Natural bone is a composite material composed of organic compounds (mainly collagen) reinforced with inorganic compounds (minerals). Apparently, the single mineral phase of bone is too brittle and easy to break while the single collagen phase is too soft and does not have mechanical stability (such as compression strength). The composite chemistry of bone provides both strength and resilience so that the skeleton can absorb energy when stressed without breaking. The detailed composition of bone differs depending on species, age, dietary history, health status, and anatomical location. In general, however, the inorganic phase accounts for about 70% of the dry weight of bone, and the organic matrix makes up the remainder (Buckwalter et al. 2000).
The inorganic or mineral component of bone is primarily rod-like (20-80 nm long and 2-5 nm in diameter) crystalline hydroxyapatite, Ca10(PO4)6(OH)2 or HA. Small amounts of impurities, which affect cellular functions, may be present in the mineralized HA matrix; for example, magnesium, strontium, sodium, or potassium ions may replace calcium ions, carbonate may replace phosphate groups, whereas chloride and fluoride may replace hydroxyl groups. Because the release of ions from the mineral phase of the bone matrix controls cell-mediated functions, the presence of impurities may alter certain physical properties of bone (such as solubility) and consequently important biological aspects, which are critical to normal bone function. For example, magnesium present in the mineralized matrix may enhance cellular activity and promote the growth of HA crystals and subsequent new bone formation (Buckwalter et al. 2000).
Approximately 90% of the organic phase of bone is Type I collagen; the remaining 10% consists of noncollagenous proteins and ground substances. Type I collagen found in bone is synthesized by osteoblasts and is secreted as triple helical procollagen into the extracellular matrix (ECM), where collagen molecules are stabilized by cross-linking of reactive aldehydes among the collagen chains. Generally, each of the 12 types of collagen found in the body consists of three polypeptide chains composed of approximately 1,000 amino acids each. Specifically, Type I collagen (molecular weight 139,000 Da) possesses two identical a1(I) chains and one unique a2 chain; this configuration produces a fairly rigid linear molecule that is 300 nm long. The linear molecules (or fibers) of Type I collagen are grouped into triple helix bundles having a periodicity of 67 nm, with gaps (called hole-zones)
between the ends of the molecules and pores between the sides of parallel molecules (Vigier et al. 2010; Zhu et al. 2005; Miyahara et al. 1984). The collagen fibers provide the framework and architecture of bone, with the HA particles located between the fibers. Noncollagenous proteins, for example, growth factors and cytokines (such as insulin-like growth factors and osteogenic proteins), bone inductive proteins (such as osteonectin, osteopontin, and osteocalcin), and ECM compounds (such as bone sialoprotein, bone proteoglycans, and other phospho-proteins as well as proteolipids), provide minor contributions to the overall weight of bone but provide large contributions to its biological functions. During new bone formation, noncollagenous proteins are synthesized by osteoblasts, and mineral ions (such as calcium and phosphate) are deposited into the hole-zones and pores of the collagen matrix to promote HA crystal growth. The ground substance is formed from proteins, polysaccharides, and mucopolysaccharides which acts as a cement, filling the spaces between collagen fibers and HA crystals.
It is not only the complex physiochemical properties of natural bone that make it difficult to replace, but also its dynamic ability. Bone has the capability of self-repair under excessive mechanical stresses by activating the remodeling process through the formation of a bone-modeling unit (BMU). Although the inorganic and organic components of bone have structural and some regulatory functions, the principal regulators of bone metabolism are bone cells, including osteoblasts (bone-forming cells), osteocytes (bone-maintaining cells), and osteoclasts (bone-resorbing cells). Bone as a living organ can change in size, shape, composition, microstructure, and properties by its remodeling process throughout its lifetime to respond to different kinds of stress produced by physical activity or mechanical loads. The remodeling process involves the removal of old bone and regeneration of new bone at the same site.
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