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International Journal of Bioprinting 3D bone: Current & future

Table 1. Mechanical properties of bone tissues regulate their pathological functions and are also involved
in all stages of bone formation, including cell proliferation,
Material property Compact bone Spongy bone osteogenesis, mineral deposition, remodeling, and
Compressive strength 130–200 0.1–16 collagen fibrillogenesis. 14,15,17 Gla is an amino acid with a
(MPa) dicarboxylic acid side chain and is found in several forms
Tensile strength (MPa) 50–151 5–10 in the body with different functions (e.g., as blood clotting
Compressive modulus 11.5–17 0.12–1.1 factors and plasma proteins). Gla is located in bone and
(GPa) other mineralized tissues, such as osteocalcin (OCN),
Young’s modulus (GPa) 7–30 0.05–0.5 bone matrix Gla protein (MGP), and periostin. OCN
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Fracture toughness 2–12 0.1–0.2 binds to calcium and is stored in bones. It acts as a glucose
0.5
(MPa·m ) and energy metabolism regulator, and its increased serum
concentration stimulates bone formation. In addition,
responsible for producing the bone matrix, which plays a OCN is released into the blood through bone resorption
significant role in bone regeneration. As the ECM builds processes. Conversely, MGPs are responsible for inhibiting
around them and mineralizes, osteoblasts mature into bone mineralization, while periostin is an adhesion
osteocytes. Although osteocytes have reduced synthetic molecule that promotes osteoblast aggregation, adhesion,
activity and cannot undergo mitotic division (similar to proliferation, and differentiation, as well as collagen
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osteoblasts), they are actively involved in remodeling the fibrillogenesis. Glycoproteins, such as osteonectin,
bone matrix. Additionally, nodules of mineralization thrombospondins, and R-spondins, are composed of a
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of hydroxyapatite (HA), calcium carbonate, and protein chain and several different carbohydrate linkages
calcium phosphate mineralization are commonly found and are typically found in bone ECM. Osteonectin
surrounding the osteocytes. In contrast, osteoclasts are regulates calcium release by binding to HA crystals and
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phagocytotic cells of bone tissues and are responsible collagen fibers, and high concentrations of osteonectin
for removing degraded bone materials (i.e., erosion by can cause osteoporosis; thrombospondins are essential in
osteocytes). Osteoclasts are usually found on the surface of skeletal development, bone cell differentiation, and bone
the bone in cavities, called Howship lacunae. mass maintenance; R-spondins regulate embryonic bone
9,13
development and adult bone remodeling. SIBLINGs are
2.1.2. Bone extracellular matrix a family of glycoproteins and commonly include bone
The bone ECM is a unique composite material that contains sialoprotein (BSP), osteopontin (OPN), dentin matrix
approximately 65–70% inorganic minerals and 30–35% protein-1 (DMP1), dentin sialophosphoprotein (DSPP),
organic compounds (Table 2), the ratio of which varies and matrix extracellular phosphoglycoprotein (MEPE).
with age or physiological state. The main component BSP plays a vital role in the regulation of osteoblast
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of the inorganic phase is HA (Ca [PO ] [OH] ), which differentiation and the initiation of matrix mineralization,
3
10
4 6
is made up of two mineral salts: calcium phosphate and while OPN, DMP1, and MEPE are involved in the
calcium hydroxide. In addition to these two components, regulation of matrix mineralization. In teeth, DSPP plays
trace elements (calcium, magnesium, fluorine, sodium, a similar role to BSP. Additionally, DMP1 and MEPE also
and sulfate) are often bound into the inorganic crystals. regulate the binding of phosphate to bones.
Calcification is a process whereby the inorganic crystals
are deposited around collagen fibrils. 2.2. Functions of bone tissues
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Bone tissues provide the skeletal framework that
In contrast, the organic phase is composed of protects the body. Additionally, bone tissues are a passive
approximately 90% type I collagen and 10% type III and V component of movement, function as a mineral store, and
collagen and non-collagen proteins. 14,15 Collagens are coiled play an essential role in hematopoiesis (protecting the red
into triple-stranded helices to form fibers, providing both a and yellow bone marrow during hematopoiesis). In the
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mechanically stable structure and a scaffold for bone cells. body, many organs (e.g., lungs, kidneys, liver, skin, and
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Likewise, the non-collagen proteins can be subdivided intestines) can serve as buffer systems to maintain an ideal
into four groups: γ-carboxyglutamic acid (Gla) proteins, pH of 7.2–7.4. Bones are also considered a buffer system,
proteoglycans, glycoproteins, and small integrin-binding owing to their phosphate storage. Besides that, bones
ligand N-linked glycoproteins (SIBLINGs). Proteoglycans can rapidly bind to and accumulate heavy metals and
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consist of polysaccharide fibers and proteins, and some subsequently release them in smaller doses for efficient
small leucine-rich proteoglycans (SLRP) play a crucial role removal. Therefore, bones can protect the other tissues
in bone tissue homeostasis and bone tissue formation. 15,16 from heavy metal poisoning by absorbing toxic metals in
Proteoglycans interact with cell surface receptors to the body. Notably, some heavy metals can also damage

Volume 10 Issue 3 (2024) 145 doi: 10.36922/ijb.2056