Bone Grafts And Bone Substitutes Basic Science And
Clinical Applications
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Contents
Preface ix
Introduction xi
A Nather
Contributors xiii
SECTION I: BASIC SCIENCE OF BONE
Chapter 1 Structure of Bone 3
A Nather, HJC Ong and Z Aziz
Chapter 2 Fracture Healing 19
A Nather, MCB Feng and ZAziz
Chapter 3 An Introduction to Biomechanics of Bone 31
B P Pereira and A Thambyah
SECTION II: AUTOGRAFTS
Chapter 4 Autogenous Bone Grafting in Orthopaedic Surgery 59
KL Pan and S Ibrahim
Chapter 5 Vascularised Pedicular Bone Grafts 71
PB Chacha
Chapter 6 Vascularised Autograft: Basic Sciences and 95
Clinical Applications
YK Rang and YG Chung
Chapter 7 Healing of Large, Non-Vascularised, Cortical
Autologus Bone Transplants: An Experimental
Study in Adult Cats 119
A Nather
v
vi • Contents
SECTION III: ALLOGRAFTS
Chapter 8 Role of Bone Allografts in Orthopaedic Surgery 139
A Nather and Z Aziz
Chapter 9 Setting Up a Tissue Bank 155
A Nather and LH Wang
Chapter 10 Quality Control Issues in Tissue Banking 173
NHilmy
Chapter 11 Is the Irradiation Dose of 25 kGy Enough to
Sterilise Tissue Grafts? 189
N Yusof
Chapter 12 Diploma Course Training of Tissue Bank
Operators: 7 Years of Experience 213
A Nather, WY Teo and LH Wang
Chapter 13 Healing of Large Diaphyseal Deep-Frozen
Cortical Allografts 227
A Nather
Chapter 14 Bone Allotransplantation: Future Directions 243
SM Kumta, PC Leung and LK Fu
SECTION IV: GENOMICS
Chapter 15 The Human Genome 257
5 Aziz, BC Lin and A Nather
Chapter 16 Genomics in Orthopaedics 269
A Nather, S Aziz and F Kagda
Chapter 17 Gene Therapy and New Bone Formation 277
LHC Tsai, SYENeo and A Nather
SECTION V: BONE TISSUE ENGINEERING
Chapter 18 Stem Cell Technology and its Commercial Potential 297
S Rauffand RE Oakley
Contents • vii
Chapter 19 Setting Up a Tissue Engineering Laboratory 313
A Nather, CW Lee and ZQ Tang
Chapter 20 Culturing Mesenchymal Stem Cells from Bone Marrow 321
A Nather, S Das De and CW Lee
Chapter 21 Bone Marrow Derived Mesenchymal Stem Cells:
Potential for Tissue Regeneration 335
J Rosocha, G Vasko, G Varga and D Harvanovd
Chapter 22 Scaffolds in Bone Tissue Engineering 357
A Nather and S Aziz
Chapter 23 Carriers of Mesenchymal Cells 367
A Nather and V David
SECTION VI: GROWTH FACTORS
Chapter 24 The Role of Bone Morphogenic Proteins in
Bone Incorporation 379
A Nather and A Dutton
Chapter 25 Platelet-Rich Plasma in Orthopaedic Surgery:
Basic Science and Clinical Applications 387
S Das De, R Manohara and A Nather
Chapter 26 Applications of Autogenous Platelet Rich
Plasma (PRP) Gel to Enhance Bone Formation 405
C-J Yim
SECTION VII: CERAMICS
Chapter 27 The Need for New Materials for Use in Bone in Man 431
PA Revell, E Damien
Chapter 28 Role of Ceramics as Bone Graft Substitutes 445
V David, A Nather and KA Khalid
Chapter 29 Enhancement of the Bioactivity of Orthopaedic
Biomaterials: Role of Growth Factors, Ion
Substitution and Implant Architecture 459
E Damien and PA Revell
viii • Contents
Chapter 30 Fabrication of Granular Hydroxyapatite 489
F Fazan
Chapter 31 Role of Corals and Coralline Ceramics in
Orthopaedic Surgery 501
V David, A Nather and KA Khalid
Chapter 32 Biomedical Use of Corals and Coralline
Hydroxyapatite in Hard Tissue Replacement 513
E Damien and PA Revell
Chapter 33 Coral as Bone Graft Substitute 533
SA Hamid, AR Samsudin, R Salim and N Omar
SECTION VIII: PROSTHESES
Chapter 34 Rapid Prototyping in Orthopaedics: Principles
and Applications 547
/ Abdullah and AY Hassan
Chapter 35 Custom Mega Prosthesis for Bone Reconstruction in
Orthopaedic Surgery 563
MV Natarajan, M Paraskumar and G Rajkumar
Index 591
Preface
This book discusses Bone Grafting using autografts from non-vascularised
grafts to pedicled ones and free vascularised bone grafts and the various
options to bone grafting ie. the use of bone substitutes. The latter ranges from
Allografts, Genomics in Orthopaedic Practice with particular reference to
Bone Formation, Tissue Engineering including all 3 elements of the triad —
Cells, Scaffolds and Signalling Molecules to Ceramics and Prostheses. The
section of Ceramics include some results from the ten million ringgit Multi-
Centre Research Project in Malaysia namely the fabrication of Malaysian
Hydroxyapatite and the development of Malaysian Coral.
This book is useful to clinicians and clinician scientists in the field
of Orthopaedics, Plastic and Reconstructive Surgery and Maxillo-Facial
Surgery who are commonly presented with the clinical problem of recon-
structing large bone defects. It is also useful to research scientists namely
tissue engineers and biomedical engineers pursuing the field of research on
bone substitutes in the field of allograft transplantation, genomics of bone,
bone tissue engineering and the development of new generation bioceramics
and new prostheses.
Associate Professor Aziz Nather
IX
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Introduction
A Nather
Bone Grafting is one of the commonest operations performed in Ortho-
paedics. Its indications include non-union, delayed union, packing bone
cysts and cavities, elevating depressed articular fractures and reconstruction
of large bone defects. Autografting from the iliac crest is the gold standard.
However, due to limitations as to amount, size and shape of the graft that
could be procured as well as associated donor site morbidity, bone substi-
tutes have become extremely important and useful for Orthopaedic Surgery,
Plastic Reconstructive Surgery and Maxillo-Facial Surgery.
Section I first addresses the Basic Science of Bone including the struc-
ture of bone and the biomechanics of bone and the repair process that occurs
in fracture healing.
Autografts are discussed in detail in Section II including the method
of performing autogenous bone grafting and its diverse clinical applica-
tions.The ipsilateral pedicled bone graft and also the free vascularised bone
graft are covered in detail. The healing of large non-vascularised cortical
bone transplants is also described.
Section n i deals with a common bone substitute — Allografts. Allo-
grafts have served this function very well for the last 5 decades. A useful
chapter especially for Universities who have not set up a tissue bank is the
chapter on "Setting Up a Tissue Bank" which serves as a useful guide to
all wishing to establish a new bone banking facility. Issues of quality con-
trol for allografts, value of gamma irradiation to sterilize the bone grafts
and the training of tissue bank operators are addressed in detail. Biology
xi
xii • Introduction
and biomechanics of healing of cortical allografts and the future of bone
allotransplantation is also described.
Section IV introduces the field of Genomics and discusses the use
of Genomics in Orthopaedic Practice with particular reference to bone
formation.
Bone Tissue Engineering is covered in depth in Section V including
methodology for culturing Mesenchymal Stem Cells, types of scaffolds
used and types of carriers employed for transplantation of cells.
In Section VI the third element of the Tissue Engineering Triad is
addressed, namely signalling Molecules or Growth Factors. The role of
BMPs and PRP are discussed.
Section VII covers Ceramics. Its scope ranges from the need of new
biomaterials to the role of Hydroxyapatite, Coral and Coralline Ceramics
as bone substitutes. The fabrication of the Malaysian Hydroxyapatite and
the Malaysian Coral recently developed are also described.
Finally, this book on Bone Graft Substitutes would not be complete
without discussing one other option, namely Prostheses. Rapid prototyp-
ing techniques and the use of Custom MegaProstheses are described in
Section VIII.
Contributors
Suzina Sheikah ABDUL HAMID P.B. CHACHA
Consultant, Ear, Nose and Throat Consultant Orthopaedic Surgeon
Department Mount Elizabeth Hospital
Malaysian National Tissue Bank 3 Mount Elizabeth
School of Medical Sciences, Universiti Singapore 228510
Sains Malaysia Health Campus
Kota Bharu, Kelantan, Malaysia
CHANG-Joon Yim, DDS
MSD, PhD
ENE Implant Center
Jamaluddin ABDULLAH Youngil Bldg. #201, Seochodong
School of Mechanical Engineering 1675-13, Seochoku
University of Sciences Malaysia — Seoul, 137-070, Republic of Korea
Engineering Campus
Seri Ampangan, 14300 Nibong Tebal
Seberang Perai Selatan, Penang, Yong Guk CHUNG
Malaysia Department of Orthopaedic Surgery
Catholic University Medical College
St. Vincent's Hospital
Sharnaz AZIZ Suwon, 440-060, Korea
Laboratory Technologist
Department of Orthopaedic Surgery Elsie DAMIEN
National University of Singapore Biomaterials and Tissue Engineering,
10 Kent Ridge Crescent Eastman Dental Institute, UCL,
Singapore 119260 LondonWClX8LD,UK
Zameer AZIZ Soumen DAS DE, MBBS
Laboratory Technologist Medical Officer
Department of Orthopaedic Surgery Department of Orthopaedic Surgery
National University of Singapore National University of Singapore
10 Kent Ridge Crescent 10 Kent Ridge Crescent
Singapore 119260 Singapore 119260
xiii
xiv • Contributors
Vikram DAVID, MBBS, MS (Orth) Ahmad Yusoff HASSAN
Medical Officer School of Mechanical Engineering
Department of Orthopaedic Surgery University of Sciences Malaysia —
National University Hospital Engineering Campus
5 Lower Kent Ridge Road Seri Ampangan, 14300 Nibong Tebal
Singapore 119074 Seberang Perai Selatan, Penang,
Malaysia
Andrew Quoc DUTTON, MBBS,
Nazly HILMY, PhD
FRCS (Ortho)
Batan Research Tissue Bank,
Registrar
Centre for Research and Development
Department of Orthopaedic Surgery
of Isotopes and Radiation Technology
National University Hospital
Batan, Jakarta
5 Lower Kent Ridge Road
Singapore 119074 Sharaf IBRAHIM, MD, FRCS, MS
(UKM)
Fazilah FAZAN Associate Professor and Paediatric
AMREC, SIRIM Berhad, Orthopaedic Surgeon
Lot 34, Jin Hi-Tech 2/3 Department of Orthopaedics
Kulim Hi-Tech Park, University Kebangsaan Malaysia
09000 Kulim, Kedah, Malaysia Kuala Lumpur, Malaysia
Fareed Hussain KAGDA, MBBS,
FENG Min Chin Bernard FRCS (Ortho)
Laboratory Technologist Consultant
Department of Orthopaedic Surgery Department of Orthopaedic Surgery
National University of Singapore National University Hospital
10 Kent Ridge Crescent 5 Lower Kent Ridge Road
Singapore 119260 Singapore 119074
L.K. FU, MBBS, MPhil Yang Koo KANG, MD, PhD
Professor
Department of Orthopaedics and
Department of Orthopaedic Surgery
Traumatology
Catholic University Medical College
The Chinese University of Hong Kong
St. Vincent's Hospital
Shatin NT, Hong Kong, China
Suwon, 440-060, Korea
Denisa HARVANOVA Kamarul Ariffin KHALID
Faculty of Medicine Lecturer
The Pavol Jozef Safarik University Department of Orthopaedic Surgery
and University Hospital International Islamic University of
Trieda SNP 1 Malaysia
040 66 Kosice, Slovak Republic Kuantan, Malaysia
Contributors • xv
Shekhar M KUMTA, MS (Orth), Mayil Vahanan NATARAJAN,
PhD MBBS, D Orth (Ma's), M Ch
Associate Professor Trauma Orth (Liverpool), PhD
Department of Orthopaedics and (Orth Onco)
Traumatology Professor
The Chinese University of Hong Kong Head, Department of Orthopaedic
Shatin NT, Hong Kong, China Surgery
Madras Medical College
Periyar EVR Salai
LEE Choon Wei Chris Park Town, Chennai
Laboratory Officer Tamil Nadu, India 600 003
Department of Orthopaedic Surgery
National University of Singapore Aziz NATHER, MBBS, FRCS (Ed),
10 Kent Ridge Crescent FRCS (Glas), AM, MD
Singapore 119260 Associate Professor
Department of Orthopaedic Surgery
National University of Singapore
P.C. LEUNG, FRCS, DSc 10 Kent Ridge Crescent
Department of Orthopaedics and Singapore 119260
Traumatology
The Chinese University of Hong Kong
SYE NEO
Shatin NT, Hong Kong, China
Department of Orthopaedic Surgery
National University Hospital
5 Lower Kent Ridge Road
LIN Bitong Clarabelle Singapore 119074
Laboratory Technologist
Department of Orthopaedic Surgery
National University of Singapore Reida El OAKLEY
10 Kent Ridge Crescent Associate Professor
Singapore 119260 Department of Surgery
National University of Singapore
10 Kent Ridge Crescent
Singapore 119074
Ruben MANOHARA, MBBS
Medical Officer
Department of Orthopaedic Surgery Nor Shamsuria OMAR
National University Hospital Malaysian National Tissue Bank
5 Lower Kent Ridge Road School of Medical Sciences, Universiti
Singapore 119074 Sains Malaysia Health Campus
Kota Bharu, Kelantan, Malaysia
xvi • Contributors
ONG Hui Jing Christine Peter A REVELL
Laboratory Technologist Biomaterials and Tissue Engineering,
Department of Orthopaedic Surgery Eastman Dental Institute, UCL,
National University of Singapore London WC1X8LD, UK
10 Kent Ridge Crescent
Singapore 119260 Jan ROSOCHA, DVM, CSc
Head of Associated Tissue Bank
Faculty of Medicine
PAN Kok Long The Pavol Jozef Safarik University
Professor and University Hospital
Head, Department of Orthopaedics Trieda SNP 1
University Malaysia Sarawak 040 66 Kosice, Slovak Republic
Kuching, Sarawak, Malaysia
Rosdan SALIM
Consultant, Ear, Nose and Throat
M. PARASKUMAR Department
Department of Orthopaedic Surgery
Malaysian National Tissue Bank
Madras Medical College
School of Medical Sciences, Universiti
Periyar EVR Salai
Sains Malaysia Health Campus
Park Town, Chennai
Kota Bharu, Kelantan, Malaysia
Tamil Nadu, India 600 003
Abdul Rani SAMSUDIN
Dean, Faculty of Dentistry
Barry PEREIRA, M. Eng
Research Fellow Director, Malaysian National Tissue
Bank
Department of Orthopaedic Surgery
National University Singapore School of Medical Sciences, Universiti
10 Kent Ridge Crescent Sains Malaysia Health Campus
Singapore 119260 Kota Bharu, Kelantan, Malaysia
TANG Zhi Qun
G. RAJKUMAR Laboratory Officer
Department of Orthopaedic Surgery Department of Orthopaedic Surgery
Madras Medical College National University of Singapore
Periyar EVR Salai 10 Kent Ridge Crescent
Park Town, Chennai Singapore 119260
Tamil Nadu, India 600 003
TEO Wan Yee
Laboratory Technologist
Shanaz RAUFF Department of Orthopaedic Surgery
University of Pennsylvania National University of Singapore
13-15 Lermit Road 10 Kent Ridge Crescent
Singapore 258646 Singapore 119260
Contributors • xvii
Ashvin THAMBYAH, M.Eng, M.Sc Gabriel VASKO, MD, CSc
Research Fellow Associate Professor
Department of Orthopaedic Surgery Faculty of Medicine
National University Singapore The Pavol Jozef Safarik University
10 Kent Ridge Crescent and University Hospital
Singapore 119260 Trieda SNP 1
040 66 Kosice
Slovak Republic
TSAI Hui Ching Larry, MBBS
WANG Li Hui
Medical Officer
Senior Laboratory Technologist
Department of Orthopaedic Surgery
NUH Tissue Bank
National University Hospital
National University Hospital
5 Lower Kent Ridge Road
5 Lower Kent Ridge Road
Singapore 119074
Singapore 119074
Norimah YUSOF, BSc, MSc, PhD
Gabriel VARGA Director of Agrotechnology &
Faculty of Medicine Biosciences Division
The Pavol Jozef Safarik University Malaysian Institute for Nuclear
and University Hospital Technology Research (Mint)
Trieda SNP 1 Bangi, 43000 Kajang
040 66 Kosice, Slovak Republic Selangor, Malaysia
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SECTION I
Basic Science of Bone
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