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21 – Chapter 2: Background (Part II) Bone Heirarchical Levels

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2.1 Bone Structure and Hierarchy {1}

Bone is a composite material that exists on at least 5 hierarchical levels: whole bone, architecture, tissue, lamellar, and ultrastructural level (Figure 1). The whole bone is at the greatest scale and represents the overall shape of the bone. This structure is composed of the architectural level, which contains the microstructure that defines the spatial distribution. Below the architectural level is the tissue level, which is inherent to the actual material properties of bone. The lamellar, or cellular level is below the tissue level and is composed of sheets of collagen and minerals deposited by osteoblasts [1]. The minimal scale level is the ultrastructural level which incorporates chemical and quantum interactions [2]. These five levels comprise structural differences in size magnitude between the subsequent levels, spanning from the whole bone to the chemical and quantum level [3]. In order for the research community to expedite a full characterization of bone, each separate constituent that contributes to the system as a whole must be evaluated. There are certain advantages that can be gained by separating the structure into microstructural organizational levels. By viewing bone at different hierarchical levels it is easy to compare different structures and tissues. Additionally, it is much simpler to define characteristic levels to use for analysis. Each level depends on the levels below it to provide function and structural support (Table 1).

{1} This section adopted from Liebschner MA, Wettergreen MA “Optimization of Bone Scaffold Engineering for Load Bearing Applications.” In Ferretti P., Ashammakhi N.: Topics in Tissue Engineering, e-book on tissue engineering, T. Waris & N. Ashammakhi, Chapter 22,, 2003.

Whole Bone Level

The top level of bone is the organ level, or whole bone level, and it represents the summation of the structural and material properties of all the levels of bone. At this level, the bone functions on the order of magnitude of the organism, providing structural support and aiding with locomotion. The mechanical characteristics of whole bone are a result of the complete structure’s geometry (Figure 2). Interaction between whole bone and other constituents of the body may include tendons, ligaments, muscles and other bones.

Bone Heirarchical Levels
Figure 1. Illustration of structures corresponding to hierarchical levels of bone. [4].
Bone Heirarchical Levels
Table 1. Structural Hierarchy and Mechanical Properties of Bone [4].
Optimization at this level is not seen in a shape change, but as a net mass change resulting from external/internal factors. Shape changes are minimal and the mechanical strength of the structure is derived from the total geometry of the bone and the distribution of tissue. Remodeling that may occur at lower levels is measured as percent increase or decrease in mass in the overall bone [6].
Femur, Whole Bone
Figure 2. Example of Whole Bone Level. Human Femur [5].

Architectural Level

The architectural level of bone relates to the characteristic micro-architecture of bone tissue, specifically cortical or trabecular bone (Figure 3). These structures serve to provide mechanical stability to the global structure of bone distributed throughout the osteons and/or trabeculae. This is the first level at which the remodeling of the organism can be visualized as a change in architecture. Architectural reorganization also affects the apparent properties of the structure. Two different architectures arise depending on anatomical site and loading conditions. Trabecular bone, contained in the ends of long bones and the site of bone marrow synthesis, exhibits anisotropy as a result of its rod and plate organization. Cortical bone is highly compact and orthotropic due to the circular nature of the osteons that make up its

Figure 3. On left, SEM of trabecular bone illustrating thinning of the trabecular in the center forefront. On right, photomicrograph of cortical bone illustrating the individual osteons and osteocytes [7, 8].

structure. One illustration of the micro-architectural differences between the two architectures is that cortical bone contains only microscopic channels through the center of the osteons whereas trabecular bone is highly porous (Figure 3) [9]. Mechanical function at the architectural level is to provide support for the overall bone structure and, specifically in trabecular bone, to act as a shock absorber and resist compressive loads [10]. The mechanical strength can be related to several geometric constraints such as trabecular thickness, bone mineral density, and bone surface to bone volume ratio. These constraints can be obtained from imaging techniques used to evaluate trabecular tissue [11]. Strain sensed in the bones at this architectural level causes the cells on lower hierarchical levels to remodel the gross arrangement of the micro-architecture at the surface [12]. Although gross reorganization of the bone micro-architecture is seen at this level as a change in geometry and architecture, the deposition and resorption occurs at the cellular level. Orientation and mechanical qualities change between anatomical sites and between bones as a result of dynamic loading and stress on bone tissue. The mechanical characteristics of the architectural level are largely due to the spatial distribution of the tissue (micro-architecture) and less so due to the properties of the material composing bone. The remodeling at this stage does not take an ordered path and thus may look random, but the structure that results from it is anything but unordered. The rods and plates that compose the trabecular bone follow a pattern of resorption and deposition according to the mechanotransduction principles of the bone. Due to the complexity of the bone, previous models have attempted to approximate the bone as simpler solids, such as open-celled foams or tetrakaidecagons [13, 14]. This will be discussed later in the mathematical approximation of trabecular bone.

Tissue Level

Below the architectural level of bone is the tissue level, which directly addresses the mechanical properties of the tissue. The material properties at this level provide support for the geometry of the architectural level above it. Remodeling of bone at this stage of the hierarchy alters the material properties of the bone tissue. Tissue properties are those that relate directly to the mechanical characteristics of the bone independent of the micro-architecture. Properties such as stiffness, Young’s Modulus, yield point, and energy to fracture can be dealt with on a fundamental material level. The optimization that occurs at this level is as a result of the modification of the material properties, and is responsible for the apparent properties of the architectural level.
Lamellar Level

Figure 4. Illustration of Lamellae.

Below the tissue level of bone is the lamellar level (Figure 4); the layers of bone deposited by single cells. Lone structures, the lamellae are laid on top of each other like composite board in directions that vary by up to 90 degrees. These laminations are the lowest form of bone and are deposited by the basic multicellular unit (BMU). This process involves the recruitment of osteoclasts that resorb bone; osteoblasts are then recruited to deposit bone; the process ends with the encapsulation of the osteoblasts in the bone matrix before they differentiate into mechanosensing osteocytes; finally, the osteoblasts deposit a layer of hydroxyapatite onto a woven bed of collagen [9, 15]. The sheets of lamellae are on the order of 3-20µm in thickness [3]. It is this process that produces all of the lamellar bone (Figure 4) in the body, which is a much stronger and better form of bone than embryonic or woven bone. The deposition and resorption of bone occurs only at the surface, however, the lowest layers of lamellae are not affected unless massive bone loss is experienced, as in osteoporosis.

Ultrastructural Level

The lowest level of the bone hierarchy considered in this review is the ultrastructural level. At this level chemical and quantum effects can be addressed. The order of magnitude for this level allows the analysis of the mechanics and architecture of the collagen fibers with the minerals [2]. The ultrastructural level is on the order of calcium and other minerals that are a part of bone, such as phosphate and magnesium. The advantage of viewing bone at this level is that it allows the study of an additional function of bone that cannot be addressed until this size. This function is the use of bone as mineral storage for the organism. Mineral storage and the effects of chemistry are the main functional points at the ultrastructural level as is the orientation of collagen in the lamellae [1]. The design of bone at this level illustrates how the micro-architecture of the structure must be evaluated as well as the nano-architecture. Several studies have been completed on the difference in ultrastructural mechanical properties as a result of the collagen orientation and the amount of mineral deposition on the collagen beds. The degree of mineralization will affect the final stiffness of the bone itself as well as the overall ash content [3].

1. Majeska, R., Cell Biology of Bone, in Bone Biomechanics Handbook, S.C. Cowin, Editor. 2001, CRC Press LLC: Boca Raton. p. (2)1-(2)-24.
2. van der Linden, J.C., et al., Trabecular bone’s mechanical properties are affected by its non-uniform mineral distribution. J Biomech, 2001. 34(12): p. 1573-80.
3. Lucchinetti, E., Composite Models of Bone Properties, in Bone Biomechanics Handbook, S.C. Cowin, Editor. 2001, CRC Press LLC: Boca Raton. p. (12)1-(12)19.
4. Liebschner, M.A.K. and M.A. Wettergreen, Optimization of Bone Scaffold
Engineering for Load Bearing
Applications, in Topics In Tissue Engineering, N. Ashammakhi and P. Ferretti, Editors. 2003.
5. Wikipedia. Femur. 2008 [cited; Available from:
6. Yaszemski, M.J., et al., Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials, 1996. 17(2): p. 175-85.
7. Blue Histology. 2003 [cited 2003 12.2]; Available from:
8. Hollister, S.J. Bone Structure. 2003 [cited 2003 12.2]; Available from:
9. Jee, W., Integrated Bone Tissue Physiology: Anatomy and Physiology, in Bone Biomechanics Handbook, S.C. Cowin, Editor. 2001, CRC Press LLC: Boca Raton. p. (1)1-(1)68.
10. Borah, B., et al., Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis. Anat Rec, 2001. 265(2): p. 101-10.
11. Kopperdahl, D.L. and T.M. Keaveny, Yield strain behavior of trabecular bone. J Biomech, 1998. 31(7): p. 601-8.
12. Smith, T.S., et al., Surface remodeling of trabecular bone using a tissue level model. J Orthop Res, 1997. 15(4): p. 593-600.
13. Gibson, L.J. and M.F. Ashby, Cellular Solids: Structure and Properties. 1988, New York: Pergamon Press. 357.
14. Pearce, P., Structure in nature is a strategy for design. 1990, Cambridge, Massachusetts: MIT Press. 245.
15. Sikavitsas, V.I., J.S. Temenoff, and A.G. Mikos, Biomaterials and bone mechanotransduction. Biomaterials, 2001. 22(19): p. 2581-93.


Written by Matthew Wettergreen

March 26, 2008 at 9:33 am

Posted in thesis

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