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CHAPTER 1
Title
A.Author, B.Author2
1
Affiliations
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Abstract
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from the Introduction.
Keywords
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Section Headings
1. Introduction ......................................................................................................
2. Basics of Bone Biology .....................................................................................
References ...............................................................................................................
1.
INTRODUCTION
Skeletal tissue regeneration is a subject of intensive research in orthopedics, because
skeletal defects, especially bone defects, acutely influence quality and length of human
life. Bone is a complex and a highly specialized form of connective tissue pertaining
to the formation of the skeleton of the body. It is a good example of a dynamic tissue
in the human body since it has a unique capability of strong regenerative potential
throughout the life without leaving a scar. However, skeletal defects resulting from
trauma, tumor, or bone abnormality often call for bone grafting procedures. Each year,
millions of people suffer from bone defects and several die due to insufficiency of
ideal bone graft and/or failure of implanted bone regenerative system. With reference
to statistical reports [1-3], about 6.3 million fractures occur every year in the United
States of America (USA) itself, of which about 550,000 cases require some kind of
bone grafting. It was also noticed that the fractures occur at an annual rate of 2.4 per
100 populations. The most frequently occurring fractures are, in decreasing order, hip,
ankle, tibia, and fibula fractures. It is reported that the total number of hip
replacements was about 152,000 in the year of 2000, which is an increase of about
33% compared to the year of 1990 in the USA alone and it is expected to increase to
about 272,000 by the year of 2030 [4], indicating that there is a great need for synthetic
bone grafts. According to a reported data [5], bone graft sales was found to exceed
US$980 million in 2001 in the USA and about US$1.16 billion in 2002, which is also
expected to double by 2006.
2.
2.1
BASICS OF BONE BIOLOGY
COMPONENTS OF BONE TISSUE
The design strategy of biomimetic bone grafts is not straightforward without
understanding at least the rudiments of bone composition, structure, and the way in
which it is organized. Bone is a well-organized connective tissue made of several
building blocks at multiple levels, from nano to macro, that consist of, in decreasing
proportions, minerals, collagen, water, non-collagenous proteins, lipids, vascular
elements, and cellular components. An overall composition of the bone is given in
Table 1 [6]. Bone, in general, is composed of approximately 70% of minerals and 30%
of proteins. The bone minerals are chiefly enriched with nanophase HA and the bone
proteins mainly consist of collagen nanofibers. Collagen acts as a structural
framework in which nanocrystals of HA is embedded to strengthen the bone tissue.
The bone collagen has a typical fibrous structure, whose diameter varies from 100 to
2000 nm. Similarly, HA in the bone mineral is in the form of plate-like nanocrystals
with dimensions of about 4 nm by 50 nm by 50 nm. The bone minerals are also
enriched with few trace elements for various metabolic functions, which include
carbonate, citrate, sodium, magnesium, fluoride, chloride, potassium, and iron. The
Chapter title
prime role of minerals is to provide toughness and rigidity to the bone, whereas
collagen provides tensile strength and flexibility. It is really amazing to know, how the
nature built extremely hard and tough bone using such soft (collagen) and brittle (HA)
ingredients. Bone, not only provides mechanical support for the organism but also
elegantly serves as a reservoir for minerals, particularly calcium and phosphate. A
complete biological mechanism involved in the bone building strategy is still unclear
and thus research progresses still in this direction. It is believed that the key to the
strength of the bone is the complex structural hierarchy into which it is organized in a
self-assembling mode. It is important to note that the minerals are not directly bound
to collagen, but bound through non-collagenous proteins. The process involved in this
strategy is often called as biological mineralization or biomineralization. The noncollagenous proteins make up approximately 3 to 5% of the bone, which provide active
sites for biomineralization.
Lipids are also play an important role during
biomineralization. It is worth stating that, in general, biomineralization typically begins
only 10 days after the organic matrix, particularly collagen, is laid-down. The key
mechanism involved in the biological mineralization is briefly discussed in Section 5.
Table 1. Composition of bone tissue [6].
Inorganic phase (wt.%)
Organic phase (wt.%)
Hydroxyapatite  60
Collagen  20
Carbonate
 4
Water
 9
Citrate
 0.9
Non-collagenous proteins  3
Sodium
 0.7
(osteocalcin, osteonectin, osteopontin,
Magnesium
 0.5
thrombospondin, morphogenetic proteins,
Other traces:
sialoprotein, serum proteins),
Cl-, F-, K+ Sr2+, Pb2+, Zn2+,
Other traces:
Cu2+, Fe2+
Polysaccharides, lipids, cytokines.
Primary bone cells:
osteoblasts, osteocytes, osteoclasts.
4
Chapter title
5
REFERENCES
[1]
A Praemer, S. Furner, D. P. Rice: Musculoskeletal conditions in the United
States (American academy of orthopaedic surgeons, Rosemont 1999).
[2]
American
academy
of
orthopedic
surgeons
http://www.aaos.org/wordhtml/research/stats/facts.htm.
(AAOS).
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