Stem Cell-Based Tissue Engineering for Bone Repair - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 2

The macro-scale structure of bone enables it to protect the internal organs, pro-
vide a support frame for the body, allow movement through the interactions with
muscles, as well as produce blood cells. In addition to these functions, the micro-
scale properties of bone allow it to regulate mineral storage, fat storage, and phos-
phate metabolism [ 1 ].
The mechanical properties and biological functions of bone are derived from
the cells, water, and the extracellular matrix proteins—chiefly, type-I colla-
gen [ 1 ]. The mineral component of the extracellular matrix, a form of calcium
phosphate called hydroxyapatite, gives bone its hardness, while type-I colla-
gen gives bone its flexibility. The ability of bone to remodel and repair itself
is due to the coordinated function of cells, along with the presence of bone
marrow. Bone marrow contains hematopoietic and non-hematopoietic stem
cells from which osteoclasts and osteoblasts respectively originate [ 1 ].
Engineering scaffolds that can incorporate these components to augment bone
healing is a key research area in bone tissue regeneration. Strategies that promote
endogenous or synthetic repair mechanisms have been investigated. It is currently
unknown which mechanism is optimal for engineered bone regeneration, although
a design mimicking endogenous repair seems to be the most promising [ 2 ].
2 Bone Formation and Healing
2.1 Fracture Healing
Fracture healing in long bones involves a series of events beginning with inflam-
mation, followed by formation of a hematoma (clot) surrounded by the periosteal
layer of bone. The repair process of the fracture site is organized by the structure
of the hematoma [ 3 ]. The structure of the hematoma provides a scaffold in which
rapid cell division can occur [ 3 ]. Within this scaffold, the possible sources of the
osteogenic cells involved in enabling fracture repair have been debated. One theory
suggests that the repair tissue arises from cells that are predetermined to differenti-
ate into bone, while the second theory asserts that the repair tissue is formed from
the activity of uncommitted cells that develop osteogenic potential given certain
environmental stimuli, a process termed “osteogenic induction” [ 3 ].
The first theory described above likely refers to mesenchymal stem cells that are
predetermined to an osteogenic fate, while the second theory describes cell types
that are similar to pluripotent embryonic stem cells [ 3 , 4 ]. With regards to the first
theory, it is well known that during bone formation, osteoblasts are recruited from
mesenchymal stem cells in the bone marrow, while osteoclasts are formed from
hematopoietic stem cells predetermined to a monocyte lineage [ 3 ]. It has also been