ADDITIVE MANUFACTURING FOR BONE LOAD BEARING APPLICATIONS - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 225

scaffold morphology (pore size, shape, and interconnectivity), transient biochemical interactions, and
mechanical properties ( Bohner et al., 2011; Butscher et al., 2011 ).
11.2 COMPOSITIONAL, STRUCTURAL AND MECHANICAL
PROPERTIES OF BONE
11.2.1 COMPOSITIONAL PROPERTIES OF BONE AND REQUIREMENTS
FOR BONE SUBSTITUTES
Bone is a dynamic and complex organ, encompassing a variety of tissues such as mineralized osse-
ous tissue, cartilage, endosteum, periosteum, marrow, nerves, and blood vessels ( Porter et al., 2009 ).
The main role of the bone network is in providing the necessary mechanical support, movement,
and protection, with other roles ranging from blood production, to storage of mineral materials, pH
regulation, and housing multi progenitor cells ( Porter et al., 2009; Szpalski et al., 2012 ). Due to the
complex nature of the bone as biological system, in the context of fabricating bone substitute implants,
the focus is generally on understanding the biochemical and structural makeup of the bone extracel-
lular matrix (ECM), as well as the interaction of the ECM with cells and the environment in which
they reside ( Szpalski et al., 2012 ). The bone ECM is in essence a composite material comprised of
carbonated apatite ( ∼ 69% of the ECM), mainly hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) crystals, entrapped
in an organic matrix ( ∼ 22% of the ECM) of mostly type I collagen, and water ( ∼ 9 % of the ECM)
( Szpalski et al., 2012; Bose and Tarafder, 2012 ). Lipids, proteins, and osteogenic factors also reside
in the ECM organic matrix ( Bose and Tarafder, 2012 ). From a compositional point of view, the bone
substitute matrix should be at least biocompatible with the ECM, cellular, and chemical environment,
osteoconductive to encourage fast bone ingrowth from surrounding healthy tissue ( Pilliar et al., 2001 ),
as well as nontoxic, nonmutagenic, noncarcinogenic, and nonteratogenic ( Leong et al., 2003 ). Ideally,
the material should be osteoinductive to promote formation of new bone at the site ( Porter et al., 2009;
Yang et al., 2001 ).
11.2.2 STRUCTURAL PROPERTIES OF BONE AND REQUIREMENTS
FOR BONE SUBSTITUTES
Structurally, the bone ECM is comprised of two main zones with very different morphological proper-
ties. Trabecular bone, also known as cancellous bone, is a highly porous bone matrix, with intercon-
nected porosities between 50-90% and visible macropores in the range of 500-1000 m m ( Karageorgiou
and Kaplan, 2005 ). Trabecular bone has a complex and organized porous architecture, with trabeculae
following the direction of mechanical stress ( Porter et al., 2009 ) as a direct result of adaptations to
mechanical loading, as postulated by Wolff's law ( Bartel et al., 2006 ) and the mechanostat theory
( Frost 2003 ). Trabecular bone encloses bone marrow and is enclosed by cortical bone. Cortical bone
ECM has a compact solid-like structure, with enclosed vascular Haversian canals, having a low poros-
ity between 3-12%, and pores < 500 m m ( Karageorgiou and Kaplan, 2005 ). Cortical bone has a solid
structure with a series of voids, for example Haversian canals, with a 3-12% porosity (typical apparent
density values for proximal tibial trabecular bone 0.30 ± 0.10 g/cm3). The bone ECM is constantly
remodeled by the cells that reside in it, where osteoblasts are responsible for producing and mineral-
izing new bone matrix, osteocytes work on maintaining the matrix, and osteoclasts are responsible for