Biomedical Engineering Reference
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layer on crystals of the poorly crystalline phase of biological apatite.
Although there has been no direct evidence for this possibility, similar
coatings appear to form in physiological-like solutions seeded with
HA [257, 258]. Under these
conditions, the initial accretions
appeared to form an amorphous calcium carbonate-ACP coating on
the seed crystals. The initial phase also incorporated a small amount
of Mg
in vitro
2+
ions from solution that was subsequently released upon the
ancillary formation of CDHA crystals. This Mg
behavior, consistent
with the amorphous-to-crystalline transition, is the most compelling
compositional evidence from these studies for the initial coat being
an amorphous layer [257].
A proper assessment of the possibility that some of the mineral
in skeletal tissues is in a free-standing amorphous state is further
complicated by the fact that the minimum ion activity product
needed to form ACP
2+
in physiological-like synthetic solutions
at pH 7.4 is considerably greater than that calculated for serum [126,
259]. If extracellular skeletal fluids were in electrolyte equilibrium
with serum, it would appear unlikely that ACPs could form
de novo
in vivo
except possibly as a coating on crystals of biological apatite of
bones. Without stronger evidence than that described above, even
this possibility, though, is highly speculative. However, there is
some evidence that suggests that calcifying bone matrix may be
compartmentalized with the establishment of an interior milieu
different from that of serum [260]. Unfortunately, it is not known
whether such compartmentalization results in an extracellular fluid
space capable of initiating
ACP formation [20].
Although the general compartmentalization of bone-producing
conditions favorable for ACP needs to be further established,
a considerable body of evidence suggests that local micro-
compartments exist in bones that could allow for ACP development.
The most thoroughly studied of these micro-spaces are the
membrane-enclosed aqueous cores of matrix vesicles [261, 262].
Most commonly found near osteoblasts in the extracellular regions
of rapidly mineralizing embryonic bone, these spherical bodies of
cellular origin are the sites of initial mineral formation [263]. Preceding
appearance of the first crystals at these sites is an accumulation of
calcium and orthophosphate ions within the aqueous cores of the
vesicles to levels that far exceed the threshold level for
de novo
ACP
formation [264, 265]. Studies with synthetic liposomes confirm that
ACP should readily form under such compartmentalized conditions
de novo
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