of Naples “Federico II”80125 Naples, Italy
Emma AngeliniDipartimento di Scienza dei Materiali ed
Ingegneria ChimicaPolitecnico di Torino10129 Torino, Italy
Marcus K. H. AuthUniversitätskinderklinik, Abteilung
Allgemeine Kinderheilkunde mitSchwerpunkt, Neuropädiatrie, Klinikumder Universitäts-Gesamthochschule
Essen, Germany
Alfonso BarbarisiIstituto di Biochimica delle Proteine ed
EnzimologiaConsiglio Nazionale delle Richerche0072 Arco Felice, Napoli, Italy
Marc BollaLaboratoire de biomatériaux dentairesUFR OdontologieUniversité de Nice Sophia Antipolis04537 Nice Cedex 05, France
Paola BrunInstitute of Histology and EmbryologyFaculty of MedicineUniversity of Padova35121 Padova, Italy
Paolo CalicetiDepartment of Pharmaceutical SciencesUniversity of Padova35131 Padova, Italy
Angelo CaputoAdvanced Prosthodontics, Biomimetics and
Hospital Dentistry DepartmentUCLA School of DentistryLos Angeles, California 90095-1668,
United States
Marie-Paule CarrenoLaboratoire d’Immunopathologie HumaineINSERM U430, Hôpital Broussais75014 Paris, France
Gerardo CatapanoDepartment of Chemical and Materials
EngineeringUniversity of Calabria87036 Arcavacata di Rende (CS), Italy
Luigi CelliClinica Ortopedica e TraumatologicaUniversità degli Studi di Modena e Reggio
EmiliaDepartimento delle Discipline Chirurgiche e
delle Emergenze41100 Modena, Italy
Elisabetta CenniLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
vii
viii Contributors
Roberto ChiesaDipartimento di Chimica Fisica ApplicataPolitecnico di Milano20131 Milano, Italy
Krishnan K. ChitturChemical and Materials Engineering
DepartmentUniversity of Alabama at HuntsvilleHuntsville, Alabama 35899, United States
Gabriela CiapettiLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
Alberto CigadaDipartimento di Chimica Fisica ApplicataPolitecnico di Milano20131 Milano, Italy
Roberta CortiroInstitute of Histology and EmbryologyFaculty of MedicineUniversity of Padova35121 Padova, Italy
Stephen P. DenyerSchool of Pharmacy and Biomolecular
SciencesUniversity of BrightonBrighton, BN2 4GJ, United Kingdom
Alfredo De RosaIstituo di Biochimica delle Proteine ed
EnzimologiaConsiglio Nazionale delle Ricerche0072 Arco Felice, Napoli, Italy
Roberto De SantisInstitute of Composite Materials Technology
C.N.R., and C.R.I.B.University of Naples “Federico II”80125 Naples, Italy
Luca FambriDepartment of Materials EngineeringUniversity of Trento38050 Trento, Italy
Antonietta M. GattiINFM, Laboratorio dei BiomaterialiDipartimento di Discipline Chirurgiche e
delle EmergenzeUniversità di Modena e Reggio Emilia41100 Modena, Italy
Roberto GiardinoExperimental Surgery DepartmentCodivilla-Putti I.O.R. Research Institute40136 Bologna, Italy
Francisco-Javier GilCREB (Biomedical Engineering Research
Center)Department of Materials Science and
Metallurgical EngineeringUniversitat Politècnica de Catalunya08028 Barcelona, Spain
Maria-Pau GinebraCREB (Biomedical Engineering Research
Center)Department of Materials Science and
Metallurgical EngineeringUniversitat Politècnica de Catalunya08028 Barcelona, Spain
Donatella GranchiLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
Giuseppe GuidaIstituto di Clinica OrtopedicaUniversità di Napoli80138 Napoli, Italy
Franck J. HagegeLaboratoire de biomatériaux dentairesUFR OdontologieUniversité de Nice Sophia Antipolis04537 Nice Cedex 05, France
Richard T. HartDepartment of Biomedical EngineeringTulane UniversityNew Orleans, Louisiana 70118,United States
Kunihiro HisatsuneDepartment of Dental Materials ScienceNagasaki University School of DentistryNagasaki 852, Japan
Contributors ix
Yoshito IkadaResearch Center for Biomedical EngineeringKyoto UniversitySakyo-kuKyoto 606, JapanPresent address:Department of Medical ElectronicsFaculty of Medical EngineeringSuzuka University of Medical ScienceSuzuka City, Mie 510-0293, Japan
Kemal KesenciChemical Engineering Department and
Bioengineering DivisionHacettepe University, Beytepe06530 Ankara, Turkey
Jonathan C. KnowlesDepartment of Biomaterials-Eastman Dental
InstituteUniversity College LondonLondon WC1X8LD, United Kingdom
Adriano KrajewskiResearch Institute for Ceramic Technology of
the Italian National Research Council48018 Faenza (Ravena), Italy
Denis LabarreLaboratoire de Biomatériaux et PolymèresUMR CNRS 8612Université Paris-Sud XI92290 Châtenay-Malabry, France
Domenico LeporeDepartment of OphthalmologyCatholic University of the Sacred Heart00168 Rome, Italy
Andrew W. LloydSchool of Pharmacy and Biomolecular
SciencesUniversity of BrightonBrighton, BN2 4GJ, United Kingdom
Patrizia LoriaDepartment of Biophysical Medical and
Odontostomatological Sciences andTechnologies
University of Genova16132 Genoa, Italy
Donald LymanDepartment of Materials Science and
Engineering and Department ofBioengineering
University of UtahSalt Lake City, Utah 84122, United States
Agnese MagnaniDipartimento di Scienze e Tecnologie
Chimiche e dei BiosistemiUniversità degli Studi di Siena53100 Siena, Italy
Walter MarconiDepartment of ChemistryUniversity of Rome “La Sapienza”00185 Rome, Italy
Sabrina MargarucciIstituto di Biochimica delle Proteine ed
EnzimologiaConsiglio Nazionale delle Ricerche0072 Arco Felice, Napoli, Italy
Claudio MigliaresiDepartment of Materials EngineeringUniversity of Trento38050 Trento, Italy
Arturo N. NataliCentre of Mechanics of Biological MaterialsDipartimento di Costruzioni e TrasportiUniversity of Padova35131 Padova, Italy
Paolo A. NettiInstitute of Composite Materials Technology
C.N.R., and C.R.I.B.University of Naples “Federico II”80125 Naples, Italy
Luigi NicolaisInstitute of Composite Materials Technology
C.N.R., and C.R.I.B.University of Naples “Federico II”80125 Naples, Italy
Nicolò Nicoli AldiniExperimental Surgery DepartmentCodivilla-Putti I.O.R. Research Institute40136 Bologna, Italy
Sandro PaciENEA00100 Roma, Italy
Alessandro PegorettiDepartment of Materials EngineeringUniversity of Trento38050 Trento, Italy
Gianfranco PelusoIstituto di Biochimica delle Proteine ed
EnzimologiaConsiglio Nazionale delle Ricerche0072 Arco Felice, Napoli, Italy
x Contributors
Orsolina PetilloIstituto di Biochimica delle Proteine ed
EnzimologiaConsiglio Nazionale delle Ricerche0072 Arco Felice, Napoli, Italy
Maria Rosa PinascoDipartimento di Chimica e Chimica
IndustrialeUniversità degli Studi di Genova16146 Genova, Italy
Antonella PiozziDepartment of ChemistryUniversity of Rome “La Sapienza”00185 Rome, Italy
Erhan PiskinChemical Engineering Department and
Bioengineering DivisionHacettepe University, Beytepe06530, Ankara, Turkey
Arturo PizzoferratoLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
Josep-Anton PlanellCREB (Biomedical Engineering Research
Center)Department of Materials Science and
Metallurgical EngineeringUniversitat Politècnica de Catalunya08028 Barcelona, Spain
Maria Vittoria PrimiceriNotarbartolo & Gervasi SpA00198 Roma, Italy
Marco RadiceInstitute of Histology and EmbryologyFaculty of MedicineUniversity of Padova35121 Padova, Italy
Antonio RavaglioliResearch Institute for Ceramic Technology of
the Italian National Research Council48018 Faenza (Ravenna), Italy
Peter A. RevellDepartment of HistopathologyRoyal Free and University College Medical
SchoolRoyal Free CampusLondon NW3 2PF, United Kingdom
Dante RoncaIstituto di Clinica OrtopedicaUniversità di Napoli80138 Napoli, Italy
Matteo SantinSchool of Pharmacy and Biomolecular
SciencesUniversity of BrightonBrighton, BN2 4GJ, United Kingdom
Lucia SavarinoLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
Luigi ScullicaDepartment of OphthalmologyCatholic University of the Sacred Heart00168 Rome, Italy
Susanna SteaLaboratorio di Fisiopatologia degli Impianti
OrtopediciIstituti Ortopedici Rizzoli40136 Bologna, Italy
Francesco M. VeroneseDepartment of Pharmaceutical SciencesUniversity of Padova35131 Padova, Italy
Libero VitielloDepartment of BiologyUniversity of Padova35121 Padova, Italy
Fabrizio ZucchiCentro Studi Corrosione A. DaccòUniversità di Ferrara44100 Ferrara, Italy
Preface
Progress in medical science has led to an extension of the average humanlifetime, which has brought a rising demand for materials for tissue andorgan replacement. These materials are called biomaterials and the disci-pline involved is called Biomaterials Science,
Biomaterials Science was born to fulfill the demands of patients andphysicians for more efficient as well as new products. These products aredesigned and, first, tested in vitro in research laboratories; they then mustpass through in vivo and clinical experimentation before being introducedinto the market. Integrated Biomaterials Science provides an intriguinginsight into that world, exploring the materials and the technology that hasbrought us new biomaterials. The book covers knowledge in chemistry,engineering, biology, and medicine that has had a significant impact onbiomaterials. In particular, it highlights the way in which modern biologyand medicine is inextricably linked to the other scientific disciplines, allcontributing to the process of discovery and helping us to understand thecomplex world of biomaterials.
Biomaterials Science is multidisciplinary because it needs the supportof many classical disciplines, including Physics, Chemistry, Biology, Engin-eering, and Medicine. Indeed, the special feature of this science is theinterdiscipline among the different areas involved; this means that theremust be perfect integration among the several disciplines in order to developand advance Biomaterials Science. This is its main characteristic and thegreatest difficulty that a researcher faces when studying or simply tryingto understand Biomaterials Science. None of the disciplines involved inBiomaterials Science can be considered the most important; researchersknow perfectly well that no one discipline takes precedence over another,but that there is only good research and bad research.
Although the chapters of this book can be read independently of oneanother, they are arranged in a logical sequence.
The book starts with the study of properties and characteristics ofmaterials used to produce biomaterials. Before dealing with the use of thesebiomaterials as implants, the nature and characteristics of tissues to bereplaced are explained. The interactions occurring between the material andthe biological environment, and thus the tests necessary to prove their
xi
xii Preface
biocompatibility, are treated starting from the intended applications. Somechapters deal with tissue engineering and gene therapy, too. We have alsoincluded aspects less often covered in other biomaterials books, such aspatents and regulations as well as standards on biomaterials, with a viewtoward covering interactions with the industrial world and its needs.
One huge area that we have been unable to include is physicochemicalcharacterization. This subject is so large that it would easily fill a volumeon its own. We do, of course, fully recognize that analytical techniquesdesigned to solve the structures, both in the bulk and on the surface ofbiomaterials, have revolutionized research in biomaterials science, but thetechniques utilized are extremely sophisticated and continuously beingupgraded, so there is a risk that they will be obsolete by the time the bookis published.
This book is a good guide to understanding the subject. Admittedly,there are still large areas of ignorance in biomaterials and many facts thatcannot yet be explained. However, these unsolved problems provide muchof the excitement, and we have tried to point them out in a way that willstimulate readers to join in the enterprise of discovery.
While previous books have supplied extensive information on allsubjects concerning biomaterials, this one is not just informative but isdesigned to provide all the researchers involved in the biomaterials fieldwith an opportunity to probe further: researchers using biomaterials andstudying their properties as well as those involved in their industrialproduction. The book will be extremely useful for students of biomaterialscourses and can be used as a textbook.
Rolando Barbucci
Contents
1. Biological MaterialsYoshito Ikada
1.1.1.2.
1.3.
1.4.
IntroductionFundamentals of Biological Materials1.2.1.1.2.2.1.2.3.1.2.4.1.2.5.
PolypeptidesPolysaccharidesPolyestersInorganic MaterialsComposites
Medical Application of Biological Materials1.3.1.1.3.2.1.3.3.1.3.4.
General SurgeryReplacement of Diseased TissuesDrug Delivery Systems (DDS)Tissue Engineering
ConclusionsReferences
122
511121214141619202222
2. Structure and Properties of Polymeric MaterialsWalter Marconi and Antonella Piozzi
2.1.2.2.
2.3.
2.4.
IntroductionPolymers2.2.1.2.2.2.2.2.3.2.2.4.2.2.5.2.2.6.
General PropertiesSynthesisMolecular WeightIsomerismCrystallinityMechanical Properties
Polymers in Medicine2.3.1.2.3.2.2.3.3.
Synthetic PolymersBiodegradable and Bioresorbable PolymersPolymers for Extracorporeal Enzymatic Detoxification
Requirements and Evaluation of Polymeric Materials2.4.1. Bulk and Surface Properties
2527272930323335363740414343
xiii
xiv Contents
2.4.2.2.4.3.2.4.4.
Chemical ModificationsProduction of Polymeric MaterialsBiological Interaction of Polymer Materials
References
50566366
3. Fundamentals of Polymeric Composite MaterialsClaudio Migliaresi and Alessandro Pegoretti
3.1.3.2.
3.3.
3.4.3.5.3.6.
3.7.
3.8.3.9.
IntroductionFiber Reinforcements3.2.1.3.2.2.3.2.3.
Inorganic FibersCarbon (Graphite) FibersPolymeric Fibers
Matrix Resins3.3.1.3.3.2.
Thermoset MatricesThermoplastic Matrices
Fiber/Matrix AdhesionVolume and Weight FractionsMechanics of Continuous-Fiber-Reinforced Composites3.6.1.3.6.2.3.6.3.
Elastic Properties of a Unidirectional LaminaElastic Properties of a LaminateFailure of a Unidirectional Lamina
Mechanics of Discontinuous-Fiber-Reinforced Composites3.7.1.3.7.2.3.7.3.
Fiber/Matrix Stress TransferElastic Properties of Discontinuous-Fiber CompositesUltimate Properties of Discontinuous-Fiber Composites
Mechanics of Particulate CompositesManufacture of Composites3.9.1.3.9.2.
Manufacture of Thermosetting Polymer CompositesManufacture of Thermoplastic Polymer Composites
References
69717273767879818487888894979999
101105106108108113114
4. Biodegradable PolymersLuca Fambri, Claudio Migliaresi, Kernal Kesenci, and Erhan Piskin
4.1.4.2.4.3.4.4.4.5.
4.6.
IntroductionDefinitionMechanismsProperties and ApplicationsNatural Polymers4.5.1.4.5.2.4.5.3.
Polysaccharide-Based PolymersProtein-Based PolymersMicrobial Polyesters
Synthetic Polymers4.6.1. Aliphatic Polyesters
119120121126129129137143145145
Contents xv
4.6.2.4.6.3.4.6.4.4.6.5.4.6.6.4.6.7.4.6.8.4.6.9.
Poly(ester-amides)PolyorthoestersPolyanhydridesPoly(alkyl 2-cyanoacrylate)Polyimino CarbonatesPolyphosphazenesPolyethyleneterephthalatePolyamides
4.6.10. Polyurethanes4.7. Factors Affecting the Degradation of Polymeric MaterialsReferences
150152154155156157159161163165170
5. Bioceramics and Biological GlassesA. Krajewski and A. Ravaglioli
5.1.
5.2.5.3.
5.4.
The Structure of Ceramics from Synthesis to Processing5.1.1.5.1.2.5.1.3.5.1.4.
CeramicsThe Outstanding Properties of CeramicsThe Drawbacks of CeramicsThe Structural Properties of Ceramics andTheir Possibilities
5.1.5.5.1.6.5.1.7.
Processing of CeramicsThe Thermal ProcessSintering
Design and Duration of Ceramic Devices under LoadCeramics for Surgical Implants5.3.1.5.3.2.5.3.3.5.3.4.5.3.5.
Inert BioceramicsBioactive CeramicsCeramic and Polymeric CarbonsBiological GlassesCoatings
A Survey on the Adhesion of Ceramics to Bone TissueReferences
189190191192
193200202202207208209217240244249252252
6. Metallic MaterialsAlberto Cigada, Roberto Chiesa, Maria Rosa Pinasco,and Kunihiro Hisatsune
6.1.6.2.
The Crystalline Structure of Metallic MaterialsLattice Defects6.2.1.6.2.2.6.2.3.6.2.4.
Point Defects and Solid State DiffusionLinear Defects and Plastic DeformationSurface Defects and Grain BoundariesEffect of Plastic Deformation Temperature on Grain Size
255256257257260261
xvi Contents
6.3.
6.4.
6.5.
6.6.
6.7.
6.8.
Structure of Metallic Alloys6.3.1.6.3.2.6.3.3.6.3.4.
Interstitial Solid SolutionsSubstitutional Solid SolutionsIntermetallic PhasesPresence of More Phases
Phase Diagrams6.4.1.6.4.2.6.4.3.6.4.4.6.4.5.6.4.6.6.4.7.6.4.8.6.4.9.
PhaseVariance and Phase RuleGraphic Representation of Binary Phase DiagramsPresence of One PhasePresence of Two Phases and the Lever RulePresence of Three PhasesIron–Carbon Phase DiagramsIron–Nickel and Iron-Chromium DiagramsTitanium–Aluminum and Titanium–Vanadium Diagrams
6.4.10. Other Phase DiagramsThermal Treatments6.5.1.6.5.2.6.5.3.6.5.4.
Full AnnealingNormalizationQuenchingTempering
Strengthening of Metals6.6.1.6.6.2.6.6.3.6.6.4.6.6.5.
Strengthening by AlloyingStrengthening by Work HardeningStrengthening by Addition of OligoelementsStrengthening by Thermal TreatmentsStrengthening by Order–Disorder Transformations
Working Technologies6.7.1.6.7.2.6.7.3.6.7.4.6.7.5.6.7.6.
Hot or Cold Plastic DeformationMoldingPowder MetallurgyTool MachiningBondingSurface Finishing
Main Metallic Materials Used as Biomaterials6.8.1.6.8.2.6.8.3.6.8.4.
Austenitic Stainless SteelCobalt AlloysTitanium and Titanium AlloysPrecious Metal Alloys
262262262263263263263264264265266267268269269271272276277277277277278278278279279280281285287288288289289290291292294
7. Degradation Processes on Metallic SurfacesEmma Angelini, Angelo Caputo, and Fabrizio Zucchi
7.1.7.2.
IntroductionThe Biological Environment
297297
Contents xvii
7.3.
7.4.
7.5.
Metallic Corrosion7.3.1.7.3.2.7.3.3.7.3.4.
Dry CorrosionWet CorrosionKineticsInfluence of the Biological Environment
Corrosion Forms7.4.1.7.4.2.7.4.3.7.4.4.7.4.5.
Generalized CorrosionLocalized CorrosionGalvanic CorrosionSelective CorrosionWear Corrosion
Corrosion PreventionReferences
298298299303308308309309316320320320323
8. Characterization of BiomaterialsDonald Lyman
8.1.8.2.8.3.
8.4.
Requirements of Biomedical CharacterizationStructure of MaterialsThe Nature of Surface Dynamics and Surface Analysis8.3.1.8.3.2.
Metal and Ceramic SurfacesPolymer Surfaces
Organization of Polymer Surfaces8.4.1.8.4.2.
Anisotropy of Polymer SurfacesMicrophase Heterogeneous Surfaces
References
325327328328329330331332336
9. TissuesLuigi Ambrosio, Paolo A. Netti, and Peter A. Revell
9.1.9.2.9.3.
IntroductionSoft TissuesHard Tissues
References
339340342345
10. Soft TissueLuigi Ambrosio, Paolo A. Netti, and Luigi Nicolais
10.1.
10.2.
Structure–Property Relationship of Soft Tissue10.1.1.10.1.2.10.1.3.
IntroductionMechanical PropertiesTransport Properties
Skin
347347349352353
xviii Contents
10.3.
10.2.1.10.2.2.
Composition and StructureMechanical Properties
Tendons and Ligaments10.3.1.10.3.2.
Composition and StructureMechanical Properties
References
354356357358359363
11. The EyeDomenico Lepore, Luigi Ambrosio, Roberto De Santis,Luigi Nicolais, and Luigi Scullica
11.1.11.2.11.3.11.4.
IntroductionThe CorneaThe ScleraThe Vitreous
References
367368373375379
12. Articular CartilagePaolo A. Netti and Luigi Ambrosio
12.1.12.2.
IntroductionComposition and Structure12.2.1.12.2.2.
CompositionStructure
12.3. Mechanical Properties12.3.1.12.3.2.12.3.3.12.3.4.12.3.5.12.3.6.12.3.7.
Static PropertiesTime-Dependent PropertiesViscoelastic Shear PropertiesViscoelastic Properties in CompressionHydraulic Conductivity of CartilageCompressive Behavior of Articular CartilageConfined Compression
12.4.12.5.
Electromechanical TransductionRemodeling and Repair
References
3813823823 8 3386386388388389390391393394396398
13. The Mechanical and Material Properties of the Healthyand Degenerated Intervertebral DiscRon Alkalay
13.1.13.2.
IntroductionAnatomy13.2.1. Nucleus Pulposus
403404404
Contents xix
13.2.2.13.2.3.
Annulus FibrosusEnd Plate
13.3. Material Properties of the Structures of the Disc13.3.1.13.3.2.13.3.3.
Nucleus PulposusAnnulus FibrosusEnd Plate
13.4.13.5.
Mechanical Behavior of the Intervertebral DiscThe Effect of Degradation on the Mechanical Propertiesof the Disc
13.6.13.7.
Intervertebral Disc ProsthesesSummary
References
405406406406408411411
415416419420
14. Soft Tissue ReplacementMatteo Santin, Luigi Ambrosio, Andrew W. Lloyd,and Stephen P. Denyer
14.1.14.2.
IntroductionCardiovascular Devices14.2.1.14.2.2.14.2.3.
Vascular GraftsVascular StentsSubstitute Heart Valves (SHV)
14.3. Intraocular Devices14.3.1.14.3.2.
Intraocular LensesKeratoprostheses
14.4. Other Applications in Soft Tissue Replacement14.4.1.14.4.2.14.4.3.14.4.4.14.4.5.
Artificial SkinHernia RepairUrological DevicesLigament and Tendon ProsthesesIntervertebral Disc Prostheses
14.5. ConclusionsReferences
425426427431434436437441444444445445446447449450
15. Mechanics of Hard TissuesArturo N. Natali and Richard T. Hart
15.1.15.2.
15.3.
IntroductionExperimental Methods and Results: Determination ofMechanical Properties and Structural Configuration15.2.1.15.2.2.
Mechanical TestingUltrasound Analysis
Mechanics of Bone
459
462462468469
xx Contents
15.3.1.15.3.2.
Material PropertiesStructural Properties
15.4.15.5.
Bone PhysiologyFunctional Adaptation of Bone15.5.1.15.5.2.
Phenomenological ModelsMechanistic Models
15.6.15.7.
Numerical ApproachConclusions
References
469471475476478481482486486
16. Hip Joint ReplacementsGiuseppe Guida and Dante Ronca
16.116.2.16.3.
Introduction to Joint ReplacementsHistoryCemented Prostheses16.3.1.16.3.2.
Femoral StemCotyle
16.4.
16.5.
The Noncemented Prostheses16.4.1.16.4.2.
Femoral StemCotyle
Friction and Wear16.5.1.16.5.2.16.5.3.
Femoral Head MaterialsDimensions of the HeadCotyle Materials
References
491492498498503505505512517518519519520
17. Knee Joint ReplacementsDante Ronca and Giuseppe Guida
17.1.17.2.
IntroductionHistory17.2.1.17.2.2.17.2.3.
Total Knee ArthroplastyHinged Knee ArthroplastyUnicompartmental Knee Arthroplasty
17.3.
17.4.
The Knee: Anatomical, Functional, and StructuralConsiderationsPolyethylene17.4.1.17.4.2.17.4.3.17.4.4.17.4.5.17.4.6.
Contact Stress, Congruency, and ConformityThicknessMetal BackingStrengthDegradationDebris
527529529532534
536537537540541542543544
Contents xxi
17.5.17.6.17.7.17.8.
AlignmentFixationPatellofemoral JointConclusion
References
545546547550550
18. Biomaterial Applications: Elbow ProsthesisLuigi Celli
18.1.18.2.18.3.
IntroductionThe Prosthetic DesignCases in which the Elbow Prosthesis Is Advisable
References
555556558558
19. Biomaterial Applications: Shoulder ProsthesisLuigi Celli
19.1.19.2.19.3.19.4.19.5.19.6.
IntroductionThe Prosthetic DesignThe Prosthetic ImplantationConforming Design of the Articular SurfacesArticular and Periarticular ResistancesThe Active Role of Periarticular Muscles
References
561562563564566566568
20. Acrylic Bone CementsMaria-Pau Ginebra, Francisco-Javier Gil, and Josep-Anton Planell
20.1.20.2.
20.3.
20.4.
IntroductionChemistry of Acrylic Bone Cements20.2.1.20.2.2.20.2.3.
Chemical Composition: Powder and LiquidChemical Reactions and Setting ProcessMolecular Weight
Mechanical Properties20.3.1.20.3.2.20.3.3.20.3.4.
Strength and Elastic ModulusViscoelastic BehaviorFracture ToughnessFatigue
Factors Affecting the Microstructure and theMicrostructure–Mechanical Properties Relationship20.4.1. Porosity
569570570571574574575575576576
578579
xxii Contents
20.4.2.20.4.3.
In Vivo EnvironmentAdditives
20.5.20.6.
Biological PropertiesModification of Acrylic Bone Cements
References
579580582582584
21. Mechanical Properties of Tooth StructuresRoberto De Santis, Luigi Ambrosio, and Luigi Nicolais
21.1.21.2.
IntroductionMechanical Properties21.2.1.21.2.2.21.2.3.
Static Mechanical PropertiesHardnessFracture Toughness
References
589592592595595597
22. Dental Materials and ImplantsMaria Rosa Pinasco, Arturo Natali, Patrizia Loria, Marc Bolla,and Franck J. Hagege
22.1.22.2.22.3.
22.4.22.5.
22.6.22.7.
22.8.
IntroductionStomatognatic Apparatus: Some ConsiderationsDental Materials for Hard and Plastic RestorativeTreatment22.3.1.22.3.2.
Tooth Restoration: Filling, Inlay, and OnlayRestorative Materials: Metals and Alloys,Composite Resins, Glass Ionomers
Materials for Complex ReconstructionsProsthetic Therapy Materials22.5.1.22.5.2.22.5.3.
Fixed Prosthesis MaterialsMoving Partial or Total Prosthesis MaterialsPrecious and Nonprecious Alloys for DentalProstheses
Dental Implant Materials: A Few ConsiderationsBiomaterials for Surgical Reconstitution22.7.1.22.7.2.22.7.3.22.7.4.
Periodontal RegenerationGoal of Osseous GraftingFactors Influencing Graft SuccessRegenerative Materials
Dental Implants and Biomechanics22.8.1.22.8.2.22.8.3.
IntroductionTissue MechanicsImplant Mechanics and Loading
601602
609609
610621622623624
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Contents xxiii
22.8.4. Numerical Formulation of Implant–Tissue InteractionPhenomena
References643647
23. Materials/Biological Environment InteractionsOrsolina Petillo, Alfonso Barbarisi, Sabrina Margarucci,Alfredo De Rosa, and Gianfranco Peluso
23.1.23.2.23.3.23.4.
23.5.
IntroductionCell–Extracellular Matrix InteractionsGrowth Factors–Extracellular Matrix InteractionsExtracellular/Biomaterial Interaction23.4.1.
23.4.2.
23.4.3.
Regulation of Tissue Fibrosis, as an IntegratedCellular Response to BiomaterialFibroblast Cell Activation—a Highly OrchestratedReaction to Biomaterial ImplantationMechano/Transduction by Biomaterials andECM Remodeling
Future PerspectivesReferences
655656658659
659
660
663665666
24. Protein Adsorption and Cellular/Tissue InteractionsAgnese Magnani, Gianfranco Peluso, Sabrina Margarucci,and Krishnan K. Chittur
24.1.24.2.
24.3.
IntroductionProtein Adsorption24.2.1.24.2.2.24.2.3.24.2.4.24.2.5.
What Are Proteins?Protein Structure in Solution and on SurfacesMeasurement of Protein on SurfacesProtein Adsorption to Surfaces: PrinciplesImportance of Protein Adsorption
Cells/Tissue Interactions24.3.1.24.3.2.
The Wound Healing ProcessIn Vivo Models
References
669670670670671674677678678682685
25. Inflammatory Response to Polymeric MaterialsDenis Labarre and Marie-Paule Carreno
25.1.25.2.
IntroductionPolymeric Materials in Contact with Living Tissues
691692
xxiv Contents
25.2.1.25.2.2.
SpecificationsPolymeric Materials
25.3.
25.4.
25.5.
Characteristics of the Materials Involved in the InflammatoryResponse25.3.1.25.3.2.
Size, Surface Area, and Surface MorphologyPhysicochemical Parameters
Assessing the Inflammatory Response to Materials25.4.1.25.4.2.
Materials in Close Contact with BloodMaterials in Contact with Other Tissues
ConclusionAppendix: Abbreviations Used in this ChapterReferences
692695
696697698705706713719723725
26. Inflammatory Response to Metals and CeramicsArturo Pizzoferrato, Elisabetta Cenni, Gabriela Ciapetti,Donatella Granchi, Lucia Savarino, and Susanna Stea
26.1.26.2.
26.3.
26.4.26.5.26.6.
IntroductionMaterials Degradation and Inflammation26.2.1.26.2.2.
Metals and AlloysCeramics
Acute Inflammatory Response26.3.1.26.3.2.26.3.3.26.3.4.26.3.5.
Mediators of the Inflammatory ReactionLeukocyte ExudationCells of the Inflammatory Acute ReactionChemotaxisPhagocytosis
Chronic InflammationToxicity of Biomaterials and InflammationSpecific Immune Response26.6.1.26.6.2.
26.6.3.
Immunogenicity of Metals and CeramicsInteraction between Biomaterials and theImmune SystemMethods for Testing the Immune Specific Response
References
735735736738741742751753755757760767770771
773776780
27. Biocompatibility and Biological TestsAntonietta M. Gatti and Jonathan C. Knowles
27.1.27.2.27.3.
DefinitionBiocompatibility Tests and Their RulesBiological Tests27.3.1.27.3.2.
CytotoxicityGenotoxicity
793795796796802
Contents xxv
27.3.3.27.3.4.27.3.5.27.3.6.27.3.7.27.3.8.27.3.9.
CarcinogenicityReproductive ToxicityIrritation and SensitizationLocal Effect after ImplantationSystemic ToxicityHemocompatibilityDegradation
27.4. Biofunctionality TestsReferences
802803803803804807807810812
28. Infection and SterilizationRoberto Giardino and Nicolò Nicoli Aldini
28.1.
28.2.
Infection28.1.1.28.1.2.28.1.3.28.1.4.
Tissue Reactivity to the ImplantThe Neutrophil ImpairmentThe Protection of the MicroorganismsBacterial Adherence
Sterilization28.2.1.28.2.2.28.2.3.28.2.4.
Steam and Dry HeatEthylene Oxide and Other Chemical AgentsIrradiationElectron (E-Beam) Radiation
References
815816816816817822824824825827829
29. Drug Delivery SystemsFrancesco M. Veronese and Paolo Caliceti
29.1.29.2.
29.3.29.4.
29.5.
IntroductionControlled or Programmable Drug Release versus Slowor Sustained ReleaseBiodegradable and Nonbiodegradable PolymersPolymers for Controlled Release Applications29.4.1.29.4.2.29.4.3.29.4.4.29.4.5.29.4.6.29.4.7.29.4.8.
PolysiloxanesPolyphosphazenesLactic/Glycolic Acid Polymers
PolyanhydridesPolyalkyl AcrylatesPolyacrylate HydrogelsOther Polymers for Controlled Release
Novel Drug Delivery System Preparations29.5.1.29.5.2.
Monolithic MatricesMicrospheres and Nanospheres
833
834836837837839840842844845846848849850851
xxvi Contents
29.5.3. Microcapsules and Nanocapsules29.6.
29.7.
29.8.
29.9.
Internally or Externally Controlled Drug Delivery Systems29.6.1.29.6.2.29.6.3.
Device Erosion Controlled by pHSelf-Modulated DevicesExternally Triggered Devices
Transdermal Therapeutic Delivery Systems29.7.1.29.7.2.29.7.3.
Monolithic DevicesReservoir DevicesSkin Permeability Enhancers
Mechanisms of Drug Release29.8.1.29.8.2.29.8.3.29.8.4.
Undegradable and Unswellable DevicesSwellable and Undegradable MatricesReservoir SystemsBiodegradable Matrices
Overviews of Problems Involving Long-Term Contactbetween Tissues and Drug Delivery Systems
References
852853853855857859860861862864865867868869
870872
30. Gene Delivery as a New Therapeutic ApproachLibero Vitiello and Francesco M. Veronese
30.1.30.2.30.3.30.4.
30.5.
IntroductionDifferent Kinds of Therapeutic Nucleic AcidsViral VectorsSynthetic Vectors30.4.1.30.4.2.30.4.3.
PolyplexesLipoplexesLipopolyplexes
Clinical Applications of Gene TransferReferences
875876877877877879881881882
31. Tissue EngineeringGiovanni Abatangelo, Paola Brun, Marco Radice, Roberta Cortiro,and Marcus K. H. Auth
31.1.31.2.
IntroductionCell Culture and In Vitro Tissue Development31.2.1.31.2.2.31.2.3.31.2.4.
31.2.5.
ECM CompositionECM ReceptorsSignal TransductionTesting Biomaterials and New Strategies forIn Vitro Tissue CultureAssociation of Gene Therapy to Tissue Engineering
885888889892894
895897
Contents xxvii
31.3.
31.4.
31.5.
31.6.
Artificial Skin31.3.1.31.3.2.31.3.3.
EpidermisDermisConclusions
Artificial Cartilage31.4.1.31.4.2.31.4.3.31.4.4.31.4.5.31.4.6.
Properties of Normal and Injured CartilageChondrocyte Cultures In VitroIn Vitro and In Vivo Studies: Cell TherapyCartilage-like Tissue ConstructsMesenchymal Stem CellsConclusions
Artificial Bone31.5.1.31.5.2.31.5.3.31.5.4.31.5.5.
Basic Histology and Physiology of BoneAcellular Approaches for Tissue Engineering of BoneCellular Approaches for Tissue Engineering of BoneTissue Engineered Products: Clinical ConsiderationsSummary
Glandular Parenchyma: The Liver31.6.1.31.6.2.31.6.3.31.6.4.31.6.5.31.6.6.31.6.7.
IntroductionAnatomyLiver MicroarchitectureParenchymal and Nonparenchymal Liver CellsExtracellular MatrixFactors Affecting Liver Cell FunctionPerspectives
References
900901902907907908909910911914916916917918920923924925925926926927927928936936
32. Assist DevicesGerardo Catapano
32.1.32.2.32.3.
32.4.
IntroductionBiomaterials Used in Extracorporeal Blood ProcessingArtificial Devices32.3.1.32.3.2.32.3.3.32.3.4.32.3.5.32.3.6.32.3.7.32.3.8.32.3.9.
Membranes and Their PropertiesTherapeutic Membrane ProcessesMaterials in Artificial DevicesMembrane Preparation TechniquesMembrane MaterialsBiocompatibility IssuesActivation of Blood Coagulation (Thrombogenicity)Complement ActivationCell Activation
Bioartificial Devices32.4.1. Proposed Bioartificial Devices
947949950951956960961964968969971973976976
xxviii Contents
32.4.2.32.4.3.32.4.4.32.4.5.
Materials in Bioartificial DevicesMatrices and ScaffoldsImmunoisolation MaterialsBiocompatibility Issues
Suggested ReadingNomenclature
980981982983983984
33. Standards on BiomaterialsMaria Vittoria Primiceri and Sandro Paci
33.1.
33.2.33.3.
Introduction33.1.1.33.1.2.33.1.3.
The Need for StandardsNational, EN, and ISO StandardsStandard of Quality System
ISO Standards and OverviewEuropean System33.3.1.33.3.2.33.3.3.33.3.4.
EC Directive on Medical DevicesConformity Assessment and CE MarkProcedure to Obtain CEE MarkingAttuned Technical Standards
Bibliography
985985986987989992992994999
10021002
34. Biomaterials and PatentsMaria Vittoria Primiceri
34.1.
34.2.34.3.
Introduction34.1.1.34.1.2.34.1.3.34.1.4.
Historical OverviewThe European Patent ConventionThe Patent Cooperation TreatyThe Patent Application—General Remarksand Patentability Criteria
Patentable InventionsPatentability of Biomaterials
Bibliography
1003100310061007
1009100910121013
Index 1015