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ENCYCLOPEDIA OF
BIOMEDICAL ENGINEERING
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ENCYCLOPEDIA OF
BIOMEDICAL ENGINEERING
EDITOR IN CHIEF
Roger Narayan
University of North Carolina at Chapel Hill, Chapel Hill,
NC, United States
VOLUME 1
Section Editors
Min Wang
The University of Hong Kong, Pokfulam, Hong Kong
Cato Laurencin
University of Connecticut Health Center, Farmington, CT, United States
Xiaojun Yu
Stevens Institute of Technology, Hoboken, NJ, United States
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EDITORIAL BOARD
EDITOR IN CHIEF
Roger Narayan
University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
SECTION EDITORS
Levi Hargrove
Rehabilitation Institute of Chicago, Chicago, IL, United States
Christian Hellmich
TU Wien, Vienna University of Technology, Vienna, Austria
Sri Krishnan
Ryerson University, Toronto, ON, Canada
Cato Laurencin
University of Connecticut Health Center, Farmington, CT, United States
Diego Mantovani
Laval University, Quebec City, QC, Canada
William Z Rymer
Rehabilitation Institute of Chicago, Chicago, IL, United States
Pankaj Vadgama
Queen Mary University of London, London, United Kingdom
Min Wang
Alexander Wong
University of Waterloo, Waterloo, ON, Canada
Xiaojun Yu
Stevens Institute of Technology, Hoboken, NJ, United States
v
EDITOR IN CHIEF
Roger Narayan
Dr. Roger Narayan is a professor in the Joint Department of Biomedical Engineering at the
University of North Carolina and North Carolina State University. He is an author of over 200
publications as well as several book chapters on processing, characterization, and modeling of bio-
logical and biomedical materials. Dr. Narayan has edited several books, including Biomedical Mate-
rials, Printed Biomaterials, Computer Aided Biomanufacturing, Diamond-Based Materials for Biomedical
Applications, Medical Biosensors for Point of Care (POC) Applications, Monitoring and Evaluation of Bioma-
terials and their Performance In Vivo, Nanobiomaterials: Nanostructured Materials for Biomedical Applica-
tions, and the ASM Handbook on Materials for Medical Devices. He has previously served as chair of the
Functional Materials Division of The Minerals, Metals & Materials Society and is currently chair-elect
of the Bioceramics Division of American Ceramics Society. Dr. Narayan has received several honors
for his research activities, including the North Carolina State University Alcoa Foundation Engi-
neering Research Achievement Award, the North Carolina State University Sigma Xi Faculty
Research Award, the University of North Carolina Jefferson-Pilot Fellowship in Academic Medicine,
the National Science Faculty Early Career Development Award, the Office of Naval Research Young
Investigator Award, the American Ceramic Society Richard M. Fulrath Award, the Royal Academy of Engineering Distinguished Visiting
Fellowship, and TMS Brimacombe Medal. He has served as Fulbright Scholar at the University of Otago, the National Polytechnic Institute
(Mexico City), and the University of Sao Paulo. He has been elected as Fellow of ASM International, the American Association for the
Advancement of Science, the American Ceramic Society, and the American Institute for Medical and Biological Engineering.
vii
SECTION EDITORS
Levi Hargrove
Dr. Hargrove is currently the Director of the Center for Bionic Medicine and of the Neural Engi-
neering for Prosthetic and Orthotics Laboratory at the Shirley Ryan AbilityLab. He is also an
Associate Professor in the Departments of Physical Medicine and Rehabilitation and the
McCormick School of Engineering at Northwestern University.
A major goal of his research is to develop clinically realizable myoelectric control systems
that can be made available to persons with limb loss in the near future. His research addresses
all levels of amputation and has been published in the Journal of the American Medical Associ-
ation and the New England Journal of Medicine, and multiple patents. Key projects include the
development of advanced and adaptive control systems for prosthetic legs, improving control
of robotic hand prostheses, and intramuscular EMG signal processing. In 2012, Dr. Hargrove
cofounded Coapt, a company to transition advanced rehabilitation technologies from the
research laboratory to patients’ homes.
Christian Hellmich
Dr. Christian Hellmich, Full Professor at the Department of Civil Engineering of the Vienna
University of Technology (TU Wien), is the director of the Institute for Mechanics of Materials
and Structures. At TU Wien, he received his engineering, Ph.D., and habilitation degrees (in
1995, 1999, and 2004, respectively). From 2000 to 2002, he was a Max Kade Postdoctoral
Fellow in the Department of Civil and Environmental Engineering at the Massachusetts Insti-
tute of Technology. His work is strongly focused on well-validated material and (micro)struc-
tural models, in terms of theoretical foundations and applications to concrete, soil, rock,
wood, bone, and biomedical implants, up the structural level (tunnels, pipelines, bridges, bio-
logical organs such as the skeleton)dwith complementary experimental activities if necessary.
He has led several projects for the tunnel, railway, and pipeline industries, as well as interna-
tional research activities sponsored by the European Commission, including the coordination
of the mixed industry-academia consortium “BIO-CT-EXPLOIT” at the crossroads of numer-
ical simulation and computer tomography, or the cross-domain COST action NAMABIO inte-
grating engineers, physicists, (stem) cell biologists, and medical doctors across the European
continent and beyond. He has published more than 130 papers in international refereed
scientific journals in the fields of engineering mechanics, materials science, and theoretical biology, more than 20 book chapters,
and more than 120 papers in refereed conference proceedings. Dr. Hellmich has served as the Chairman of both the Properties of
Materials Committee of the Engineering Mechanics Division of the American Society of Civil Engineers (ASCE), and the Porome-
chanics and Biomechanics Committees of the Engineering Mechanics Institute (EMI), as associate editor of the Journal of Engineering
Mechanics (ASCE), and as Coeditor in Chief of the Journal of Nanomechanics and Micromechanics (ASCE). As community service, he
has (co)chaired and/or supported more than 50 international conferences (including chairmanship of the 2013 Biot Conference on
Poromechanics and the 2015 CONCREEP conference; both EMI-ASCE supported), and he has reviewed for 128 different scientific
journals and 15 science foundations. He was awarded the Kardinal Innitzer Science Award of the Archbishopry of Vienna in 2004
(for his habilitation thesis), the Science Award of the State of Lower Austria in 2005 (for his achievements in the micromechanics of
hierarchical composites), and he was the recipient of the 2008 Zienkiewicz Award for Young Scientists in Computational Engi-
neering Sciences, sponsored by the European Community on Computational Methods in Applied Sciences (ECCOMAS). For further
activities in the multiscale poromicromechanics of bone materials, he received one of the highly prestigious ERC Grants of the
ix
x Section Editors
European Research Council in 2010; and he was elected member of the Young Academy of the Austrian Academy of Sciences in
2011. In 2012, he was rewarded the prestigious Walter L. Huber Research Prize of the ASCE, for his contributions to the micropor-
omechanics of hierarchical geomaterials and biomaterials; he was elected Fellow of EMI in 2014 and was corecipient of the 2017
Kajal Mallick Memorial Award of the Institution of Civil Engineers (United Kingdom).
Sri Krishnan
Sridhar (Sri) Krishnan received B.E. degree in Electronics and Communication Engineering
from the College of Engineering, Guindy, Anna University, Chennai, India, in 1993, and
M.Sc. and Ph.D. degrees (with student fellowship from Alberta Heritage Foundation for
Medical Research) in Electrical and Computer Engineering from The University of Calgary,
Calgary, Alberta, Canada, in 1996 and 1999, respectively. Sri Krishnan joined Ryerson Univer-
sity in July 1999 and is currently a Professor in the Department of Electrical and Computer
Engineering. Since July 2011, he is an Associate Dean (Research, Development and External
Partnerships) for the Faculty of Engineering and Architectural Science. He is also the Codi-
rector of the Institute for Biomedical Engineering, Science and Technology (iBEST) and an
affiliate scientist at the Keenan Research Centre in St. Michael’s Hospital, Toronto.
Since January 2002 Sri Krishnan held various administrative leadership positions in the
Department of Electrical and Computer Engineering and the Faculty of Engineering and
Architectural Science. In 2010–2011, Sri Krishnan held Visiting Appointments in University
of Rennes 1 (France), Grenoble Institute of Technology (France) and Indian Institute of Tech-
nology (Madras). Sri Krishnan is a registered professional engineer in the Province of Ontario and is a senior member of IEEE (EMBS
and SP societies). He was the Founding Chair (2005–2015) of IEEE Signal Processing Society, Toronto Section and Region 7 (Can-
ada), and a Founding Member of the IEEE Engineering in Medicine and Biology Society, Toronto Section. He currently serves as
a Technical Committee Member (Biomedical Signal Processing) of IEEE EMBS.
Sri Krishnan held the Canada Research Chair position (2007–2017) in Biomedical Signal Analysis. Sri Krishnan has successfully
supervised/trained 10 postdoc fellows, 10 Ph.D., 30 Masters (thesis), 9 Masters (project), 42 RAs, and 20 Visiting RAs. Sri Krishnan’s
research interests include adaptive signal representations and analysis and their applications in biomedicine, multimedia (audio),
and biometrics. He has published 295 papers in refereed journals and conferences, filed 10 invention disclosures, and has one US
patent. He has presented keynote/plenary/invited talks in more than 35 international conferences and workshops. Sri Krishnan also
serves as a reviewer, committee member, and chair for many international conferences, journals, and granting bodies. Sri Krishnan’s
academic interests include (interdisciplinary) curriculum design, experiential learning, and innovation. Sri Krishnan serves in the
advisory boards of research institutes, innovation centers, incubator zones, and business organizations.
Sri Krishnan is a recipient/awarded Outstanding Canadian Biomedical Engineer Award 2016; Certificate of Appreciation from
PEO York Chapter 2016; Fellow of Canadian Academy of Engineering in 2014; 2014 Exemplary Service Award from IEEE Toronto
Section; 2014 Certificate of Merit from IEEE Signal Processing Society; 2013 Achievement in Innovation Award from Innovate Cal-
gary; 2011 Sarwan Sahota Distinguished Scholar Award; 2011 Certificate of Appreciation from IEEE Signal Processing Society; 2010
Shastri Visiting Professorship; 2010 French Embassy Visiting Researcher; 2008 Ontario Research Innovation Award from Bio-
discovery Toronto; 2007 Canadian Engineers’ Young Engineer Achievement Award from Engineers’ Canada; 2006 New Pioneers
Award in Science and Technology; 2006 South Asian Community Achiever Award; 2006 IEEE Toronto Section Best Chapter Chair
Award; 2005 IEEE AESS Best Chapter Chair Award; 2005 IEEE Certificate of Appreciation from Six Societies; Six Best Research Paper
Awards coauthored with his graduate students in International Conferences; and 2005 FEAS Research Excellence Award.
Cato Laurencin
Cato T. Laurencin, M.D., Ph.D. is the University Professor at UCONN. He is the eighth desig-
nated in UCONN’s history. He is Professor of Chemical Engineering, Professor of Materials
Science and Engineering, and Professor of Biomedical Engineering, and the Van Dusen Distin-
guished Endowed Professor of Orthopaedic Surgery. He directs the Institute for Regenerative
Engineering and the Raymond and Beverly Sackler Center at the University of Connecticut.
Dr. Laurencin earned his B.S.E. degree in Chemical Engineering from Princeton University.
He earned his Ph.D. in Biochemical Engineering/Biotechnology from the Massachusetts Insti-
tute of Technology where he was named a Hugh Hampton Young Fellow. At the same time, he
earned his M.D., Magna Cum Laude from the Harvard Medical School where he received the
Robinson Award for Surgery.
Dr. Laurencin is an expert in biomaterials, nanotechnology, stem cell science, and, the new
field he has pioneered, Regenerative Engineering. He is a fellow of American Institute of Chemical
Section Editors xi
Engineers and was named one of the 100 Engineers of the Modern Era by the AICHE. He received the Percy Julian Medal from National
Organization of Black Chemists and Chemical Engineers, and the Pierre Galletti Award from the American Institute of Medical and
Biological Engineering. He has received the NIH Director’s Pioneer Award and the National Science Foundation Emerging Frontiers
in Research and Innovation Award for his research in Regenerative Engineering.
Dr. Laurencin is an elected member of the National Academy of Engineering, the National Academy of Medicine, the Indian
National Academy of Engineering, the Indian National Academy of Sciences, and the African Academy of Sciences. He is an acade-
mician and foreign member of the Chinese Academy of Engineering.
Dr. Laurencin has two awards named in his honor. The W. Montague Cobb Institute and the National Medical Association estab-
lished the Cato T. Laurencin Lifetime Research Achievement Award, while the Society for Biomaterials established The Cato T. Lau-
rencin, M.D., Ph.D. Travel Fellowship Award.
Dr. Laurencin received the Presidential Faculty Fellow Award from President Bill Clinton and the Presidential Award for Excel-
lence in Science, Mathematics, and Engineering Mentoring from President Barack Obama. He is the recipient of the National Medal
of Technology and Innovation, America’s highest award for technological achievement from President Barack Obama in ceremonies
at the White House.
Diego Mantovani, Ph.D., FBSE.

Prof. Diego Mantovani is the director of Laboratory for Biomaterials and Bioengineering at
Laval University, in Canada, and senior scientist of the Regenerative Medicine Division of
the Quebec University Hospital Research Centre. He received his doctoral degree jointly
from University of Technology of Compiègne, France, and Laval University in 1999 and his
joint Diploma in Engineering from Politecnico di Milano and the University of Technology
of Compiegne, France, in 1993. After an industrial postdoc (1999), he becomes professor
at Laval University School of Science and Engineering in 2000. Since the beginning he estab-
lished is Laboratory at the University Hospital Research Center in Quebec City. Within his
team, researches focus on surface modifications by plasma, thin polymer functional films,
cell–materials interactions, degradable metals, scaffolds, and bioreactors for the replacement
and regeneration of cardiovascular tissue. He has authored more than 260 original articles,
holds 5 patents, and presented more than 185 keynotes, invited and seminar lectures world-
wide. His H-index is 43 (June 2018), and his works were cited more than 7000 times. He was
President of the Canadian Society for Biomaterials (2008–2009), and Executive Cochair of
the World Biomaterials Congress in 2016 in Montreal, Canada. In 2012, he was elected Fellow of the World Biomaterials Science
and Engineering Society. Since 2012, he is the holder of the Canada Research Chair 1 in Biomaterials and Bioengineering for the
Innovation in Surgery. He was member of ad hoc panels at FDA, ISO, and Health Canada and member of a number of funding,
regulatory and scientific committees worldwide. He is Adjunct Professor at Politecnico di Milano and Universita del Piemonte Ori-
entale in Italy, as well as at the Vellore Institute of Technology, in India. He was invited professor in several universities worldwide,
including Campinas, Brasil (2012–2015), Bologna (2015), Bordeaux (2014), Siao Tong West, China (2012), Cergy-Pontoise
(2012), ParisTech (2011), Buenos Aires (2010), Namur, Belgium (2008), Tor Vergata, Italy (2007), Ankara, Turkey (2006), and
others. He is member of the editorial board of five scientific journals in the field and of the advisory board of three medical devices
consortia worldwide.
William Z Rymer
Professor William Z Rymer is Professor of Physical Medicine and Rehabilitation and Physi-
ology at the Rehabilitation Institute of Chicago, Chicago, IL, United States. His focus of
work includes pathophysiology, stroke, spinal cord injury, spinal circuits, biomedical engi-
neering, and neural signal processing.
xii Section Editors
Pankaj Vadgama
Pankaj Vadgama qualified in Degree in Medicine and then in Chemistry at the University of
Newcastle upon Tyne, United Kingdom, with a First Class Honors BSc. He is a chemical
pathologist, becoming a Fellow of the Royal College of Pathology. He completed his Ph.D.
on medical biosensors as an MRC Fellow at Newcastle, and while there, he was made Director
of the Biosensors Group and later appointed as Professor of Clinical Biochemistry at the
University of Manchester, subsequently becoming Research Dean for the Faculty of Medicine.
He was appointed Director of the Interdisciplinary Research Centre in Biomedical Materials at
Queen Mary, University of London and was, until recently, Head of the Department of Clin-
ical Biochemistry, Barts Health NHS Trust. His main interests are variously biosensors,
applied bioelectrochemistry, point-of-care testing, and membrane technology. He has pub-
lished over 200 papers. He is also Fellow of the Royal Society of Medicine, Institute of Physics,
Royal Society of Chemistry, the Institute of Materials Minerals and Mining, and the Royal
Society of Biology. He was given the Foundation Award of the Association of Clinical
Biochemistry and Laboratory Medicine, has been a Sandoz Lecturer of the British Geriatric
Society, and delivered the Latner lecture at the University of Newcastle. He has served on
various UK Research Council grants award committees and is at present member of the Insti-
tute of Materials Minerals and Mining Smart Materials and Nano Committees and the
Biomedical Materials Application Division. He sits on various BSI committees and was Chair of the ISO subpanel on nanomedicine
nomenclature. He sits on various editorial boards and is Editor in Chief of Bioelectrochemistry. He is Deputy Chair of the Council for
the Frontiers of Science based in Uganda directed at research training in East Africa.
Min Wang
Min Wang is a Full Professor at The University of Hong Kong (HKU), and as Programme
Director (2013–2018), he has led HKU’s Medical Engineering Programme (which is retitled
to “Biomedical Engineering Programme” in 2018). He has worked in universities in the
United Kingdom (1991–1997), Singapore (1997–2002), and Hong Kong (2002–Present)
and has been a Guest Professor or Adjunct Professor of several universities in mainland China
(Shanghai Jiao Tong University, Zhejiang University, Tianjin University, Southwest Jiao tong
University, etc.). He was awarded BSc (1985) and Ph.D. (1991), both in Materials Science and
Engineering, by Shanghai Jiao Tong University and University of London, respectively. He is
a chartered engineer (CEng, 1995; UK) and chartered scientist (CSci, 2005; UK). He is an elec-
ted fellow of professional societies in the United Kingdom, Hong Kong, United States, and
internationally (FIMMM, 2001; FIMechE, 2007; FHKIE, 2010; FBSE, 2011; FAIMBE, 2012;
WAC Academician, 2013). Since 1991, he has been conducting research in biomaterials and
tissue engineering and developing new biomaterials using the composite/hybridization
approach. He was a founding member of UK’s Interdisciplinary Research Centre (IRC) in
Biomedical Materials at the University of London. His biomaterials research has covered
metals, polymers, ceramics, and composites and includes surface modification of materials or scaffolds. In recent years, he has
focused on nanobiomaterials, electrospinning, and 3D printing. He and his research staff/students have won many awards at inter-
national conferences. He has authored a large number of research papers as well as many book chapters. His research has been
widely cited by other researchers around the world. He has given many conference presentations, including more than 150 invited
talks at international conferences. He has also given more than 110 seminars in universities, research institutes, and hospitals in
Europe, North America, Asia, and Australia. He has been Chairman/Organizer of many conferences and has served in committees
of more than 70 international conferences. He is the Founding Series Editor of Springer Series in Biomaterials Science and Engineering
books and has been Editor, Associate Editor, or member of the Editorial Board of 20 international, printed journals, including Inter-
national Materials Reviews, Composites Science and Technology, Surface and Coatings Technology, Journal of Materials Science: Materials in
Medicine, and Journal of the Royal Society Interface. He has acted as a referee for more than 110 international journals in the fields of
materials science and engineering, biomaterials and tissue engineering, physics, chemistry, medicine, dentistry, medical devices,
biofabrication, nanoscience, nanotechnology, and 3D printing. He has been active in professional society activities and has served
in various roles in these societies. He was Chairman of the Biomedical Division of Hong Kong Institution of Engineers (HKIE). He
serves/has served in the Nomination Committee of World Academy of Ceramics (WAC) and the ICF-BSE Steering Committee of the
International College of Fellows of the International Union of Societies for Biomaterials Science and Engineering (IUS-BSE). He has
been an elected Council Member of Chinese Society for Biomaterials, Hong Kong Institution of Engineers, Asian Biomaterials Feder-
ation, World Association for Chinese Biomedical Engineers (WACBE), and Administrative Council of International Federation for
Medical and Biological Engineering (IFMBE). (http://web.hku.hk/memwang/).
Section Editors xiii
Alexander Wong
Alexander Wong, P.Eng., is currently the Canada Research Chair in Artificial Intelligence and
Medical Imaging, Codirector of the Vision and Image Processing Research Group, and an
Associate Professor in the Department of Systems Design Engineering at the University of
Waterloo. He had previously received the B.A.Sc. degree in Computer Engineering from
the University of Waterloo, Waterloo, ON, Canada, in 2005, the M.A.Sc. degree in Electrical
and Computer Engineering from the University of Waterloo, Waterloo, ON, Canada, in
2007, and Ph.D. degree in Systems Design Engineering from the University of Waterloo,
ON, Canada, in 2010. He was also an NSERC postdoctoral research fellow at Sunnybrook
Health Sciences Centre. He has published over 400 refereed journal and conference papers,
as well as patents, in various fields such as computational imaging, artificial intelligence,
computer vision, and medical imaging, and has received numerous awards such as 13 paper
awards at international conference and an Early Researcher Award from the Ministry of
Economic Development and Innovation.
Xiaojun Yu
Dr. Yu is Associate Professor, Biomedical Engineering at Stevens Institute of Technology,
Hoboken, NJ, United States. Dr. Yu’s primary research interests focus on tissue engineering,
polymeric biomaterials and drug delivery. His current research activities include nano- and
microscale functionalization of biomimic three-dimensional scaffolds for neural and
musculoskeletal tissue repair and regeneration, investigation of cell and material interac-
tions in bioreactors, development of controlled release systems for the delivery of growth
factors and drugs, and manipulation of microenvironment for stem cell proliferation and
differentiation.
CONTRIBUTORS TO VOLUME 1
Tyler Ackley M Bohner

UConn Health, Farmington, CT, United States RMS Foundation, Bettlach, Switzerland
Rafiq Ahmad M E Bronner
Chonbuk National University, Jeonju-si, Jeollabuk-do, California Institute of Technology, Pasadena, CA, USA
Republic of Korea
Ashley C Brown
Song Ih Ahn North Carolina State University and University of North
George W. Woodruff School of Mechanical Engineering, Carolina at Chapel Hill, Raleigh, NC, United States;
Wallace H. Coulter Department of Biomedical and North Carolina State University, Raleigh, NC,
Engineering, Institute for Electronics and United States
Nanotechnology, Parker H. Petit Institute for
Arnaud Bruyas
Bioengineering and Bioscience, Georgia Institute of
Stanford University, Stanford, CA, United States
Technology, Atlanta, GA, United States
S A Busch
Khiam Aik Khor
Athersys, Inc., Cleveland, OH, USA
Nanyang Technological University,
Singapore Ruth Cameron
University of Cambridge, Cambridge, United Kingdom
James M Anderson
Case Western Reserve University, Cleveland, OH, Sophie Cazalbou
United States UMR 5085 UPS-INPT-CNRS, Toulouse, France
Lavinia Cosmina Ardelean Paul Z Chen
“Victor Babes” University of Medicine and Pharmacy University of Waterloo, Waterloo, ON, Canada
Timisoara, Timisoara, Romania
Shiyu Cheng
A Atala Beijing Engineering Research Center for
Wake Forest Baptist Medical Center, WinstoneSalem, BioNanotechnology and CAS Key Laboratory for
NC, USA Biomedical Effects of Nanomaterials and Nanosafety,
CAS Center for Excellence in Nanoscience, National
S T Avecilla
Center for NanoScience and Technology, Beijing, P. R.
New York Presbyterian Hospital, Weill Cornell Medical
China
College, New York, NY, USA
Daniel Chester
Hani A Awad
North Carolina State University and University of North
University of Rochester, Rochester, NY, United States
Carolina at Chapel Hill, Raleigh, NC, United States;
Besim Ben-Nissan and North Carolina State University, Raleigh, NC,
University of Technology Sydney, Sydney, NSW, United States
Australia
Andy H Choi
Serena Best University of Technology Sydney, Sydney, NSW,
University of Cambridge, Cambridge, United Kingdom Australia
Aldo R Boccaccini Ezharul Hoque Chowdhury
University of Erlangen-Nuremberg, Erlangen, Germany Monash University, Clayton, VIC, Australia
xv
xvi Contributors to Volume 1
Tzahi Cohen-Karni Margaret A T Freeberg

Carnegie Mellon University, Pittsburgh, PA, United University of Rochester, Rochester, NY, United States
States
Katie Gailiunas
M Csete University of Connecticut, Storrs, CT, United States
Huntington Medical Research Institutes, Pasadena, CA,
Emmanuel Gibon
USA
M M Cushing Stuart B Goodman
New York Presbyterian Hospital, Weill Cornell Medical Stanford University, Stanford, CA, United States
College, New York, NY, USA
Paul Frank Gratzer
Michael A Daniele School of Biomedical Engineering, Dalhousie University,
North Carolina State University and University of North Halifax, NS, Canada
and North Carolina State University, Raleigh, NC, Frank X Gu
United States University of Waterloo, Waterloo, ON, Canada
Natalia Davidenko Vincenzo Guarino

University of Cambridge, Cambridge, United Kingdom National Research Council of Italy, Naples, Italy
Lin Guo
Caroline N Dealy
UConn Health, Farmington, CT, United States The University of Hong Kong, Pokfulam, Hong Kong
Babak Hassan Beygi
Jinqi Deng
The Hong Kong Polytechnic University of Hong Kong,
Beijing Engineering Research Center for
Hung Hom, Hong Kong
BioNanotechnology and CAS Key Laboratory for
Biomedical Effects of Nanomaterials and Nanosafety, Y Hayashi
CAS Center for Excellence in Nanoscience, National Department of Dental Regenerative Medicine, Center of
Center for NanoScience and Technology, Beijing, P. R. Advanced Medicine for Dental and Oral Diseases,
China; and Sino-Danish College, University of Chinese National Center for Geriatrics and Gerontology,
Academy of Sciences, Beijing, P. R. China Research Institute, Obu, Japan
Kyle G Doherty J S Hayes
University of Liverpool, Liverpool, United Kingdom NUI Galway, Galway, Ireland
Dionysios Douroumis Michelle Hobert
University of Greenwich, Greenwich, United Kingdom University of Connecticut, Storrs, CT, United States
Bin Duan T Hochgreb-Hägele
University of Nebraska Medical Center, Omaha, NE, California Institute of Technology, Pasadena, CA, USA
United States
Rong Huang
Felipe Eltit Queensland University of Technology, Brisbane, QLD,
The University of British Columbia, Vancouver, BC, Australia
Canada
K Ishida
Jorge Luis Escobar Ivirico Tokyo University of Science, Noda, Chiba, Japan
University of Connecticut, Storrs, CT, United States;
Manisha Jassal
and University of Connecticut Health Center,
Stevens Institute of Technology, Hoboken, NJ, United
Farmington, CT, United States
States
Bing Fang
Wenkai Jia
University of Delaware, Newark, DE, United States
Michigan Technological University, Houghton, MI,
Melanie Fisher United States
UConn Health, Farmington, CT, United States
Sirui Jiang
Kate Fox Case Western Reserve University, Cleveland, OH,
RMIT University, Melbourne, VIC, Australia United States
Contributors to Volume 1 xvii
Xingyu Jiang Dimitrios A Lamprou

Beijing Engineering Research Center for University of Kent, Canterbury, United Kingdom
BioNanotechnology and CAS Key Laboratory for
Cato T Laurencin
Biomedical Effects of Nanomaterials and Nanosafety,
University of Connecticut Health Center, Farmington,
CAS Center for Excellence in Nanoscience, National
CT, United States; and University of Connecticut,
Center for NanoScience and Technology, Beijing, P. R.
Storrs, CT, United States
China; and Sino-Danish College, University of Chinese
Academy of Sciences, Beijing, P. R. China Yunki Lee
Radoslaw Junka George W. Woodruff School of Mechanical Engineering,
Stevens Institute of Technology, Hoboken, NJ, United Wallace H. Coulter Department of Biomedical
States Engineering, Institute for Electronics and
Jacob G Kallenbach Bioengineering and Bioscience, Georgia Institute of
University of Rochester, Rochester, NY, United States Technology, Atlanta, GA, United States
Victoria R Kearns Andreas Lendlein
University of Liverpool, Liverpool, United Kingdom Institute of Biomaterial Science and Berlin Brandenburg
Stephnie M Kennedy Center for Regenerative Therapies, Teltow, Germany
University of Liverpool, Liverpool, United Kingdom Hannah J Levis
Yusuf Khan University of Liverpool, Liverpool, United Kingdom
University of Connecticut Health Center, Farmington,
Jiao Jiao Li
CT, United States
University of Sydney, Sydney, NSW, Australia; Kolling
Gilson Khang Institute, Northern Sydney Local Health District, St
Chonbuk National University, Jeonju-si, Jeollabuk-do, Leonards, NSW, Australia; and Sydney Medical School
Republic of Korea Northern, University of Sydney, St Leonards, NSW,
Australia
Kristi L Kiick
University of Delaware, Newark, DE, United States Zhong Li
Nanyang Technological University, Singapore
Sungwoo Kim
Stanford University, Stanford, CA, United States Liliana Liverani
University of Erlangen-Nuremberg, Erlangen,
YongTae Kim
Germany
George W. Woodruff School of Mechanical Engineering,
Wallace H. Coulter Department of Biomedical Thilanga Liyanage
Engineering, Institute for Electronics and University of Kentucky, Lexington, KY, United States
Tianzhi Luo
Bioengineering and Bioscience, Georgia Institute of
Technology, Atlanta, GA, United States
Christopher Mancuso
Nicholas J Kohrs
University of Connecticut, Storrs, CT, United States
University of Kentucky, Lexington, KY, United States
Ohan S Manoukian
D S Koslov
University of Connecticut Health, Farmington, CT,
Wake Forest Baptist Medical Center, WinstoneSalem,
United States; and University of Connecticut, Storrs,
NC, USA
CT, United States
Sangamesh G Kumbar
Ethan A Marrow
University of Connecticut Health, Farmington, CT,
North Carolina State University and University of North
United States; and University of Connecticut, Storrs,
CT, United States
and North Carolina State University, Raleigh, NC,
Vincenzo La Carrubba United States
University of Palermo, Palermo, Italy
Z Master
Rebecca Lace Albany Medical College, Albany, NY, USA; and
University of Liverpool, Liverpool, United Kingdom University of Alberta, Edmonton, AB, Canada
xviii Contributors to Volume 1
Stefani Mazzitelli David A Puleo

University of Ferrara, Ferrara, Italy University of Kentucky, Lexington, KY, United States
R Morita Zichen Qian
Tokyo University of Science, Noda, Chiba, Japan Michigan Technological University, Houghton, MI,
United States
Mahboob Morshed
Independent University, Dhaka, Bangladesh Ru Qing Yu
The University of Hong Kong, Hong Kong
Amir Najarzadeh
University of Kentucky, Lexington, KY, United States Daniel Radke
Michigan Technological University, Houghton, MI,
M Nakashima
United States
Department of Dental Regenerative Medicine, Center of
Advanced Medicine for Dental and Oral Diseases, P Rajan
National Center for Geriatrics and Gerontology, The Scripps Research Institute, La Jolla, CA, USA
Research Institute, Obu, Japan
Sahil Kumar Rastogi
Claudio Nastruzzi Carnegie Mellon University, Pittsburgh, PA, United
University of Ferrara, Ferrara, Italy States
Inn Chuan Ng Muhammad Y Razzaq
National University of Singapore, Singapore Institute of Biomaterial Science and Berlin Brandenburg
Center for Regenerative Therapies, Teltow, Germany
D H Nguyen
Shiley Eye Center and Institute for Genomic Medicine, Lucien Reclaru
University of California at San Diego, La Jolla, CA, USA VVSA, branch of Richemont International SA Varinor
Innovation, Delémont, Switzerland
Mitsuo Niinomi
Tohoku University, Sendai, Japan; Osaka University, Markus Reinthaler
Osaka, Japan; Meijo University, Nagoya, Japan; and Institute of Biomaterial Science and Berlin Brandenburg
Nagoya University, Nagoya, Japan Center for Regenerative Therapies, Teltow, Germany
Bridget Oei Nicholas P Rhodes
UConn Health, Farmington, CT, United States University of Liverpool, Liverpool, United Kingdom
Anurag Ojha Kelsey Richard
University of Connecticut, Storrs, CT, United States UConn Health, Farmington, CT, United States
M Oshima R G Richards
Tokyo University of Science, Noda, Chiba, Japan AO Research Institute, Davos, Switzerland
H Ouyang Aaqil Rifai
Shiley Eye Center and Institute for Genomic Medicine, RMIT University, Melbourne, VIC, Australia
University of California at San Diego, La Jolla, CA, USA
Steven A Ross
Chi-Chun Pan University of Greenwich, Greenwich, United Kingdom
M Saito
Pornteera Pawijit Tokyo University of Science, Noda, Chiba, Japan
National University of Singapore, Singapore
Naseem Sardashti
Aura Penalosa University of Connecticut Health, Farmington, CT,
University of Connecticut, Storrs, CT, United States United States; and University of Connecticut, Storrs,
CT, United States
D Pergament
Case Western Reserve University School of Law, Mark Schröder
Cleveland, OH, USA; and Children’s Law Group, LLC, Institute of Biomaterial Science and Berlin Brandenburg
Chicago, IL, USA Center for Regenerative Therapies, Teltow, Germany
Elena Pirogova Nikolaos Scoutaris
RMIT University, Melbourne, VIC, Australia University of Greenwich, Greenwich, United Kingdom
Contributors to Volume 1 xix
Swaminathan Sethuraman Mian Wang

SASTRA Deemed University, Thanjavur, India Northeastern University, Boston, MA, United States
Jeong Eun Song Min Wang
Chonbuk National University, Jeonju-si, Jeollabuk-do, The University of Hong Kong, Pokfulam, Hong Kong
Republic of Korea
Qiong Wang
Alexander Martin Stahl The University of British Columbia, Vancouver, BC,
Stanford University, Stanford, CA, United States Canada
Teagen Stedman Rizhi Wang
University of Connecticut Health, Farmington, CT, The University of British Columbia, Vancouver, BC,
United States Canada
Anuradha Subramanian Thomas J Webster
SASTRA Deemed University, Thanjavur, India Northeastern University, Boston, MA, United States;
Millicent O Sullivan and Wenzhou Medical University, Wenzhou, China
Rachel L Williams
Haoran Sun University of Liverpool, Liverpool, United Kingdom
Christian Wischke
Mitch Tahtinen Institute of Biomaterial Science and Berlin Brandenburg
Michigan Technological University, Houghton, MI, Center for Regenerative Therapies, Teltow, Germany
United States
Man Sang Wong
Jordon Tan The Hong Kong Polytechnic University of Hong Kong,
Temasek Polytechnic, Singapore Hung Hom, Hong Kong
A E Ting Yin Xiao
Athersys, Inc., Cleveland, OH, USA Queensland University of Technology, Brisbane, QLD,
Nirmalya Tripathy Australia
University of Washington, Seattle, WA, United States Yunzhi Yang
T Tsuji Stanford University, Stanford, CA, United States
Tokyo University of Science, Noda, Chiba, Japan; and Hanry Yu
Organ Technologies Inc., Tokyo, Japan National University of Singapore, Singapore; Agency for
N Turovets Science, Technology and Research (A*STAR),
University of California, Irvine, CA, USA Singapore; BioSyM, Singapore-MIT Alliance for
Research and Technology, Singapore; and Nanfang
Morgan A Urello Hospital, Southern Medical University, Guangzhou,
University of Delaware, Newark, DE, United States China
Antonio Valdevit
Xiaojun Yu
Stevens Institute of Technology, Hoboken, NJ, United Stevens Institute of Technology, Hoboken, NJ, United
States; and SEA Limited, Columbus, OH, United States
States
Nandakumar Venkatesan
K Zhang
University of Kentucky, Lexington, KY, United States
Shiley Eye Center and Institute for Genomic Medicine,
Chong Wang University of California at San Diego, La Jolla, CA, USA
Dongguan University of Technology, Dongguan, China
Feng Zhao
Guifang Wang Michigan Technological University, Houghton, MI,
Michigan Technological University, Houghton, MI, United States
United States
Qilong Zhao
Jing Yi Wang Shenzhen Institutes of Advanced Technology, Chinese
The University of Hong Kong, Hong Kong Academy of Sciences, Shenzhen, China
xx Contributors to Volume 1
Li Wu Zheng Yu Zheng
Prince Philip Dental Hospital, The University of Hong The Hong Kong Polytechnic University of Hong Kong,
Kong, Hong Kong Hung Hom, Hong Kong
Wenfu Zheng Yinghong Zhou
Beijing Engineering Research Center for Queensland University of Technology, Brisbane, QLD,
BioNanotechnology and CAS Key Laboratory for Australia
Biomedical Effects of Nanomaterials and Nanosafety,
CAS Center for Excellence in Nanoscience, National Hala Zreiqat
Center for NanoScience and Technology, Beijing, P. R. University of Sydney, Sydney, NSW, Australia
China
CONTENTS OF VOLUME 1
Editorial Board v
Editor in Chief vii
Section Editors ix
Contents of All Volumes xxv
Preface xxxv
Biomaterials: Science and Engineering

Alternative Processing Techniques for CoCr Dental Alloys 1
Lucien Reclaru and Lavinia Cosmina Ardelean
Bioceramics 16
Besim Ben-Nissan, Sophie Cazalbou, and Andy H Choi
Biomedical Composites 34
Min Wang and Qilong Zhao
Bulk Properties of Biomaterials and Testing Techniques 53
Min Wang and Chong Wang
Corrosion of Orthopedic Implants 65
Qiong Wang, Felipe Eltit, and Rizhi Wang
Decellularized Extracellular Matrix 86
Paul Frank Gratzer
Diamond, Carbon Nanotubes and Graphene for Biomedical Applications 97
Aaqil Rifai, Elena Pirogova, and Kate Fox
Gold Nanoparticles for Colorimetric Detection of Pathogens 108
Paul Z Chen and Frank X Gu
Manufacture of Biomaterials 116
Min Wang, Lin Guo, and Haoran Sun
Materials and Their Biomedical Applications 135
Min Wang and Bin Duan
Nano-Biomaterials and their Applications 153
Mian Wang and Thomas J Webster
xxi
xxii Contents of Volume 1
Natural Biopolymers for Biomedical Applications 162

Natalia Davidenko, Ruth Cameron, and Serena Best
Polymeric Coatings and Their Fabrication for Medical Devices 177
Dimitrios A Lamprou, Nikolaos Scoutaris, Steven A Ross, and Dionysios Douroumis
Porous Biomaterials and Scaffolds for Tissue Engineering 188
Liliana Liverani, Vincenzo Guarino, Vincenzo La Carrubba, and Aldo R Boccaccini
Preparation and Properties of Coatings and Thin Films on Metal Implants 203
Zhong Li and Khiam Aik Khor
Titanium Alloys 213
Mitsuo Niinomi
Biomaterials: In Vitro and in Vivo Studies of Biomaterials

Anatomy and Physiology for Biomaterials Research and Development 225
Inn Chuan Ng, Pornteera Pawijit, Jordon Tan, and Hanry Yu
Animal Models in Biomaterial Development 237
James M Anderson and Sirui Jiang
Blood–Biomaterial Interactions 242
Nicholas P Rhodes
Interaction Between Mesenchymal Stem Cells and Immune Cells in Tissue Engineering 249
Rong Huang, Yinghong Zhou, and Yin Xiao
Osseointegration of Permanent and Temporary Orthopedic Implants 257
J S Hayes and R G Richards
Tissue Response to Biomaterials 270
Jiao Jiao Li and Hala Zreiqat
Biomaterials: Biomaterial Applications and Advanced Medical Technologies

Biomaterials in Dentistry 278
Li Wu Zheng, Jing Yi Wang, and Ru Qing Yu
Biomaterials in Ophthalmology 289
Rachel L Williams, Hannah J Levis, Rebecca Lace, Kyle G Doherty, Stephnie M Kennedy, and Victoria R Kearns
Biomaterials in Orthopaedics 301
Emmanuel Gibon and Stuart B Goodman
Cell Encapsulation and Delivery 308
Stefani Mazzitelli and Claudio Nastruzzi
Drug Delivery Systems and Controlled Release 316
Nicholas J Kohrs, Thilanga Liyanage, Nandakumar Venkatesan, Amir Najarzadeh, and David A Puleo
Electrospinning and Electrospray for Biomedical Applications 330
Gene Delivery and Clinical Applications 345
Mahboob Morshed and Ezharul Hoque Chowdhury
Materials for Exoskeletal Orthotic and Prosthetic Systems 352
Man Sang Wong, Babak Hassan Beygi, and Yu Zheng
Contents of Volume 1 xxiii
Microfluidics for Biomedical Applications 368

Shiyu Cheng, Jinqi Deng, Wenfu Zheng, and Xingyu Jiang
Organs-on-Chips 384
Yunki Lee, Song Ih Ahn, and YongTae Kim
Shape-Memory Polymer Medical Devices 394
Muhammad Y Razzaq, Markus Reinthaler, Mark Schröder, Christian Wischke, and Andreas Lendlein
Regenerative Engineering
Adult Bone Marrow-Derived Stem Cells: Immunomodulation in the Context of Disease and Injury 406
A E Ting and S A Busch
Assessment of Cellular Responses of Tissue Constructs in vitro in Regenerative Engineering 414
Margaret A T Freeberg, Jacob G Kallenbach, and Hani A Awad
Assessment of Tissue Constructs In Vivo in Regenerative Engineering 427
Anuradha Subramanian and Swaminathan Sethuraman
Bioengineered Kidney and Bladder 432
D S Koslov and A Atala
Bioengineering Scaffolds for Regenerative Engineering 444
Zichen Qian, Daniel Radke, Wenkai Jia, Mitch Tahtinen, Guifang Wang, and Feng Zhao
Biomaterials for Tissue Engineering and Regenerative Medicine 462
Ohan S Manoukian, Naseem Sardashti, Teagen Stedman, Katie Gailiunas, Anurag Ojha,
Aura Penalosa, Christopher Mancuso, Michelle Hobert, and Sangamesh G Kumbar
Biomimetic Approaches for Regenerative Engineering 483
Nirmalya Tripathy, Rafiq Ahmad, Jeong Eun Song, and Gilson Khang
Bioreactors: System Design and Application for Regenerative Engineering 496
Antonio Valdevit
Bone Substitute Materials 513
M Bohner
Case Studies for Soft Tissue Regenerative Engineering 530
Jorge Luis Escobar Ivirico and Cato T Laurencin
Characterizing the Properties of Tissue Constructs for Regenerative Engineering 537
Yusuf Khan
Clinical and Laboratory Aspects of Hematopoietic Stem Cell Transplantation 546
S T Avecilla and M M Cushing
Dental Stem Cells 554
M Nakashima and Y Hayashi
Drug and Gene Delivery for Regenerative Engineering 565
Morgan A Urello, Tianzhi Luo, Bing Fang, Kristi L Kiick, and Millicent O Sullivan
Ethics of Issues and Stem Cell Research: the Unresolved Issues 584
Z Master
Eye Diseases and Stem Cells 598
H Ouyang, D H Nguyen, and K Zhang
xxiv Contents of Volume 1
Human Parthenogenetic Pluripotent Stem Cells 608

N Turovets and M Csete
Human Pluripotent Stem Cells 618
P Rajan
Introduction to Regenerative Engineering 624
Manisha Jassal, Radoslaw Junka, Cato T Laurencin, and Xiaojun Yu
Nanoelectronics for Neuroscience 631
Sahil Kumar Rastogi and Tzahi Cohen-Karni
Neural Crest Stem Cells 650
T Hochgreb-Hägele and M E Bronner
Osteoarthritis at the Cellular Level: Mechanisms, Clinical Perspectives, and Insights From Development 660
Melanie Fisher, Tyler Ackley, Kelsey Richard, Bridget Oei, and Caroline N Dealy
Reproductive Technologies, Assisted 677
D Pergament
Tooth Regenerative Therapy: Tooth Tissue Repair and Whole Tooth Replacement 686
M Oshima, K Ishida, R Morita, M Saito, and T Tsuji
Vascularized Tissue Regenerative Engineering Using 3D Bioprinting Technology 696
Sungwoo Kim, Arnaud Bruyas, Chi-Chun Pan, Alexander Martin Stahl, and Yunzhi Yang
Wound Healing and the Host Response in Regenerative Engineering 707
Daniel Chester, Ethan A Marrow, Michael A Daniele, and Ashley C Brown
CONTENTS OF ALL VOLUMES
VOLUME 1
Biomaterials: Science and Engineering
Alternative Processing Techniques for CoCr Dental Alloys 1
Lucien Reclaru and Lavinia Cosmina Ardelean
Bioceramics 16
Besim Ben-Nissan, Sophie Cazalbou, and Andy H Choi
Biomedical Composites 34
Bulk Properties of Biomaterials and Testing Techniques 53
Min Wang and Chong Wang
Corrosion of Orthopedic Implants 65
Qiong Wang, Felipe Eltit, and Rizhi Wang
Decellularized Extracellular Matrix 86
Paul Frank Gratzer
Diamond, Carbon Nanotubes and Graphene for Biomedical Applications 97
Aaqil Rifai, Elena Pirogova, and Kate Fox
Gold Nanoparticles for Colorimetric Detection of Pathogens 108
Paul Z Chen and Frank X Gu
Manufacture of Biomaterials 116
Min Wang, Lin Guo, and Haoran Sun
Materials and Their Biomedical Applications 135
Min Wang and Bin Duan
Nano-Biomaterials and their Applications 153
Mian Wang and Thomas J Webster
Natural Biopolymers for Biomedical Applications 162
Natalia Davidenko, Ruth Cameron, and Serena Best
Polymeric Coatings and Their Fabrication for Medical Devices 177
Dimitrios A Lamprou, Nikolaos Scoutaris, Steven A Ross, and Dionysios Douroumis
xxv
xxvi Contents of All Volumes
Porous Biomaterials and Scaffolds for Tissue Engineering 188

Liliana Liverani, Vincenzo Guarino, Vincenzo La Carrubba, and Aldo R Boccaccini
Preparation and Properties of Coatings and Thin Films on Metal Implants 203
Zhong Li and Khiam Aik Khor
Titanium Alloys 213
Mitsuo Niinomi
Biomaterials: In Vitro and in Vivo Studies of Biomaterials

Anatomy and Physiology for Biomaterials Research and Development 225
Inn Chuan Ng, Pornteera Pawijit, Jordon Tan, and Hanry Yu
Animal Models in Biomaterial Development 237
James M Anderson and Sirui Jiang
Blood–Biomaterial Interactions 242
Nicholas P Rhodes
Interaction Between Mesenchymal Stem Cells and Immune Cells in Tissue Engineering 249
Rong Huang, Yinghong Zhou, and Yin Xiao
Osseointegration of Permanent and Temporary Orthopedic Implants 257
J S Hayes and R G Richards
Tissue Response to Biomaterials 270
Jiao Jiao Li and Hala Zreiqat
Biomaterials: Biomaterial Applications and Advanced Medical Technologies

Biomaterials in Dentistry 278
Li Wu Zheng, Jing Yi Wang, and Ru Qing Yu
Biomaterials in Ophthalmology 289
Rachel L Williams, Hannah J Levis, Rebecca Lace, Kyle G Doherty, Stephnie M Kennedy, and Victoria R Kearns
Biomaterials in Orthopaedics 301
Emmanuel Gibon and Stuart B Goodman
Cell Encapsulation and Delivery 308
Stefani Mazzitelli and Claudio Nastruzzi
Drug Delivery Systems and Controlled Release 316
Nicholas J Kohrs, Thilanga Liyanage, Nandakumar Venkatesan, Amir Najarzadeh, and David A Puleo
Electrospinning and Electrospray for Biomedical Applications 330
Gene Delivery and Clinical Applications 345
Mahboob Morshed and Ezharul Hoque Chowdhury
Materials for Exoskeletal Orthotic and Prosthetic Systems 352
Man Sang Wong, Babak Hassan Beygi, and Yu Zheng
Microfluidics for Biomedical Applications 368
Shiyu Cheng, Jinqi Deng, Wenfu Zheng, and Xingyu Jiang
Organs-on-Chips 384
Yunki Lee, Song Ih Ahn, and YongTae Kim
Contents of All Volumes xxvii
Shape-Memory Polymer Medical Devices 394

Muhammad Y Razzaq, Markus Reinthaler, Mark Schröder, Christian Wischke, and Andreas Lendlein
Regenerative Engineering
Adult Bone Marrow-Derived Stem Cells: Immunomodulation in the Context of Disease and Injury 406
A E Ting and S A Busch
Assessment of Cellular Responses of Tissue Constructs in vitro in Regenerative Engineering 414
Margaret A T Freeberg, Jacob G Kallenbach, and Hani A Awad
Assessment of Tissue Constructs In Vivo in Regenerative Engineering 427
Anuradha Subramanian and Swaminathan Sethuraman
Bioengineered Kidney and Bladder 432
D S Koslov and A Atala
Bioengineering Scaffolds for Regenerative Engineering 444
Zichen Qian, Daniel Radke, Wenkai Jia, Mitch Tahtinen, Guifang Wang, and Feng Zhao
Biomaterials for Tissue Engineering and Regenerative Medicine 462
Ohan S Manoukian, Naseem Sardashti, Teagen Stedman, Katie Gailiunas, Anurag Ojha,
Aura Penalosa, Christopher Mancuso, Michelle Hobert, and Sangamesh G Kumbar
Biomimetic Approaches for Regenerative Engineering 483
Nirmalya Tripathy, Rafiq Ahmad, Jeong Eun Song, and Gilson Khang
Bioreactors: System Design and Application for Regenerative Engineering 496
Antonio Valdevit
Bone Substitute Materials 513
M Bohner
Case Studies for Soft Tissue Regenerative Engineering 530
Jorge Luis Escobar Ivirico and Cato T Laurencin
Characterizing the Properties of Tissue Constructs for Regenerative Engineering 537
Yusuf Khan
Clinical and Laboratory Aspects of Hematopoietic Stem Cell Transplantation 546
S T Avecilla and M M Cushing
Dental Stem Cells 554
M Nakashima and Y Hayashi
Drug and Gene Delivery for Regenerative Engineering 565
Morgan A Urello, Tianzhi Luo, Bing Fang, Kristi L Kiick, and Millicent O Sullivan
Ethics of Issues and Stem Cell Research: the Unresolved Issues 584
Z Master
Eye Diseases and Stem Cells 598
H Ouyang, D H Nguyen, and K Zhang
Human Parthenogenetic Pluripotent Stem Cells 608
N Turovets and M Csete
Human Pluripotent Stem Cells 618
P Rajan
xxviii Contents of All Volumes
Introduction to Regenerative Engineering 624

Manisha Jassal, Radoslaw Junka, Cato T Laurencin, and Xiaojun Yu
Nanoelectronics for Neuroscience 631
Sahil Kumar Rastogi and Tzahi Cohen-Karni
Neural Crest Stem Cells 650
T Hochgreb-Hägele and M E Bronner
Osteoarthritis at the Cellular Level: Mechanisms, Clinical Perspectives, and Insights From Development 660
Melanie Fisher, Tyler Ackley, Kelsey Richard, Bridget Oei, and Caroline N Dealy
Reproductive Technologies, Assisted 677
D Pergament
Tooth Regenerative Therapy: Tooth Tissue Repair and Whole Tooth Replacement 686
M Oshima, K Ishida, R Morita, M Saito, and T Tsuji
Vascularized Tissue Regenerative Engineering Using 3D Bioprinting Technology 696
Sungwoo Kim, Arnaud Bruyas, Chi-Chun Pan, Alexander Martin Stahl, and Yunzhi Yang
Wound Healing and the Host Response in Regenerative Engineering 707
Daniel Chester, Ethan A Marrow, Michael A Daniele, and Ashley C Brown
VOLUME 2
Biomechanics
Biomechanics of Cells as Potential Biomarkers for Diseases: A New Tool in Mechanobiology 1
Dinesh R Katti, Kalpana S Katti, Shahjahan Molla, and Sumanta Kar
Bone Micro- and Nanomechanics 22
Caitlyn J Collins, Orestis G Andriotis, Vedran Nedelkovski, Martin Frank, Orestis L Katsamenis, and
Philipp J Thurner
Cell Adhesion: Basic Principles and Computational Modeling 45
Diego A Vargas and Hans Van Oosterwyck
Centrifugation and Hypergravity in the Bone 59
Carmelo Mastrandrea and Laurence Vico
Computational Modeling of Respiratory Biomechanics 70
Christian J Roth, Lena Yoshihara, and Wolfgang A Wall
Constitutive Modeling of Soft Tissues 81
Michele Marino
Continuum Mechanics and Its Practical Applications at the Level of Scaling Laws 111
Ko Okumura
CT-Based Bone and Muscle Assessment in Normal and Pathological Conditions 119
Paolo Gargiulo, Magnus K Gislason, Kyle J Edmunds, Jonathan Pitocchi, Ugo Carraro, Luca Esposito,
Massimiliano Fraldi, Paolo Bifulco, Mario Cesarelli, and Halldór Jónsson
Knowledge Extraction From Medical Imaging for Advanced Patient-Specific Musculoskeletal Models 135
Marie-Christine Ho Ba Tho and Tien Tuan Dao
Contents of All Volumes xxix
Mathematical Quantification of the Impact of Microstructure on the Various Effective

Properties of Bones 143
Miao-Jung Y Ou, Annalisa De Paolis, and Luis Cardoso
Multiphase Porous Media Models for Mechanics in Medicine: Applications to Transport Oncophysics
and Diabetic Foot 155
Pietro Mascheroni, Raffaella Santagiuliana, and Bernhard Schrefler
Multiscale Bone Mechanobiology 167
Stefan Scheiner, Maria-Ioana Pastrama, Peter Pivonka, and Christian Hellmich
Multiscale Mechanical Behavior of Large Arteries 180
Claire Morin, Witold Krasny, and Stéphane Avril
Nanoindentation-Based Characterization of Hard and Soft Tissues 203
Pasquale Vena and Dario Gastaldi
Nanomechanical Raman Spectroscopy in Biological Materials 215
Yang Zhang, Ming Gan, and Vikas Tomar
On the Use of Population-Based Statistical Models in Biomechanics 229
Justin Fernandez, Shasha Yeung, Alex Swee, Marco Schneider, Thor Besier, and Ju Zhang
Poroelasticity of Living Tissues 238
Andrea Malandrino and Emad Moeendarbary
Structural and Material Changes of Human Cortical Bone With Age: Lessons from the Melbourne
Femur Research Collection 246
Romane Blanchard, C David L Thomas, Rita Hardiman, John G Clement, David C Cooper, and
Peter Pivonka
Vascular Tissue Biomechanics: Constitutive Modeling of the Arterial Wall 265
Thomas Christian Gasser
Medical Devices
3D Printing in the Biomedical Field 275
Alexander K Nguyen, Roger J Narayan, and Ashkan Shafiee
Biocompatibility Evaluation of Orthopedic Biomaterials and Medical Devices: A Review of Safety
and Efficacy Models 281
Michel Assad and Nicolette Jackson
Biological Grafts: Surgical Use and Vascular Tissue Engineering Options for Peripheral Vascular Implants 310
Francesca Boccafoschi, Martina Ramella, Luca Fusaro, Marta C Catoira, and Francesco Casella
Current Advancements and Challenges in Stent-Mediated Gene Therapy 322
Shounak Ghosh, Katari Venkatesh, and Dwaipayan Sen
Dentistry: Restorative and Regenerative Approaches 332
Geetha Manivasagam, Aakash Reddy, Dwaipayan Sen, Sunita Nayak, Mathew T Mathew, and
Asokami Rajamanikam
Ephemeral Biogels: Potential Applications as Active Dressings and Drug Delivery Devices 348
Larreta-Garde Véronique, Picard Julien, and Giraudier Sébastien
Immunological Responses in Orthopedics and Transplantation 359
Caroline D Hoemann and Martin Guimond
xxx Contents of All Volumes
Iron-Based Degradable Implants 374

Sergio Loffredo, Carlo Paternoster, and Diego Mantovani
Medical Devices: Coronary Stents 386
Vanessa Montaño-Machado, Malgorzata Sikora-Jasinska, Carolina Catanio Bortolan, Pascale Chevallier,
and Diego Mantovani
Medical Devices in Otorhinolaryngology 399
Paolo Aluffi Valletti, Massimiliano Garzaro, and Valeria Dell’Era
Medical Devices in Neurology 409
Abbas Z Kouzani and Roy V Sillitoe
Obstetrics and Gynecology: Hysteroscopy 414
Antonio Santos-Paulo
Orthopedic Implants 425
Weihong Jin and Paul K Chu
Pharmacology: Drug Delivery 440
Frédéric Chaubet, Violeta Rodriguez-Ruiz, Michel Boissière, and Diego Velasquez
Prosthetic Aortic Valves 454
Anne-Sophie Zenses, Philippe Pibarot, Marie-Annick Clavel, Ezequiel Guzzetti, Nancy Cote, and Erwan Salaun
Urology and Nephrology: Regenerative Medicine Applications 467
Ingrid Saba, Stéphane Chabaud, Sophie Ramsay, Hazem Orabi, and Stéphane Bolduc
Zinc-Based Degradable Implants 478
Ehsan Mostaed, Malgorzata Sikora-Jasinska, and Maurizio Vedani
Medical Imaging
Biomechanics Imaging and Analysis 488
Reza Sharif Razavian, Sara Greenberg, and John McPhee
Breast Imaging: Mammography, Digital Tomosynthesis, Dynamic Contrast Enhancement 501
Mehran Ebrahimi
Diffusion Magnetic Resonance Imaging 505
Jennifer Shane Williamson Campbell and Gilbert Bruce Pike
Digital Holographic Microscopy 519
Farnoud Kazemzadeh and Alexander Wong
Digital Pathology 524
Matthew G Hanna and Liron Pantanowitz
Functional Magnetic Resonance Imaging 533
Jean Chen and Julien Cohen-Adad
Hemodynamic Imaging 545
Robert Amelard and Alexander Wong
Imaging Informatics 551
David A Koff and Thomas E Doyle
Macroscopic Pigmented Skin Lesion Prescreening 561
Eliezer Bernart, Eliezer Soares Flores, and Jacob Scharcanski
Contents of All Volumes xxxi
Magnetic Resonance Imaging 574

Rachel W Chan, Justin Y C Lau, Wilfred W Lam, and Angus Z Lau
Perceptual Quality Assessment of Medical Images 588
Hantao Liu and Zhou Wang
Radiomics 597
Farzad Khalvati, Yucheng Zhang, Alexander Wong, and Masoom A Haider
Ultrasound Elastography 604
Hyock Ju Kwon and Bonghun Shin
Rehabilitation Engineering and Integrative Technologies

Functional Electric Stimulation Therapy 614
Dejan B Popovic
ProsthesesdAssistive TechnologydSports 621
Bryce T J Dyer
ProsthesesdAssistive TechnologydUpper 632
Jonathon W Sensinger, Wendy Hill, and Michelle Sybring
Robotics: Exoskeletons 645
Daniel P Ferris, Bryan R Schlink, and Aaron J Young
RoboticsdSoft Robotics 652
Gursel Alici
VOLUME 3
Mathematical Techniques in Biomedical Engineering

Cardiac Modeling 1
Edward Vigmond and Gernot Plank
Mathematical Approaches for Medical Image Registration 21
Barbara Zitova
Mathematical Modeling of Gene Networks 33
Lakshmi Sugavaneswaran
Mathematical Modeling Tools and Software for BME Applications 56
Fred J Vermolen and Amit Gefen
Mathematical Techniques for Biomedical Image Segmentation 64
Roberto Rodríguez and Juan H Sossa
Mathematical Techniques for Circulatory Systems 79
Jason Carson, Raoul Van Loon, and Perumal Nithiarasu
Mathematical Techniques for Noninvasive Muscle Signal Analysis and Interpretation 95
Roberto Merletti, Ales Holobar, and Dario Farina
Optimization Techniques in BME 112
Jeevan Kumar Pant
xxxii Contents of All Volumes
Single-Cell-Based In Silico Models: A Tool for Dissecting Tumor Heterogeneity 130

Aleksandra Karolak, Saharsh Agrawal, Samantha Lee, and Katarzyna A Rejniak
Spectrotemporal Modeling of Biomedical Signals: Theoretical Foundation and Applications 144
Raymundo Cassani and Tiago H Falk
Statistical Modeling in Biomedical Engineering 164
Yunfeng Wu and Pinnan Chen
Time–Frequency Distributions in Biomedical Signal Processing 177
Yashodhan Athavale and Sridhar Krishnan
Wavelets in Biomedical Signal Processing and Analysis 193
Babak Azmoudeh and Dean Cvetkovic
Bioinstrumentation and Bioinformatics

A Systematic Workflow for Design and Computational Analysis of Protein Microarrays 213
Jonatan Fernández-García, Rodrigo García-Valiente, Javier Carabias-Sánchez, Alicia Landeira-Viñuela,
Rafael Góngora, María Gonzalez-Gonzalez, and Manuel Fuentes
Ambulatory EEG Monitoring 223
Bernard Grundlehner and Vojkan Mihajlovic
Automated EEG Analysis for Neonatal Intensive Care 240
Nathan Stevenson and Anton Tokariev
Big Data Calls for Machine Learning 258
Andreas Holzinger
Bioimpedance Spectroscopy Processing and Applications 265
Herschel Caytak, Alistair Boyle, Andy Adler, and Miodrag Bolic
Bioinformatics in Design of Antiviral Vaccines 280
Ashesh Nandy and Subhash C Basak
Bioinformatics in Disease Classification 291
Miguel Ángel Medina
Biopotential Monitoring 296
Julián Oreggioni, Angel A Caputi, and Fernando Silveira
Blood Gas Analysis and Instrumentation 305
Rebecca Symons, Robindro Chatterji, Kirsty Whenan, Rita Horvath, and Paul S Thomas
Computational Approaches in microRNA Biology 317
Ulf Schmitz, Shailendra K Gupta, Julio Vera, and Olaf Wolkenhauer
Detection and Classification of Breast Lesions Using Ultrasound-Based Imaging Modalities 331
Md Kamrul Hasan and Sharmin R Ara
DNA Microarrays: Fundamentals, Data Integration and Applications 349
Eduardo Valente and Miguel Rocha
ECG Monitoring: Present Status and Future Trend 363
Saurabh Pal
Genetic Algorithms for Breast Cancer Diagnostics 380
Florin Gorunescu and Smaranda Belciug
Contents of All Volumes xxxiii
Machine Learning in Biomedical Informatics 389

Carlos Fernandez-Lozano, Adrián Carballal, Cristian R Munteanu, Marcos Gestal, Víctor Maojo,
and Alejandro Pazos
Matrix Assisted Laser Desorption/Ionization as a New Cancer Diagnostic Tool 400
Bozena Hosnedlova, Marta Kepinska, Branislav Ruttkay-Nedecky, Carlos Fernandez, Tomas Parak,
Halina Milnerowicz, Jiri Sochor, Geir Bjørklund, and Rene Kizek
Medical Utility of NIR Monitoring 415
Zuzana Kovacsova, Gemma Bale, and Ilias Tachtsidis
Metabolomics in Biomaterial Research 432
Ana M Gil, Maria H Fernandes, and Iola F Duarte
Nucleic-Acid Sequencing 443
G Dorado, S Gálvez, H Budak, T Unver, and P Hernández
Optical Techniques for Blood and Tissue Oxygenation 461
Panayiotis Kyriacou, Karthik Budidha, and Tomas Y Abay
Polymerase Chain Reaction (PCR) 473
G Dorado, G Besnard, T Unver, and P Hernández
Single-Photon Emission Computed Tomography: Principles and Applications 493
Yong Du and Habib Zaidi
Translational Bioinformatics: Informatics, Medicine, and -Omics 507
Sergio Paraiso-Medina, David Perez-Rey, Raul Alonso-Calvo, Cristian R Munteanu, Alejandro Pazos,
Casimir A Kulikowski, and Victor Maojo
Ultrasonic Imaging in Biomedical Applications 515
Roman Gr Maev and Fedar M Severin
Index 523
PREFACE
The use by man of available technology to treat damaged or diseased tissue is older than the written historical
record. For example, the Mayan people created artificial teeth out of nacre, which were shown to be fused to the
bone (Bobbio, 1972; Westbroek & Marin, 1998). Giovanni Borelli’s studies of the cardiovascular system (e.g.,
the elasticity of arteries), which were published in De Motu Animalium (On Animal Motion), can be considered
as one of the foundations of the field of biomechanics (Parker, 2009). The hypothesis of an intrinsic ’animal
electricity’ by Luigi Galvani in the 18th century led to the development of the field of electrophysiology (Pic-
colino, 1997). In the 19th century, the development of the antiseptic approach to surgical procedures by Joseph
Lister made implantation of medical devices without certain postoperative infection possible; for example,
Lister described the use of silver wire for treatment of a fractured patella (Worboys, 2013). The discovery of X-
rays by Roentgen at the end of the 19th century was rapidly translated for medical imaging (Rowland, 1896;
Schuster, 1896). In our lifetime, the work by W. T. Green on generating new cartilage by seeding of chondrocytes
as well as by John Burke and Ioannis Yannas on generating skin substitutes is recognized as the birth of the field
of regenerative engineering (Vacanti, 2006).
At the beginning of the 21st century, the American Institute for Medical and Biological Engineering
identified several research areas for the field of biomedical engineering. These include: (a) functional geno-
mics and proteomics, (b) nanotechnology, (c) targeted drug delivery, (d) tissue engineering, and (e) the
development of new types of medical instrumentation (Hendee, Chien, Maynard, & Dean, 2002). As some of
these research areas have matured, others have become more prominent. Over the past few years, the use of
3D printing and bioprinting technologies to create medical devices has become more prominent. One benefit
of utilizing 3D printing and bioprinting for patient care is that medical imaging data (e.g., magnetic resonance
imaging and computed tomography data) may be employed to fashion prostheses or artificial tissues with
submicroscale features that conform with the requirements of the patient (Narayan, Doraiswamy, Chrisey, &
Chichkov, 2010; Skoog & Narayan, 2013). Another technology that will likely transform the field of
biomedical engineering over the coming decades involves the use of clustered regularly interspaced short
palindromic repeats (CRISPR)/Cas9 for engineering of the human genome. The interface between biomedical
engineering and the new field of genome engineering has already spawned research into new technologies for
delivery of genome editing tools into the body; the synergy between these fields will only grow over time
(Wright, Nuñez, & Doudna, 2016).
The goal of the Encyclopedia of Biomedical Engineering is to consider the principles and technologies that
underlie the field of biomedical engineering. The encyclopedia is divided into three volumes. The first volume
contains a section on biomaterials, which was edited by Min Wang at the University of Hong Kong, and
a section on regenerative engineering, which was edited by Cato Laurencin at the University of Connecticut and
Xiaojun Yu at the Stevens Institute of Technology. The second volume contains a section on rehabilitation
engineering and integrative technologies, which was edited by William Rymer and Levi Hargrove at North-
western University, a section on biomechanics, which was edited by Christian Hellmich at the Vienna University
of Technology, a section on medical devices, which was edited by Diego Mantovani at the University of Laval,
and a section on medical imaging, which was edited by Alexander Wong at the University of Waterloo. The third
volume contains a section on mathematical techniques in biomedical engineering, which was edited by Sri
Krishnan at Ryerson University, and a section on bioinstrumentation and bioinformatics, which was edited by
Pankaj Vadgama at Queen Mary University of London.
I would like express my sincere appreciation to the section editors and authors for all of their efforts on the
encyclopedia. I would also like thank Beckie Brand, Susan Dennis, Becky Gelson, Ginny Mills, Blerina Osmanaj,
xxxv
xxxvi Preface
Laura Escalante Santos, and Will Smaldon at Elsevier for their outstanding efforts to bring the encyclopedia to
publication. I hope that this work serves the biomedical engineering community by providing a resource that
considers topics at the interface of the biological sciences and engineering.
Roger J Narayan, M.D., Ph.D.

UNC/NCSU Joint Department of Biomedical Engineering.
References
Bobbio, A. (1972). The first endosseous alloplastic implant in the history of man. Bull. Hist. Dent, 20, 1–6.
Hendee, W. R., Chien, S., Maynard, C. D., & Dean, D. J. (2002). The National Institute of biomedical imaging and Bioengineering: history, status, and potential impact. Annals of
Biomedical Engineering, 30, 2–10.
Narayan, R. J., Doraiswamy, A., Chrisey, D. B., & Chichkov, B. N. (2010). Medical prototyping using two photon polymerization. Materials Today, 13, 44–50.
Parker, K. H. (February 2009). A brief history of arterial wave mechanics. Medical & Biological Engineering & Computing, 47(2), 111–118.
Piccolino, M. (October 1997). Luigi Galvani and animal electricity: two centuries after the foundation of electrophysiology. Trends in Neurosciences, 20(10), 443–448.
Rowland, S. (March 7, 1896). Report on the Application of the new Photography to medicine and surgery. Br Med J, 1(1836), 620–622.
Schuster, A. (January 18, 1896). On the new Kind of Radiation. Br Med J, 1(1829), 172–173.
Skoog, S. A., & Narayan, R. J. (2013). Stereolithography in medical device fabrication. Advanced Materials & Processes, 171, 32–36.
Vacanti, C. A. (July 2006). The history of tissue engineering. J Cell Mol Med, 10(3), 569–576.
Westbroek, P., & Marin, F. (1998). A marriage of bone and nacre. Nature, 392, 861–862.
Worboys, M. (September 20, 2013). Joseph Lister and the performance of antiseptic surgery. Notes and Records of the Royal Society of London, 67(3), 199–209.
Wright, A. V., Nuñez, J. K., & Doudna, J. A. (January 14, 2016). Biology and Applications of CRISPR systems: Harnessing Nature’s Toolbox for genome engineering. Cell, 164(1–2),
29–44.
PERMISSION ACKNOWLEDGMENTS
The following material is reproduced with kind permission of Taylor & Francis
Figure 1 On the Use of Population-Based Statistical Models in Biomechanics

www.taylorandfrancisgroup.com
The following material is reproduced with kind permission of American Association for the Advancement of
Science
Figure 8a Nanotechnology for Regenerative Engineering

www.aaas.org
The following material is reproduced with kind permission of Oxford University Press
Figure 1 Translational Bioinformatics for Personalised Medicine

www.oup.com
The following material is reproduced with kind permission of Nature Publishing Group
Figure 5 Continuum Mechanics and Its Practical Applications at the Level of Scaling Laws
Figure 2 Multi-scale Bone Mechanobiology
Figure 3 Multi-scale Bone Mechanobiology
Figure 5 Functional Magnetic Resonance Imaging
Figure 6 Functional Magnetic Resonance Imaging
Figure 4b Cell Mechanics and Cell Adhesion - Basic Principles and Computational Modeling
Figure 9 Diffusion Tensor Imaging
Figure 8 Corrosion of Biomaterials
Figure 8 Biomaterials for Tissue Engineering and Regenerative Medicine
Figure 3c Nanotechnology for Regenerative Engineering
Figure 4a Nanotechnology for Regenerative Engineering
Figure 4b Nanotechnology for Regenerative Engineering
Figure 6 Nanotechnology for Regenerative Engineering
i
ii Permission Acknowledgments

Figure 5 Drug and Gene Delivery for Regenerative Engineering
Figure 3 Holographic Microscopy
Figure 4 Radiomics
http://www.nature.com
BIOMATERIALS: SCIENCE AND ENGINEERING
Alternative Processing Techniques for CoCr Dental Alloys

Lucien Reclaru, VVSA, branch of Richemont International SA Varinor Innovation, Delémont, Switzerland
Lavinia Cosmina Ardelean, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania
© 2019 Elsevier Inc. All rights reserved.
Introduction 1
Manufacturing Technologies for CoCr Alloys 2
Evaluation of CoCr Alloys Manufactured by Different Technologies 5
Chemical Composition of the Alloys 5
Metallographical Evaluation 5
Corrosion Evaluation 8
Toxicological Aspects 13
Conclusions 15
References 15
Relevant Websites 15
Glossary
Castability The ease of forming a quality casting.
Electrochemical corrosion testing A process for studying various forms of metallic corrosion, which provides information
about the extent of corrosion activity.
Polarization curve Plot of current density versus electrode potential for a specific electrode-electrolyte combination.
Potentiodynamic polarization Probably the most commonly used polarization testing method for measuring corrosion
resistance; a technique where the potential of the electrode is varied at a selected rate by application of a current through the
electrolyte.
Sintering The process of compacting and forming a solid mass of material using heat or pressure without melting it.
Introduction
Since the early 1900s, a wide range of metals and their alloys are used in surgically implanted medical devices, prostheses and dental
materials, in order to provide improved physical and chemical properties, such as strength, durability and corrosion resistance
(Ardelean et al., 2015).
The classes of metals used in medical devices and dental materials include stainless steels, cobalt–chromium alloys, and titanium
(as alloys and unalloyed) (Wassell et al., 2002).
In addition, dental casting alloys are based on precious metals (gold, platinum, palladium, and silver), nickel, and copper and
may in some cases contain smaller amounts of many other elements, added to improve castability, handling, ceramic bond, or other
physical properties. Alloys used in dental applications classify as shown in Table 1.
Despite the wide range of dental alloys, each one of them has its shortcomings. Due to a number of factors, the use of CoCr based
alloys increased for the last years. Noble alloys became too expensive for the average population. Cobalt alloys are considered an
economic alternative to nonprecious nickel-based alloys, known as potential allergens. After a period of time when manufacturers
tried to produce better dental alloys, for example, CoCr based alloys doped with precious metals, which were quite a disappoint-
ment (Ardelean et al., 2015, 2010, 2016a), today the trend changed to improving the manufacturing process, as an alternative, and
not developing new compositions of the dental alloys. CoCr based alloys are known to have excellent corrosion resistance. Because
of their outstanding mechanical properties (e.g., high stiffness) these alloys are mainly used for the fabrication of removable partial
dentures, but also for metal-ceramic fixed dentures, where fine frameworks constructions are needed (Ardelean et al., 2015, 2016a).
Unfortunately, they are difficult to treat and to process for the dental technician and for the dentist in traditional casting technique
because of high hardness. Handling has considerably improved by using the new technologies which appeared in the last years, 3D
printing being considered as the “next industrial revolution.” In our “high-speed” and “low-cost” world these effortless and time
economically technologies, suitable for manufacturing the cheap CoCr alloys seem to be the best alternative available.
Encyclopedia of Biomedical Engineering, Volume 1 https://doi.org/10.1016/B978-0-12-801238-3.11100-6 1

2 Biomaterials: Science and Engineering j Alternative Processing Techniques for CoCr Dental Alloys
Table 1 Classification of dental alloys
Precious alloys Nonprecious alloys
Conventional crown and bridge alloys Nickel-based

High gold Type A-Base Ni–Cr, major secondary element: Be
Low gold Type B-Base Ni–Cr, major secondary element: Fe
Ag-based Type C-Base Ni–Cr, major secondary element: Mo
Alloys for the porcelain-fused-to metal technique Type D-Base Ni–Cr, major secondary element: Mn
High gold Type E-Base Ni–Cr–Fe
Low gold (NIOM Type B) CoCr-based, modified CoCr þ Pt, Ru, Nb, Au, In, Fe-CoCr
Pd-based: Pd Ag, Pd Sn, Pd Cu, Pd Cr, Pd Co Cu-based (bronze)
Titanium: Ti grade 1-4 , Ti-6Al-4V, Ti-6Al-7Nb, Ti- Mo, Ti-40Zr, Ti-Pd-Co, Ti-50Ni,
Ti-42.5Ni-7.5Pd, Ti-5Al-13Ta, Ti-5Ag, Ti-20Ag
Manufacturing Technologies for CoCr Alloys
Manufacturing technologies currently available for CoCr alloys are:

a. Traditional casting process (origin: bulk metal)
This traditional laborious and time consuming method implies castability problems and porosities which often appear when
specific flowing parameters of the casting machine are not respected.
b. Milling process (origin: bulk metal)
CAD/CAM technology implies obtaining a virtual image of the dental prosthesis based on an impression or a 3D image. The CAD
software virtually designs the prosthetic element and the milling unit physically manufactures it (Fig. 1). Milling CoCr blanks
(Fig. 2) may be difficult because its hardness and high demands are placed on the manufacturing unit (coolant delivery, rigidity
of the machine etc.) (Ardelean et al., 2016b).
A great progress was made by using milling units with four or five axes. In case of these milling units, the kinematics of the
machine is optimized, with large angulations of the fourth and fifth axes, more than 30 degrees. Thus it allows the milling and
the dry or wet grinding of very good quality dental prosthesis.
On the other hand, the elements obtained by milling do not show any structure defects such as porosities, cracks etc. (Fig. 3).
c. CAD/CAM sintering (origin: powder)
This is a new technology developed by Amann Girrbach, which uses nonprecious metal blanks with a wax-like texture and allows
them to be effortlessly dry milled in system’s benchtop machines. The milling is done in the green body state (unsintered metal
powder held together by a binder). These dry millable CrCr blanks are similar to partially sintered zirconia blanks and can be easily
processed in the preliminary state. After the required frameworks have been milled from the blank they are debinded and densely
sintered in a downstream process. The sintering process of the milled CoCr structures is easy carried out in a special furnace and
apparently gives a result with good structure quality: homogeneous, distortion-free frameworks without contraction cavities
(www.amanngirrbach.com).
d. 3D Printing Technologies (origin: powder)
In principle these technologies are very much alike, the differences come mainly in the process itself. 3D printers seamlessly inte-
grate with computer-assisted design (CAD) software and other digital files like magnetic resonance imaging.
Fig. 1 Milling of prosthetic elements according to CAD files.

Biomaterials: Science and Engineering j Alternative Processing Techniques for CoCr Dental Alloys 3
Fig. 2 CoCr blank for milling.
Fig. 3 CoCr prosthetic elements obtained by milling.
When talking about CoCr alloys manufacturing by 3D Printing, some alternatives are available:
• Selective laser sintering (SLS), developed by Dr. Carl Deckard in Austin USA.
In the mid-1980’s Deckard uses a moving laser beam to trace and selectively sinter powdered materials (including metals) into
successive cross-sections of a three-dimensional part. Selective laser sintering (SLS) technique uses a high power laser (CO2 laser)
to fuse small particles of metal powders into a mass representing a desired 3D object.
Based on a virtual image, the various powders (CoCr, NiCr or ceramic) are slowly built, layer by layer, as the 3D CAD software
measures thousands of cross-sections of each prosthetic element to determine exactly how each layer is to be constructed.
As in all rapid prototyping processes, the parts are built upon a platform that adjusts in height equal to the thickness of the layer
being built. After each cross-section is scanned, the powder bed is lowered by one layer thickness. Additional powder is deposited on
top of each solidified layer and sintered. The powder is maintained at an elevated temperature so that it fuses easily upon exposure
to the laser (www.popular3dprinters.com).
The laser selectively fuses metal powders by scanning cross-sections generated from a 3D digital description of the part, a CAD
file or scan data on the surface of a powder bed (Figs. 4 and 5) (Ardelean et al., 2016a; Reclaru et al., 2012a).
The laser sintering technique makes possible the manufacture of extremely accurate prosthetic elements with mechanical prop-
erties that correspond to any clinical requirement (Fig. 6).
• Direct metal laser sintering (DMLS), developed jointly by Rapid Product Innovations (RPI) and EOS GmbH in Munich,
Germany.
Starting in 1994, is the first commercial rapid prototyping method to produce metal parts in a single process. Metal powder, free of
binder or fluxing agent, is completely melted by the scanning of a high power laser beam to build the part with properties of the
original material. The absence of the polymer binder avoids the burn-off and infiltration steps, and results in a 95% dense steel part
compared to roughly 70% density in case of SLS. In addition DMLS has higher detail resolution than SLS, because of thinner layers,
enabled by a smaller powder diameter (www.popular3dprinters.com).
Fig. 4 3D digital description of the computer-based program for a fabrication tray.
Fig. 5 The laser selectively fuses the CoCr metal powder.
Fig. 6 Laser sintered prosthetic elements.
• Selective laser melting (SLM), started at the Fraunhofer Institute ILT in Aachen, Germany.
It is an additive manufacturing method that uses high powered laser to melt metallic powders together to shape the product from
a 3D CAD data. Renishaw uses a high powered ytterbium fiber laser to fuse metal powders (www.renishaw.com/en/metal-3d-
printing-for-healthcare). The recoater sweeps a layer of fine material powder and makes it ready for the laser to fuse them according
to the 2D cross section of each layer under a tightly controlled inert atmosphere. When the part is made completely, it goes for the
required heat treatment and postprocessing (www.popular3dprinters.com).
• Electron beam melting (EBM), developed by ARCAM AB in Sweden-General Electric-2016.

This is another type of additive manufacturing for metal parts, often classified as a rapid manufacturing method. The technology
manufactures parts by melting metal powder layer by layer with an electron beam in a high vacuum. Unlike some metal sintering
techniques, the parts are fully dense, void-free, and extremely strong (www.popular3dprinters.com).
Biomaterials: Science and Engineering j Alternative Processing Techniques for CoCr Dental Alloys 5
Evaluation of CoCr Alloys Manufactured by Different Technologies

Chemical Composition of the Alloys
The chemical composition of the CoCr alloys is shown in Table 2 (compositions as given by the manufacturers).
When comparing chemical composition, CoCr alloys for casting, milling, CAD/CAM sinter process and SLS do not show great
differences.
In addition, the Ceramill Sintron alloy blanks contain an organic binder. Ceramill Sintron sinter alloy has comparable and, in
the case of some parameters, even superior strength properties than cast CoCr. Similar evaluations are available in case of laser-
melted alloys compared with cast CoCr alloys (Geis-Gerstorfer et al., 2013).
Metallographical Evaluation
The CoCr samples were embedded in a cold-curing resin on a methyl methacrylate basis (Technovit, Kulzer), then polished with SiC
paper (grit 320/500/1200/1400) and finally with diamond spray (6/3/1 mm) (Struers). Electrolytic etching has been done in a bath
of 100 mL H2O dest., 10 mL HCl conc. and 5 g chromium (VI)-oxide during 5 s under 0.4 V and 0.3 A. The microstructures of the
alloys were observed using a metallographical microscope (Polyvar Met, Reichert-Jung). Two scanning electron microscopes (JEOL
JSM 6300) equipped with an EDX system (Oxford, INCA) for local phase analysis and SEM Sigma Zeiss with an Oxford X-MAX EDX
Instrument) for microanalysis were used. The analyzed samples were covered with a gold flash.
a. Traditional casting process (origin: bulk metal)
The use of CoCr alloys is traditionally carried out by casting, which is quite an unwieldy process. The cast structure is a classical
dendritic one (Fig. 7).
b. Milling process (origin: bulk metal)
Figs. 8–10 show the micrographical structures of the CoCr alloy without and with chemical attack. These are specific CoCr alloy
gross flow structures, obtained either by continuous casting of molten metal, or by hot lamination and cut into a disc form. There
are no abnormalities to be noticed.
The chemical composition of the phases is given in Table 3.
c. CAD/CAM sintering process (origin: powder)
The micrographical structure without chemical attack shows micrometric porosities, homogeneously distributed in sections. No
significant defects may be seen (Fig. 11).
Table 2 Composition of the alloys (wt.%)
Element Cast Milled Ceramill Sintron SLS
Co 63.7 60 66 64.1
Cr 28.9 24 28 29.3
Mo 5.3 4.5 5 4.9
Mn 0.8 <1 <1
Si <1 <1
W 0.1 8.5
Fe 0.4 <1
Fig. 7 Metallographic observation of a cast CoCr alloy.

Fig. 8 Micrographical structure of the CoCr alloy without chemical attack.
Fig. 9 SEM observation of the CoCr alloy without chemical attack.
Fig. 10 Micrographical structure of the CoCr alloy after chemical attack.
Table 3 The chemical composition of the phases
Spectrum C O Al Si Cr Mn Fe Co Mo Total
Spectrum 1: matrix 0.85 28.45 0.85 64.46 5.38 100.00

Spectrum 2: white phase 1.07 38.61 0.38 35.48 24.46 100.00
Spectrum 3: inclusion 14.37 37.13 0.47 17.74 12.26 1.18 14.72 2.13 100.00
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an unanswerable argument against him. I can scarcely, however, at
this moment forget how disconcerted I felt when he replied, “That is
nothing: I certainly never heard of Christians eating dead horse-
flesh, but I know they eat the flesh of swine, and God knows that is
worse!” “Grant me patience!” exclaimed I to myself; “this is almost
too much to bear, and to be silent.”
I endeavoured, by means of one of the Mandara people, to ask
some questions of some of these reputed Christians, but my
attempts were fruitless; they would hold no intercourse with any one;
and, on gaining permission, carried off the carcass of the horse to
the mountains, where, by the fires which blazed during the night, and
the yells that reached our ears, they no doubt held their savage and
brutal feast.
April 24.—The sultan of Mandara had given no intimation
whatever of his intentions with regard to Boo-Khaloom’s destination,
and in consequence the impatience and discontent of the latter were
extreme. Offerings poured in, from all the Kerdy nations; and the
sultan excused himself to Boo-Khaloom for the delay, on account of
the extreme tractability of the people around him, who, he said, were
becoming Musselmans without force. Again Musgow was
mentioned; adding, that the warlike arm of the Arabs, bearing the
sword of the Prophet, might turn their hearts. This hypocrisy,
however, Boo-Khaloom inveighed against most loudly to me,
declaring that the conversion of the Kerdy people would lose him
(the sultan) thousands of slaves, as their constant wars with each
other afford them the means of supplying him abundantly.
My own patience, also, this morning underwent a severe trial. I
applied to Barca Gana, by dawn of day, for one of his men to
accompany me to the mountains; and after some conversation a
chief was sent with me to the house of the suggamah (chief of the
town), who sent me to another, and he begged I might be taken to a
third. They all asked me a hundred questions, which was natural
enough; begged powder—looked at my gun—snapped the lock so
often, that I feared they would break it, exclaiming, “Y-e-o-o-o!
wonderful! wonderful!” when the fire came. At last, however, when I
once got it in my hand, I loaded both the barrels, and after that I
could not induce one of them to put their hands within five yards of it.
The last great man whose house I was taken to cunningly begged
me to fire, calling his slaves to stand round him while I complied with
his request: immediately after he asked for the gun, and carried it
into an inner court. I was kept full half an hour waiting; when about
ten slaves rushed out, gave me the gun, and told the guide to carry
me to the palace. I complained that they had stolen both my flints.
Every body came to look—crowded round me, exclaiming, “Y-e-o-o-
o!” and this was all the redress I could obtain. I soon after found out
that the flints were not my only loss; my pocket handkerchief also,
which several had petitioned for without success, had been stolen.
Arrived at the palace, I was desired to wait in the skiffa. I began to
walk about, but was told that was not allowed, that I must sit down
on the ground: after waiting nearly an hour, during which time I was
desirous more than once to return, but was told by my guide that it
was impossible until the sultan gave orders, I was conducted into the
presence of the chief eunuch; he desired me to stop within about
twelve yards of him, and then said, “The sultan could not imagine
what I wanted at the hills? Did I wish to catch the Kerdies alone?—
that I had better buy them,—he would sell me as many as I pleased.”
He then made some remark, which was not interpreted, and which
created a loud laugh in all the bystanders: the joke was evidently at
my expense, although I was not aware of its point. I assured him,
“that I did not wish to go at all to the hills if the sultan had the
slightest objection, that it was purely curiosity, and that as to catching
Kerdies, I would not take them if given to me.” This put us all to
rights; I gave him some powder, and he was as civil as he could be
to such a kafir as myself.
Six men, armed with large clubs and short daggers, were now
desired to go with me. The sultan’s anxiety for my safety, the eunuch
assured me, was the only reason I had found any difficulty. What
directions these, my satellites, had received, I know not, but they
watched me so closely, appeared so jealous of every stone I picked
up, that I did not venture to sketch the shape of a single hill. It was
now nearly mid-day, and we proceeded about three quarters of a
mile along the valley, which is on the south-west side of the town,
and advanced a little into two of the chasms, which appear in the
southernmost ridge of the chain. In one of these we found a beautiful
stream of water, bubbling from a bed of glittering sand, under two
immense blocks of granite, which seemed to form a rude arch over
the spot. Several naked people, chiefly women and girls, ran from
the place as we approached, and scrambled up the side of the
mountain with the most monkey-like agility. I was abundantly
assured that this chain of mountains, the highest parts of which, in
the neighbourhood of Mandara, do not exceed two thousand five
hundred feet, extends nearly south for more than two months’
journey—how much beyond that they know not. The only
communication, in this direction, is by means of a few venturesome
freed slaves, who penetrate into these countries with beads and
tobes, which are eagerly bought up, as well as turkadies from
Soudan, and slaves and skins are given in exchange. The nations
are very numerous; generally paint, and stain their bodies of different
colours, and live in common, without any regard to relationship.
Large lakes are frequently met with, plentifully supplied with fish.
Mangoes, wild figs, and ground nuts, are found in the valleys. It does
not appear that any other metal besides iron, which is abundant, has
been discovered in these hills: near Karowa, to the south-west of
Mandara, it is most plentiful.
The sound of the sultan’s trumpets, now heard at a distance,
created a strong sensation amongst my attendants; they all declared
we must return instantly; and when I very gently attempted to
remonstrate a little, one of them took hold of the reins of my horse
without any ceremony, turned him round, and led him on, while all
the rest followed towards the town; of course I very quietly
submitted, wondering what was the cause of alarm: it was, however,
nothing but that the Sultan was giving audience, and these
gentlemen of the chamber did not choose to be absent. They left me
as soon as we approached the houses, and I was then instantly
surrounded by at least a hundred others, who were so anxious to put
their hands into, and examine, every thing about me, that I put spurs
to my horse, and made the best of my way to the camp. I was
exceedingly fatigued with my morning’s work, and crept into my tent,
where I endured three hours of misery from a degree of excessive
heat, surpassing all I could have supposed mankind were born to
suffer here below.
Barca Gana sent to me soon after, and I found him preparing to
receive one of the chief eunuchs of the sultan in his outward tent; his
people all sitting round him on the sand, with their backs towards
their chief, and eyes inclined downwards. Nothing can be more
solemn than these interviews; not an eye is raised, or a smile seen,
or a word spoken, beyond “Long life to you! A happy old age!
Blessing! Blessing! May you trample on your enemies! Please God!
Please God!” then the fatah, which is seldom or never omitted. The
great man first inquired, “why I went to the hills; and what I wanted
with the stones I had picked up, and put in a bag which I carried near
my saddle?” Barca Gana applied to me for information, and the bag
was sent for. My specimens were not more than fifteen in number,
and the eunuch, laying his hand on two pieces of fine grained
granite, and some quartz, asked, “how many dollars they would bring
in my country?” I smiled, and told him, “Not one: that I had no object
in taking them beyond curiosity—that we had as much in England as
would cover his whole country, and that I was pleased to find similar
natural productions here. Assure the sultan,” added I, to Barca
Gana, “that to take any thing from any of the inhabitants of these
countries is not the wish of the English king: the sheikh knows our
intentions, which are rather to make them acquainted with European
produce; and if useful to them, send more into their country.” “True,
true!” said Barca Gana: “what have you brought for the sultan?”—
and here I was again in a dilemma. I had only one small looking-
glass of my own; neither knives, scissors, nor beads, although we
had cases of them at Bornou. Something, however, was necessary
to be given; I therefore sent for my trunk, and gave the sultan two
French red imitation shawls, which I had bought for my own use, my
own razor, and a pair of scissors; while for himself the eunuch took
my two remaining pocket-handkerchiefs, and a coloured muslin one,
with which he appeared to be highly delighted.
From a Sketch by Major Denham. Engraved by E. Finden.
MANDARA MUSICIANS.
Published Feb. 1826, by John Murray, London.
April 25.—The news of the presents I had produced brought early

this morning fifteen of the sultan’s sons, with double the number of
followers, to my tent: they all wanted gunpowder, knives, and
scissors; I had however neither one nor the other to give them. Two
or three of the oldest of the princes got a French silk handkerchief
each, and one a pair of cotton socks, and, of course, the others went
away sadly discontented. I this morning ventured to make two
attempts at sketching, but my apparatus and myself were carried off
without ceremony to the sultan. My pencils marking without ink,
created great astonishment, and the facility with which its traces
were effaced by India rubber seemed still more astonishing. My old
antagonist, Malem Chadily, was there, and affected to treat me with
great complaisance: he talked a great deal about me and my
country, which made his hearers repeatedly cry out, “Y-e-o-o-o!” but
what the purport of his observations were I could not make out. I
endeavoured, however, to forget all his former rudeness, took every
thing in good part, and appeared quite upon as good terms with him
as he evidently wished to appear to be with me. Several words were
written both by him and the others, which the rubber left no remains
of; at length the fighi wrote Bismillah arachmani aracheme (in the
name of the great and most merciful God), in large Koran characters;
he made so deep an impression on the paper, that, after using the
Indian rubber, the words still appeared legible: “This will not quite
disappear,” said I. “No, no!” exclaimed the fighi, exulting; “they are
the words of God, delivered to our Prophet! I defy you to erase
them!” “Probably so,” said I; “then it will be in vain to try.” He showed
the paper to the sultan, and then around him, with great satisfaction;
they all exclaimed, “Y-e-o-o-o! La illah el Allah! Mohammed rassoul
Allah!”—cast looks at me expressive of mingled pity and contempt,
and I was well pleased when allowed to take my departure.
The whole of this scene was repeated to Barca Gana in his tent in
the evening, and they all exclaimed “Wonderful! Wonderful!” and as I
did not contradict any part of his account, the fighi thus addressed
me: “Rais, you have seen a miracle! I will show you hundreds,
performed alone by the words of the wonderful book! You have a
book also, you say, but it must be false.—Why? Because it says
nothing of Saidna Mohammed, that is enough.—Shed! Shed! turn!
turn! say ‘God is God, and Mohammed is his prophet.’ Sully (wash),
and become clean, and paradise is open to you: without this, what
can save you from eternal fire? Nothing!—Oh! I shall see you while
sitting in the third heaven, in the midst of the flames, crying out to
your friend Barca Gana and myself, ‘Malem, saherbi! (friend), give
me a drink or a drop of water!’ but the gulf will be between us, and
then it will be too late.” The Malem’s tears flowed in abundance
during this harangue, and every body appeared affected by his
eloquence.
I felt myself, at this period, extremely uncomfortable; and Barca
Gana, who saw my distress, called me into the inner tent, where
nobody accompanied him, except by invitation. “The fighi,” said he,
“is a rajal alem (clever man).” “Very likely,” said I; “but he surely
might leave me to my own belief, as I leave him to his.” “Staffer
Allah!” (God forbid!) said he. “Do not compare them.” “I do not,” said
I, “God knows; but you, Kashella, should protect me from such
repeated annoyances.” “No,” replied Barca, “in this I cannot interfere.
Malem is a holy man. Please God! you will be enlightened, and I
know the sheikh wishes it; he likes you, and would you stay amongst
us, he would give you fifty slaves of great beauty, build you a house
like his son’s, and give you wives from the families of any of his
subjects you choose!” “Were you to return to England with me,
Kashella, as you sometimes talk about, with the sheikh’s permission,
would it not be disgraceful for you to turn Christian, and remain?
Were I to do as you would have me, how should I answer to my
sultan who sent me?” “God forbid!” said he; “you are comparing our
faiths again. I propose to you eternal paradise, while you would bring
me to ——.” “Not a word more,” said I.—“Good night!” “Peace be
with you! I hope we shall always be friends,” said he. “Please God!”
returned I. “Amen!” said the kashella.
This night we had a more dreadful storm than I ever remember
being out in. The top of my Egyptian tent, which I had preferred
bringing on account of its portability, was carried completely off, and
the pole broken. The brightness of the lightning rendered it more like
noon than midnight: a tamarind-tree was torn up by its roots in the
valley near us; huge masses of stone rolled down the sides of the
mountain; and I crept into a corner of Barca Gana’s outer tent, where
slept his guard; and, although every rag about me was drenched
with water, I was in a short time insensible to the storm which raged
around me.
In the morning, however, I suffered considerably from pains in all
my limbs and head. The Arabs, also, were full of complaints, and
extremely dissatisfied with their situation; they loudly exclaimed
against their delay. They had, for days, eaten nothing but a little flour
and water, without fat: the sultan of Mandara would grant them no
supply, and they demanded of Boo-Khaloom to go on, or turn back.
The rain again fell in torrents, which is an Arab’s greatest dread, and
they assembled round Boo-Khaloom’s tent, almost in a state of
mutiny. Boo-Khaloom himself was excessively ill, more, I believe,
from vexation than sickness. He had a long interview with the sultan,
and returned very much irritated: he merely told me, as he passed,
“that we should move in the evening;” and when I asked, “if every
thing went well?” he merely answered, “In shallah!” (please God).
The Arabs, from whom he kept his destination a secret, received him
with cheers. Whom they were going against they cared but little, so
long as there was a prospect of plunder, and the whole camp
became a busy scene of preparation.
Two hours after noon we commenced our march through a
beautiful valley to the east of Mora, winding round the hills which
overhang the town, and penetrating into the heart of the mass of
mountains nearly to the south of it. About sunset we halted in a very
picturesque spot, called Hairey, surrounded by a superb
amphitheatre of hills. Barca Gana’s tent was pitched under the
shade of one side of an immense tree, called gubberah, much
resembling a fig-tree, although wanting its delicious fruit; and the
remnants of my tent, which had been mended by his people, and
now stood about three feet from the ground, were placed on the
opposite side. The trunks of these trees commonly measure ten and
twelve yards in circumference near the root, and I have seen them
covering more than half an acre of ground with their wide-spreading
branches.
Pass of Hairy in the Mandara Mountains.
D. Denham. J. & C. Walker Sculp.
(Large-size)
Published as the Act directs Feby. 1826, by John Murray Albemarle St. London.
Soon after our arrival, the sultan’s trumpets announced his

approach, and he took up his station, at no great distance, under a
tree of the same kind: he never used a tent, but slept in an open
space, surrounded by his eunuchs. At Hairey are the remains of a
Mandara town, long since destroyed by the Felatahs; parts of the
mud walls were still standing, and under shelter of these the troops
bivouacked. The scorpions, however, made their appearance in the
course of the night in great numbers, and several men were stung by
them: on hearing the disturbance, and learning the cause, I called
my negro, and, striking a light, we killed three in my tent; one of them
was full six inches in length, of the black kind, exactly resembling
those I had seen in Tripoli.
In consequence of Boo-Khaloom’s illness, it was after daylight
when we broke up from our encampment, and probably the
mountain scenery, by which we were surrounded, could scarcely be
exceeded in beauty and richness. On all sides the apparently
interminable chain of hills closed upon our view: in rugged
magnificence, and gigantic grandeur, though not to be compared
with the Higher Alps, the Apennines, the Jura, or even the Sierra
Morena, in magnitude, yet by none of these were they surpassed in
picturesque interest. The lofty peaks of Vahmy, Savah, Joggiday,
Munday, Vayah, Moyung, and Memay, with clustering villages on
their stony sides, appeared to the east and west of us; while Horza,
exceeding any of her sister hills in height, as well as in beauty,
appeared before us to the south, with its chasm or break through
which we were to pass; and the winding rugged path we were about
to tread was discernible in the distance. The valley in which I stood
had an elevation superior to that of any part of the kingdom of
Bornou, for we had gradually ascended ever since quitting Kouka; it
was in shape resembling a large pentagon, and conveyed strongly
the idea of its having been the bed or basin of some ancient lake, for
the disappearance of which all hypothesis would be vain and
useless. There were the marks of many outlets, some long and
narrow fissures, through which the waters might have broken; the
channel by which we had entered appearing most likely to have
carried off its contents.
On proceeding through the pass of Horza, where the ascent
continued, its perpendicular sides exceeding two thousand five
hundred feet in height, hung over our heads with a projection almost
frightful; the width of the valley did not exceed five hundred yards,
and the salient and re-entering angles so perfectly corresponded,
that one could almost imagine, if a similar convulsion of nature to
that which separated were to bring its sides again together, they
would unite, and leave no traces of their ever having been disjoined.
It was long after mid-day when we came to the mountain stream
called Mikwa, and it afforded an indescribable relief to our almost
famished horses and ourselves: the road, after quitting the Horza
pass, had been through an extensive and thickly-planted valley,
where the tree gubberah, the tamarind, a gigantic wild fig, and the
mangoe (called by the Mandaras ungerengera, and comonah by the
Bornouese), flourished in great numbers and beauty. This was the
first spot I had seen in Africa where Nature seemed at all to have
revelled in giving life to the vegetable kingdom; the leaves presented
a bright luxuriant verdure, and flowers, from a profusion of climbing
parasitical plants, winding round the trunks of the trees, left the
imagination in doubt as to which of them the fair aromatic blossoms
that perfumed the air were indebted for their nourishment. The
ground had frequent irregularities; and broken masses of granite, ten
and twelve feet in height, were lying in several places, but nearly
obscured by the thick underwood growing round them, and by the
trees, which had sprung up out of their crevices. The nearest part of
the hills, to which these blocks could have originally belonged, was
distant nearly two miles.
When the animals had drunk we again moved on, and after
eighteen miles of equally verdant country, more thickly wooded, we
came, after sunset, to another stream, near some low hills, called
Makkeray, where we were to halt for a few hours to refresh, and then
move again, so as to commence an attack on the Felatahs, who
were said to be only about sixteen miles distant, with the morning
sun.
Our supper, this night, which indeed was also our breakfast,
consisted of a little parched corn pounded and mixed with water, the
only food we had seen since leaving Mora. Nothing could look more
like fighting than the preparations of these Bornou warriors, although
nothing could well be more unlike it than the proof they gave on the
morrow. The closely-linked iron jackets of the chiefs were all put on,
and the sound of their clumsy and ill-shapen hammers, heard at
intervals during the night, told the employment of the greater part of
their followers.
About midnight the signal was given to advance. The moon, which
was in her third quarter, afforded us a clear and beautiful light, while
we moved on silently, and in good order, the sultan of Mandara’s
force marching in parallel columns to our own, and on our right. At
dawn, the whole army halted to sully: my own faith also taught me a
morning prayer, as well as that of a Musselman, though but too often
neglected.
As the day broke on the morning of the 28th of April, a most
interesting scene presented itself. The sultan of Mandara was close
on our flank, mounted on a very beautiful cream-coloured horse, with
several large red marks about him, and followed by his six favourite
eunuchs, and thirty of his sons, all being finely dressed, and
mounted on really superb horses; besides which, they had each from
five to six others, led by as many negroes: the sultan had at least
twelve. Barca Gana’s people all wore their red scarfs, or bornouses,
over their steel jackets, and the whole had a very fine effect. I took
my position at his right hand, and at a spot called Duggur we entered
a very thick wood, in two columns, at the end of which it was said we
were to find the enemy.
During the latter part of the night, while riding on in front with
Maramy, the sheikh’s negro, who had accompanied me from Kouka,
and who appeared to attach himself more closely to me as we
approached danger, we had started several animals of the leopard
species, who ran from us so swiftly, twisting their long tails in the air,
as to prevent our getting near them. We, however, now started one
of a larger kind, which Maramy assured me was so satiated with the
blood of a negro, whose carcass we found lying in the wood, that he
would be easily killed. I rode up to the spot just as a Shouaa had
planted the first spear in him, which passed through the neck, a little
above the shoulder, and came down between the animal’s legs; he
rolled over, broke the spear, and bounded off with the lower half in
his body. Another Shouaa galloped up within two arms’ length, and
thrust a second through his loins; and the savage animal, with a
woful howl, was in the act of springing on his pursuer, when an Arab
shot him through the head with a ball, which killed him on the spot. It
was a male panther (zazerma) of a very large size, and measured,
from the point of the tail to the nose, eight feet two inches; the skin
was yellow, and beautifully marked with orbicular spots on the upper
part of the body, while underneath, and at the throat, the spots were
oblong and irregular, intermixed with white. These animals are found
in great numbers in the woods bordering on Mandara: there are also
leopards, the skins of which I saw, but not in great numbers. The
panthers are as insidious as they are cruel; they will not attack any
thing that is likely to make resistance, but have been known to watch
a child for hours, while near the protection of huts or people. It will
often spring on a grown person, male or female, while carrying a
burthen, but always from behind: the flesh of a child or of a young kid
it will sometimes devour, but when any full-grown animal falls a prey
to its ferocity, it sucks the blood alone.
A range of minor hills, of more recent formation than the granite
chain from which they emanate (which I cannot but suppose to form
a part of El Gibel Gumhr, or Mountains of the Moon), approaches
quite to the skirts of the extensive wood through which we were
passing; and numerous deep ravines, and dry water-courses,
rendered the passage tedious and difficult. On emerging from the
wood, the large Felatah town of Dirkulla was perceivable, and the
Arabs were formed in front, headed by Boo-Khaloom: they were
flanked on each side by a large body of cavalry; and, as they moved
on, shouting the Arab war-cry, which is very inspiring, I thought I
could perceive a smile pass between Barca Gana and his chiefs, at
Boo-Khaloom’s expense. Dirkulla was quickly burnt, and another
smaller town near it; and the few inhabitants that were found in them,
who were chiefly infants, and aged persons unable to escape, were
put to death without mercy, or thrown into the flames.
We now came to a third town, in a situation capable of being
defended against assailants ten times as numerous as the besieged:
this town was called Musfeia. It was built on a rising ground between
two low hills at the base of others, forming part of the mass of the
Mandara mountains: a dry wadey extended along the front; beyond
the wadey a swamp; between this and the wood the road was
crossed by a deep ravine, which was not passable for more than two
or three horses at a time. The Felatahs had carried a very strong
fence of palisades, well pointed, and fastened together with thongs
of raw hide, six feet in height, from one hill to the other, and had
placed their bowmen behind the palisades, and on the rising ground,
with the wadey before them; their horse were all under cover of the
hills and the town:—this was a strong position. The Arabs, however,
moved on with great gallantry, without any support or co-operation
from the Bornou or Mandara troops, and notwithstanding the
showers of arrows, some poisoned, which were poured on them
from behind the palisades, Boo-Khaloom, with his handful of Arabs,
carried them in about half an hour, and dashed on, driving the
Felatahs up the sides of the hills. The women were every where
seen supplying their protectors with fresh arrows during this struggle;
and when they retreated to the hills, still shooting on their pursuers,
the women assisted by rolling down huge masses of the rock,
previously undermined for the purpose, which killed several of the
Arabs, and wounded others. Barca Gana, and about one hundred of
the Bornou spearmen, now supported Boo-Khaloom, and pierced
through and through some fifty unfortunates who were left wounded
near the stakes. I rode by his side as he pushed on quite into the
town, and a very desperate skirmish took place between Barca
Gana’s people and a small body of the Felatahs. These warriors
throw the spear with great dexterity; and three times I saw the man
transfixed to the earth who was dismounted for the purpose of firing
the town, and as often were those who rushed forward for that
purpose sacrificed for their temerity, by the Felatahs. Barca Gana,
whose muscular arm was almost gigantic, threw eight spears, which
all told, some of them at a distance of thirty or thirty-five yards, and
one particularly on a Felatah chief, who with his own hand had
brought four to the ground.
· · · · · · · · · · · · · · · · · ·“Incidet ictus,
Ingens ad terram duplicato poplite Turnus.”
Had either the Mandara or the sheikh’s troops now moved up boldly,
notwithstanding the defence these people made, and the
reinforcements which showed themselves to the south-west, they
must have carried the town with the heights overlooking it, along
which the Arabs were driving the Felatahs by the terror their
miserable guns excited; but, instead of this, they still kept on the
other side of the wadey, out of reach of the arrows.
From a Sketch by Major Denham. Engraved by E. Finden.
ATTACK ON MUSFEIA.
Published Feb. 1826, by John Murray, London.
The Felatahs seeing their backwardness, now made an attack in

their turn: the arrows fell so thick that there was no standing against
them, and the Arabs gave way. The Felatah horse now came on;
and had not the little band round Barca Gana, and Boo-Khaloom,
with a few of his mounted Arabs, given them a very spirited check,
not one of us would probably have lived to see the following day: as
it was, Barca Gana had three horses hit under him, two of which died
almost immediately, the arrows being poisoned, and poor Boo-
Khaloom’s horse and himself received their death-wounds by arrows
of the same description. My horse was badly wounded in the neck,
just above the shoulder, and in the near hind leg: an arrow had
struck me in the face as it passed, merely drawing the blood, and I
had two sticking in my bornouse. The Arabs had suffered terribly;
most of them had two or three wounds, and one dropped near me
with five sticking in his head alone: two of Boo-Khaloom’s slaves
were killed also, near his person.
No sooner did the Mandara and Bornou troops see the defeat of
the Arabs, than they, one and all, took to flight in the most dastardly
manner, without having once been exposed to the arrows of the
enemy, and in the utmost confusion. The sultan of Mandara led the
way, who was prepared to take advantage of whatever plunder the
success of the Arabs might throw in his way, but no less determined
to leave the field the moment the fortune of the day appeared to be
against them.
I now for the first time, as I saw Barca Gana on a fresh horse,
lamented my own folly in so exposing myself, badly prepared as I
was for accidents. If either of my horse’s wounds were from
poisoned arrows, I felt that nothing could save me: however there
was not much time for reflection; we instantly became a flying mass,
and plunged, in the greatest disorder, into that wood we had but a
few hours before moved through with order, and very different
feelings. I had got a little to the westward of Barca Gana, in the
confusion which took place on our passing the ravine which had
been left just in our rear, and where upwards of one hundred of the
Bornowy were speared by the Felatahs, and was following at a
round gallop the steps of one of the Mandara eunuchs, who, I
observed, kept a good look out, his head being constantly turned
over his left shoulder, with a face expressive of the greatest dismay
—when the cries behind, of the Felatah horse pursuing, made us
both quicken our paces. The spur, however, had the effect of
incapacitating my beast altogether, as the arrow, I found afterwards,
had reached the shoulder-bone, and in passing over some rough
ground, he stumbled and fell. Almost before I was on my legs, the
Felatahs were upon me; I had, however, kept hold of the bridle, and
seizing a pistol from the holsters, I presented it at two of these
ferocious savages, who were pressing me with their spears: they
instantly went off; but another who came on me more boldly, just as I
was endeavouring to mount, received the contents somewhere in his
left shoulder, and again I was enabled to place my foot in the stirrup.
Remounted, I again pushed my retreat; I had not, however,
proceeded many hundred yards, when my horse again came down,
with such violence as to throw me against a tree at a considerable
distance; and alarmed at the horses behind him, he quickly got up
and escaped, leaving me on foot and unarmed.
The eunuch and his four followers were here butchered, after a
very slight resistance, and stripped within a few yards of me: their
cries were dreadful; and even now the feelings of that moment are
fresh in my memory: my hopes of life were too faint to deserve the
name. I was almost instantly surrounded, and incapable of making
the least resistance, as I was unarmed—was as speedily stripped,
and whilst attempting first to save my shirt and then my trowsers, I
was thrown on the ground. My pursuers made several thrusts at me
with their spears, that badly wounded my hands in two places, and
slightly my body, just under my ribs on the right side: indeed, I saw
nothing before me but the same cruel death I had seen unmercifully
inflicted on the few who had fallen into the power of those who now
had possession of me; and they were alone prevented from
murdering me, in the first instance, I am persuaded, by the fear of
injuring the value of my clothes, which appeared to them a rich booty
—but it was otherwise ordained.
My shirt was now absolutely torn off my back, and I was left
perfectly naked. When my plunderers began to quarrel for the spoil,
the idea of escape came like lightning across my mind, and without a
moment’s hesitation or reflection I crept under the belly of the horse
nearest me, and started as fast as my legs could carry me for the
thickest part of the wood: two of the Felatahs followed, and I ran on
to the eastward, knowing that our stragglers would be in that
direction, but still almost as much afraid of friends as foes. My
pursuers gained on me, for the prickly underwood not only
obstructed my passage, but tore my flesh miserably; and the delight
with which I saw a mountain-stream gliding along at the bottom of a
deep ravine cannot be imagined. My strength had almost left me,
and I seized the young branches issuing from the stump of a large
tree which overhung the ravine, for the purpose of letting myself
down into the water, as the sides were precipitous, when, under my
hand, as the branch yielded to the weight of my body, a large liffa,
the worst kind of serpent this country produces, rose from its coil, as
if in the very act of striking. I was horror-struck, and deprived for a
moment of all recollection—the branch slipped from my hand, and I
tumbled headlong into the water beneath; this shock, however,
revived me, and with three strokes of my arms I reached the
opposite bank, which, with difficulty, I crawled up; and then, for the
first time, felt myself safe from my pursuers.
Scarcely had I audibly congratulated myself on my escape, when
the forlorn and wretched situation in which I was, without even a rag
to cover me, flashed with all its force upon my imagination. I was
perfectly collected, though fully alive to all the danger to which my
state exposed me, and had already begun to plan my night’s rest, in
the top of one of the tamarind-trees, in order to escape the panthers
which, as I had seen, abounded in these woods, when the idea of
the liffas, almost as numerous, and equally to be dreaded, excited a
shudder of despair.
I now saw horsemen through the trees, still farther to the east,
and determined on reaching them, if possible, whether friends or
enemies; and the feelings of gratitude and joy with which I
recognised Barca Gana and Boo-Khaloom, with about six Arabs,
although they also were pressed closely by a party of the Felatahs,
was beyond description. The guns and pistols of the Arab sheikhs
kept the Felatahs in check, and assisted in some measure the
retreat of the footmen. I hailed them with all my might; but the noise
and confusion which prevailed, from the cries of those who were
falling under the Felatah spears, the cheers of the Arabs rallying and
their enemies pursuing, would have drowned all attempts to make
myself heard, had not Maramy, the sheikh’s negro, seen and known
me at a distance. To this man I was indebted for my second escape;
riding up to me, he assisted me to mount behind him, while the
arrows whistled over our heads, and we then galloped off to the rear
as fast as his wounded horse could carry us: after we had gone a
mile or two, and the pursuit had something cooled, in consequence
of all the baggage having been abandoned to the enemy, Boo-
Khaloom rode up to me, and desired one of the Arabs to cover me
with a bornouse. This was a most welcome relief, for the burning sun
had already begun to blister my neck and back, and gave me the
greatest pain. Shortly after, the effects of the poisoned wound in his
foot caused our excellent friend to breathe his last: Maramy
exclaimed, “Look, look! Boo-Khaloom is dead!” I turned my head,
almost as great an exertion as I was capable of, and saw him drop
from the horse into the arms of his favourite Arab—he never spoke
after. They said he had only swooned; there was no water, however,
to revive him; and about an hour after, when we came to Makkeray,
he was past the reach of restoratives.
About the time Boo-Khaloom dropped, Barca Gana ordered a
slave to bring me a horse, from which he had just dismounted, being
the third that had been wounded under him in the course of the day;
his wound was in the chest. Maramy cried, “Sidi rais! do not mount
him; he will die!” In a moment, for only a moment was given me, I
decided on remaining with Maramy. Two Arabs, panting with fatigue,
then seized the bridle, mounted, and pressed their retreat: in less
than half an hour he fell to rise no more, and both the Arabs were
butchered before they could recover themselves. Had we not now
arrived at the water as we did, I do not think it possible that I could
have supported the thirst by which I was consuming. I tried several
times to speak in reply to Maramy’s directions to hold tight, when we
came to breaks or inequalities in the ground; but it was impossible;
and a painful straining at the stomach and throat was the only effect
produced by the effort.
On coming to the stream, the horses, with blood gushing from
their nostrils, rushed into the shallow water, and, letting myself down
from behind Maramy, I knelt down amongst them, and seemed to
imbibe new life by the copious draughts of the muddy beverage
which I swallowed. Of what followed I have no recollection: Maramy
told me afterwards that I staggered across the stream, which was not

Encyclopedia of Biomedical Engineering Vol 1 3 Min Wang Full Chapter

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Encyclopedia of Biomedical

Engineering (vol. 1-3) Min Wang

Amsterdam • Boston • Heidelberg • London • New York • Oxford

Copyright Ó 2019 Elsevier Inc. All rights reserved.

Library of Congress Cataloging-in-Publication Data

British Library Cataloguing-in-Publication Data

For information on all publications visit our website

Publisher: Oliver Walter

Printed and bound in the United States

Diego Mantovani, Ph.D., FBSE.

Tyler Ackley M Bohner

Tzahi Cohen-Karni Margaret A T Freeberg

Natalia Davidenko Vincenzo Guarino

Xingyu Jiang Dimitrios A Lamprou

Stefani Mazzitelli David A Puleo

Swaminathan Sethuraman Mian Wang

Biomaterials: Science and Engineering

Natural Biopolymers for Biomedical Applications 162

Biomaterials: In Vitro and in Vivo Studies of Biomaterials

Biomaterials: Biomaterial Applications and Advanced Medical Technologies

Microﬂuidics for Biomedical Applications 368

Human Parthenogenetic Pluripotent Stem Cells 608

Porous Biomaterials and Scaffolds for Tissue Engineering 188

Biomaterials: In Vitro and in Vivo Studies of Biomaterials

Biomaterials: Biomaterial Applications and Advanced Medical Technologies

Shape-Memory Polymer Medical Devices 394

Introduction to Regenerative Engineering 624

Mathematical Quantiﬁcation of the Impact of Microstructure on the Various Effective

Iron-Based Degradable Implants 374

Magnetic Resonance Imaging 574

Rehabilitation Engineering and Integrative Technologies

Mathematical Techniques in Biomedical Engineering

Single-Cell-Based In Silico Models: A Tool for Dissecting Tumor Heterogeneity 130

Bioinstrumentation and Bioinformatics

Machine Learning in Biomedical Informatics 389

Roger J Narayan, M.D., Ph.D.

Figure 1 On the Use of Population-Based Statistical Models in Biomechanics

Figure 8a Nanotechnology for Regenerative Engineering

Figure 1 Translational Bioinformatics for Personalised Medicine

Figure 7c Nanotechnology for Regenerative Engineering

Alternative Processing Techniques for CoCr Dental Alloys

Encyclopedia of Biomedical Engineering, Volume 1 https://doi.org/10.1016/B978-0-12-801238-3.11100-6 1

Table 1 Classiﬁcation of dental alloys

Precious alloys Nonprecious alloys

Conventional crown and bridge alloys Nickel-based

Manufacturing Technologies for CoCr Alloys

Manufacturing technologies currently available for CoCr alloys are:

Fig. 1 Milling of prosthetic elements according to CAD ﬁles.

Fig. 2 CoCr blank for milling.

Fig. 3 CoCr prosthetic elements obtained by milling.

Fig. 4 3D digital description of the computer-based program for a fabrication tray.

Fig. 5 The laser selectively fuses the CoCr metal powder.

Fig. 6 Laser sintered prosthetic elements.

• Electron beam melting (EBM), developed by ARCAM AB in Sweden-General Electric-2016.

Evaluation of CoCr Alloys Manufactured by Different Technologies

Table 2 Composition of the alloys (wt.%)

Element Cast Milled Ceramill Sintron SLS

Fig. 7 Metallographic observation of a cast CoCr alloy.

Fig. 8 Micrographical structure of the CoCr alloy without chemical attack.

Fig. 9 SEM observation of the CoCr alloy without chemical attack.

Fig. 10 Micrographical structure of the CoCr alloy after chemical attack.

Table 3 The chemical composition of the phases

Spectrum 1: matrix 0.85 28.45 0.85 64.46 5.38 100.00