CHAPTER 1 Title A.Author, B.Author2 1 Affiliations email Abstract The abstract should be short and approx. 100 words. It can be based on key sentences from the Introduction. Keywords Please list up to 5 keywords describing your chapter. 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).