Tissue engineering and artificial organs PDF
Preview Tissue engineering and artificial organs
The Biomedical Engineering Handbook Third Edition Tissue Engineering and Artificial Organs © 2006 by Taylor & Francis Group, LLC The Electrical Engineering Handbook Series Series Editor Richard C. Dorf University of California, Davis Titles Included in the Series The Handbook of Ad Hoc Wireless Networks, Mohammad Ilyas The Avionics Handbook, Cary R. Spitzer The Biomedical Engineering Handbook, Third Edition, Joseph D. Bronzino The Circuits and Filters Handbook, Second Edition, Wai-Kai Chen The Communications Handbook, Second Edition, Jerry Gibson The Computer Engineering Handbook, Vojin G. Oklobdzija The Control Handbook, William S. Levine The CRC Handbook of Engineering Tables, Richard C. Dorf The Digital Signal Processing Handbook, Vijay K. Madisetti and Douglas Williams The Electrical Engineering Handbook, Third Edition, Richard C. Dorf The Electric Power Engineering Handbook, Leo L. Grigsby The Electronics Handbook, Second Edition, Jerry C. Whitaker The Engineering Handbook, Third Edition, Richard C. Dorf The Handbook of Formulas and Tables for Signal Processing, Alexander D. Poularikas The Handbook of Nanoscience, Engineering, and Technology, William A. Goddard, III, Donald W. Brenner, Sergey E. Lyshevski, and Gerald J. Iafrate The Handbook of Optical Communication Networks, Mohammad Ilyas and Hussein T. Mouftah The Industrial Electronics Handbook, J. David Irwin The Measurement, Instrumentation, and Sensors Handbook, John G. Webster The Mechanical Systems Design Handbook, Osita D.I. Nwokah and Yidirim Hurmuzlu The Mechatronics Handbook, Robert H. Bishop The Mobile Communications Handbook, Second Edition, Jerry D. Gibson The Ocean Engineering Handbook, Ferial El-Hawary The RF and Microwave Handbook, Mike Golio The Technology Management Handbook, Richard C. Dorf The Transforms and Applications Handbook, Second Edition, Alexander D. Poularikas The VLSI Handbook, Wai-Kai Chen © 2006 by Taylor & Francis Group, LLC The Biomedical Engineering Handbook Third Edition Edited by Joseph D. Bronzino Biomedical Engineering Fundamentals Medical Devices and Systems Tissue Engineering and Artificial Organs © 2006 by Taylor & Francis Group, LLC The Biomedical Engineering Handbook Third Edition Tissue Engineering and Artificial Organs Edited by Joseph D. Bronzino Trinity College Hartford, Connecticut, U.S.A. Boca Raton London New York A CRC title, part of the Taylor & Francis imprint, a member of the Taylor & Francis Group, the academic division of T&F Informa plc. © 2006 by Taylor & Francis Group, LLC Published in 2006 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2006 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-2123-9 (Hardcover) International Standard Book Number-13: 978-0-8493-2123-8 (Hardcover) Library of Congress Card Number 2005044776 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Tissue engineering and artificial organs / edited by Joseph D. Bronzino. p. cm. -- (The electrical engineering handbook series) Includes bibliographical references and index. ISBN 0-8493-2123-9 (alk. paper) 1. Tissue engineering. 2. Artificial organs. I. Bronzino, Joseph D., 1937- II. Title. III. Series. R857.T55T547 2006 612.028--dc22 2005044776 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com Taylor & Francis Group and the CRC Press Web site at is the Academic Division of Informa plc. http://www.crcpress.com © 2006 by Taylor & Francis Group, LLC Introduction and Preface During the past five years since the publication of the Second Edition — a two-volume set — of the BiomedicalEngineeringHandbook,thefieldofbiomedicalengineeringhascontinuedtoevolveandexpand. Asaresult, thisThirdEditionconsistsof athree-volumeset, whichhasbeensignificantlymodifiedto reflectthestate-of-the-fieldknowledgeandapplicationsinthisimportantdiscipline. Morespecifically, thisThirdEditioncontainsanumberofcompletelynewsections,including: • MolecularBiology • Bionanotechnology • Bioinformatics • Neuroengineering • InfraredImaging aswellasanewsectiononethics. Inaddition,allofthesectionsthathaveappearedinthefirstandsecondeditionshavebeensignificantly revised. Therefore, this Third Edition presents an excellent summary of the status of knowledge and activitiesofbiomedicalengineersinthebeginningofthe21stcentury. Assuch,itcanserveasanexcellentreferenceforindividualsinterestednotonlyinareviewoffunda- mentalphysiology,butalsoinquicklybeingbroughtuptospeedincertainareasofbiomedicalengineering research.Itcanserveasanexcellenttextbookforstudentsinareaswheretraditionaltextbookshavenot yetbeendevelopedandasanexcellentreviewofthemajorareasofactivityineachbiomedicalengineer- ingsubdiscipline,suchasbiomechanics,biomaterials,bioinstrumentation,medicalimaging,etc.Finally, itcanserveasthe“bible”forpracticingbiomedicalengineeringprofessionalsbycoveringsuchtopicsasa historicalperspectiveofmedicaltechnology,theroleofprofessionalsocieties,theethicalissuesassociated withmedicaltechnology,andtheFDAprocess. Biomedical engineering is now an important vital interdisciplinary field. Biomedical engineers are involvedinvirtuallyallaspectsofdevelopingnewmedicaltechnology.Theyareinvolvedinthedesign, development,andutilizationofmaterials,devices(suchaspacemakers,lithotripsy,etc.)andtechniques (suchassignalprocessing,artificialintelligence,etc.)forclinicalresearchanduse;andserveasmembers of the health care delivery team (clinical engineering, medical informatics, rehabilitation engineering, etc.)seekingnewsolutionsfordifficulthealthcareproblemsconfrontingoursociety.Tomeettheneeds ofthisdiversebodyofbiomedicalengineers,thishandbookprovidesacentralcoreofknowledgeinthose fieldsencompassedbythediscipline.However,beforepresentingthisdetailedinformation,itisimportant toprovideasenseof theevolutionof themodernhealthcaresystemandidentifythediverseactivities biomedicalengineersperformtoassistinthediagnosisandtreatmentofpatients. Evolution of the Modern Health Care System Before 1900, medicine had little to offer the average citizen, since its resources consisted mainly of the physician, his education, and his “little black bag.” In general, physicians seemed to be in short © 2006 by Taylor & Francis Group, LLC supply, but the shortage had rather different causes than the current crisis in the availability of health careprofessionals.Althoughthecostsofobtainingmedicaltrainingwererelativelylow,thedemandfor doctors’servicesalsowasverysmall,sincemanyoftheservicesprovidedbythephysicianalsocouldbe obtainedfromexperiencedamateursinthecommunity. Thehomewastypicallythesitefortreatment andrecuperation,andrelativesandneighborsconstitutedanableandwillingnursingstaff.Babieswere delivered by midwives, and those illnesses not cured by home remedies were left to run their natural, albeitfrequentlyfatal,course.Thecontrastwithcontemporaryhealthcarepractices,inwhichspecialized physicians and nurses located within the hospital provide critical diagnostic and treatment services, is dramatic. The changes that have occurred within medical science originated in the rapid developments that took place in the applied sciences (chemistry, physics, engineering, microbiology, physiology, phar- macology, etc.) at the turn of the century. This process of development was characterized by intense interdisciplinarycross-fertilization,whichprovidedanenvironmentinwhichmedicalresearchwasable totakegiantstridesindevelopingtechniquesforthediagnosisandtreatmentof disease. Forexample, in 1903, Willem Einthoven, a Dutch physiologist, devised the first electrocardiograph to measure the electrical activity of the heart. In applying discoveries in the physical sciences to the analysis of the biologic process, he initiated a new age in both cardiovascular medicine and electrical measurement techniques. Newdiscoveriesinmedicalsciencesfollowedoneanotherlikeintermediatesinachainreaction.How- ever, the most significant innovation for clinical medicine was the development of x-rays. These“new kinds of rays,” as their discoverer W.K. Roentgen described them in 1895, opened the“inner man”to medicalinspection.Initially,x-rayswereusedtodiagnosebonefracturesanddislocations,andinthepro- cess,x-raymachinesbecamecommonplaceinmosturbanhospitals.Separatedepartmentsofradiology wereestablished,andtheirinfluencespreadtootherdepartmentsthroughoutthehospital.Bythe1930s, x-rayvisualizationofpracticallyallorgansystemsofthebodyhadbeenmadepossiblethroughtheuseof bariumsaltsandawidevarietyofradiopaquematerials. X-raytechnologygavephysiciansapowerfultoolthat,forthefirsttime,permittedaccuratediagnosis of a wide variety of diseases and injuries. Moreover, since x-ray machines were too cumbersome and expensive for local doctors and clinics, they had to be placed in health care centers or hospitals. Once there,x-raytechnologyessentiallytriggeredthetransformationofthehospitalfromapassivereceptacle forthesicktoanactivecurativeinstitutionforallmembersofsociety. Foreconomicreasons,thecentralizationofhealthcareservicesbecameessentialbecauseofmanyother importanttechnologicalinnovationsappearingonthemedicalscene.However,hospitalsremainedinsti- tutionstodread,anditwasnotuntiltheintroductionofsulfanilamideinthemid-1930sandpenicillinin theearly1940sthatthemaindangerofhospitalization,thatis,cross-infectionamongpatients,wassigni- ficantlyreduced.Withthesenewdrugsintheirarsenals,surgeonswereabletoperformtheiroperations withoutprohibitivemorbidityandmortalityduetoinfection. Furthermore, eventhoughthedifferent bloodgroupsandtheirincompatibilitywerediscoveredin1900andsodiumcitratewasusedin1913to prevent clotting, full development of blood banks was not practical until the 1930s, when technology providedadequaterefrigeration.Untilthattime,“fresh”donorswerebledandthebloodtransfusedwhile itwasstillwarm. Oncethesesurgicalsuiteswereestablished,theemploymentofspecificallydesignedpiecesofmedical technologyassistedinfurtheradvancingthedevelopmentofcomplexsurgicalprocedures.Forexample, theDrinkerrespiratorwasintroducedin1927andthefirstheart–lungbypasswasdonein1939.Bythe 1940s,medicalproceduresheavilydependentonmedicaltechnology,suchascardiaccatheterizationand angiography(theuseof acannulathreadedthroughanarmveinandintotheheartwiththeinjection of radiopaque dye) for the x-ray visualization of congenital and acquired heart disease (mainly valve disordersduetorheumaticfever)becamepossible, andaneweraof cardiacandvascularsurgerywas established. Following World War II, technological advances were spurred on by efforts to develop superior weaponsystemsandestablishhabitatsinspaceandontheoceanfloor.Asaby-productoftheseefforts, © 2006 by Taylor & Francis Group, LLC thedevelopmentof medicaldevicesacceleratedandthemedicalprofessionbenefitedgreatlyfromthis rapidsurgeoftechnologicalfinds.Considerthefollowingexamples: 1. Advancesinsolid-stateelectronicsmadeitpossibletomapthesubtlebehaviorofthefundamental unitofthecentralnervoussystem—theneuron—aswellastomonitorthevariousphysiological parameters,suchastheelectrocardiogram,ofpatientsinintensivecareunits. 2. Newprostheticdevicesbecameagoalofengineersinvolvedinprovidingthedisabledwithtools toimprovetheirqualityoflife. 3. Nuclear medicine — an outgrowth of the atomic age — emerged as a powerful and effective approachindetectingandtreatingspecificphysiologicabnormalities. 4. Diagnostic ultrasound based on sonar technology became so widely accepted that ultrasonic studiesarenowpartoftheroutinediagnosticworkupinmanymedicalspecialties. 5. “Spareparts”surgeryalsobecamecommonplace.Technologistswereencouragedtoprovidecar- diacassistdevices,suchasartificialheartvalvesandartificialbloodvessels,andtheartificialheart programwaslaunchedtodevelopareplacementforadefectiveordiseasedhumanheart. 6. Advancesinmaterialshavemadethedevelopmentofdisposablemedicaldevices,suchasneedles andthermometers,aswellasimplantabledrugdeliverysystems,areality. 7. ComputerssimilartothosedevelopedtocontroltheflightplansoftheApollocapsulewereusedto store,process,andcross-checkmedicalrecords,tomonitorpatientstatusinintensivecareunits, andtoprovidesophisticatedstatisticaldiagnosesofpotentialdiseasescorrelatedwithspecificsets ofpatientsymptoms. 8. Developmentofthefirstcomputer-basedmedicalinstrument,thecomputerizedaxialtomography scanner,revolutionizedclinicalapproachestononinvasivediagnosticimagingprocedures,which nowincludemagneticresonanceimagingandpositronemissiontomographyaswell. 9. A wide variety of new cardiovascular technologies including implantable defibrillators and chemicallytreatedstentsweredeveloped. 10. Neuronalpacingsystemswereusedtodetectandpreventepilepticseizures. 11. Artificialorgansandtissuehavebeencreated. 12. Thecompletionofthegenomeprojecthasstimulatedthesearchfornewbiologicalmarkersand personalizedmedicine. Theimpactofthesediscoveriesandmanyothershasbeenprofound.Thehealthcaresystemoftoday consistsof technologicallysophisticatedclinicalstaff operatingprimarilyinmodernhospitalsdesigned to accommodate the new medical technology. This evolutionary process continues, with advances in the physical sciences such as materials and nanotechnology, and in the life sciences such as molecular biology,thegenomeprojectandartificialorgans.Theseadvanceshavealteredandwillcontinuetoalter theverynatureofthehealthcaredeliverysystemitself. Biomedical Engineering: A Definition Bioengineeringisusuallydefinedasabasicresearch-orientedactivitycloselyrelatedtobiotechnologyand geneticengineering,thatis,themodificationofanimalorplantcells,orpartsofcells,toimproveplants oranimalsortodevelopnewmicroorganismsforbeneficialends.Inthefoodindustry,forexample,this has meant the improvement of strains of yeast for fermentation. In agriculture, bioengineers may be concernedwiththeimprovementof cropyieldsbytreatmentof plantswithorganismstoreducefrost damage. It is clear that bioengineers of the future will have a tremendous impact on the qualities of human life. The potential of this specialty is difficult to imagine. Consider the following activities of bioengineers: • Developmentofimprovedspeciesofplantsandanimalsforfoodproduction • Inventionofnewmedicaldiagnostictestsfordiseases • Productionofsyntheticvaccinesfromclonecells © 2006 by Taylor & Francis Group, LLC The world of biomedical engineering Biomechanics Medical & Prosthetic devices biological analysis & artificial organs Biosensors Medical imaging Clinical Biomaterials engineering Biotechnology Medical & bioinformatics Tissue engineering Rehabilitation Neural engineering engineering Physiological Biomedical modeling instrumentation Bionanotechnology FIGURE1 Theworldofbiomedicalengineering. • Bioenvironmental engineering to protect human, animal, and plant life from toxicants and pollutants • Studyofprotein–surfaceinteractions • Modelingofthegrowthkineticsofyeastandhybridomacells • Researchinimmobilizedenzymetechnology • Developmentoftherapeuticproteinsandmonoclonalantibodies Biomedical engineers, on the other hand, apply electrical, mechanical, chemical, optical, and other engineeringprinciplestounderstand,modify,orcontrolbiologic(i.e.,humanandanimal)systems,as wellasdesignandmanufactureproductsthatcanmonitorphysiologicfunctionsandassistinthediagnosis andtreatmentof patients. Whenbiomedicalengineersworkwithinahospitalorclinic, theyaremore properlycalledclinicalengineers. Activities of Biomedical Engineers The breadth of activity of biomedical engineers is now significant. The field has moved from being concernedprimarilywiththedevelopmentof medicalinstrumentsinthe1950sand1960stoincludea morewide-rangingsetofactivities.Asillustratedabove,thefieldofbiomedicalengineeringnowincludes manynewcareerareas(seeFigure1),eachofwhichispresentedinthishandbook.Theseareasinclude: • Application of engineering system analysis (physiologic modeling, simulation, and control) to biologicproblems • Detection,measurement,andmonitoringof physiologicsignals(i.e.,biosensorsandbiomedical instrumentation) • Diagnosticinterpretationviasignal-processingtechniquesofbioelectricdata • Therapeuticandrehabilitationproceduresanddevices(rehabilitationengineering) • Devicesforreplacementoraugmentationofbodilyfunctions(artificialorgans) • Computeranalysisofpatient-relateddataandclinicaldecisionmaking(i.e.,medicalinformatics andartificialintelligence) © 2006 by Taylor & Francis Group, LLC • Medicalimaging,thatis,thegraphicdisplayofanatomicdetailorphysiologicfunction • Thecreationofnewbiologicproducts(i.e.,biotechnologyandtissueengineering) • Thedevelopmentofnewmaterialstobeusedwithinthebody(biomaterials) Typicalpursuitsofbiomedicalengineers,therefore,include: • Researchinnewmaterialsforimplantedartificialorgans • Developmentofnewdiagnosticinstrumentsforbloodanalysis • Computermodelingofthefunctionofthehumanheart • Writingsoftwareforanalysisofmedicalresearchdata • Analysisofmedicaldevicehazardsforsafetyandefficacy • Developmentofnewdiagnosticimagingsystems • Designoftelemetrysystemsforpatientmonitoring • Designofbiomedicalsensorsformeasurementofhumanphysiologicsystemsvariables • Developmentofexpertsystemsfordiagnosisofdisease • Designofclosed-loopcontrolsystemsfordrugadministration • Modelingofthephysiologicalsystemsofthehumanbody • Designofinstrumentationforsportsmedicine • Developmentofnewdentalmaterials • Designofcommunicationaidsforthehandicapped • Studyofpulmonaryfluiddynamics • Studyofthebiomechanicsofthehumanbody • Developmentofmaterialtobeusedasreplacementforhumanskin Biomedicalengineering,then,isaninterdisciplinarybranchofengineeringthatrangesfromtheoretical, nonexperimentalundertakingstostate-of-the-artapplications.Itcanencompassresearch,development, implementation, and operation. Accordingly, like medical practice itself, it is unlikely that any single personcanacquireexpertisethatencompassestheentirefield.Yet,becauseoftheinterdisciplinarynature of this activity, there is considerable interplay and overlapping of interest and effort between them. For example, biomedical engineers engaged in the development of biosensors may interact with those interestedinprostheticdevicestodevelopameanstodetectandusethesamebioelectricsignaltopower aprostheticdevice.Thoseengagedinautomatingtheclinicalchemistrylaboratorymaycollaboratewith thosedevelopingexpertsystemstoassistcliniciansinmakingdecisionsbasedonspecificlaboratorydata. Thepossibilitiesareendless. Perhapsagreaterpotentialbenefitoccurringfromtheuseofbiomedicalengineeringisidentification oftheproblemsandneedsofourpresenthealthcaresystemthatcanbesolvedusingexistingengineering technologyandsystemsmethodology.Consequently,thefieldofbiomedicalengineeringoffershopein thecontinuingbattletoprovidehigh-qualitycareatareasonablecost.Ifproperlydirectedtowardsolving problems related to preventive medical approaches, ambulatory care services, and the like, biomedical engineerscanprovidethetoolsandtechniquestomakeourhealthcaresystemmoreeffectiveandefficient; andintheprocess,improvethequalityoflifeforall. JosephD.Bronzino Editor-in-Chief © 2006 by Taylor & Francis Group, LLC
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