Biomedical Engineering Reference
In-Depth Information
With HAP, which forms bone tissue in the human body, a number of formation
theories were proposed many years ago. For example, Robinson theorized that
HAP nucleation occurs as a result of a localized increase in the phosphate ion
concentration due to hydrolysis of the organic phosphate ester substrate by the en-
zyme alkaline phosphatase [
43
]. Newman and Newman theorized that the molecular
chains on the collagen surfaces behave as effective sites of HAP nucleation [
1
].
Brighton and Hunt theorized which that once the fine HAP nuclei formed from
the calcium and phosphate ions in a matrix vesicle grow to a certain size, they break
through and arrange themselves on the collagen fibers [
44
]. Newman and Newman's
epitaxial theory leads to the contemporary notion of biomineralization. With the
matrix vesicle theory, the amount of HAP that can be formed in the bone is much
greater than the amount that can be formed in the matrix vesicles. In other words,
in addition to the HAP that is formed within the matrix vesicles, there is a need for
HAP formation to occur directly from the body fluids onto collagen fibers.
Each of these theories focuses on HAP nucleation. The growth and dissolution
behavior of HAP in formed bone tissue has led to a biological consensus on the
concept of remodeling [
45
]: the renewal over time of bone tissue occurs through the
growth and dissolution of HAP. It involves competition between osteoclasts, which
dissolve bone, and osteoblasts, which create bone.
3.4.3
Constant Composition Method
Consideration of HAP as a pure inorganic compound in an attempt to understand
its mechanisms of growth and dissolution physicochemically would not reveal the
essence of these mechanisms due to the complex systems—including cells—that are
involved. Even considering that various types of cells play a primary role in bone
tissue formation within the organism, the phenomenon that consequently occurs at
the interface between HAP and the environmental phase (body fluid) is ultimately
crystal growth of inorganic salts. Therefore, illustration of the HAP formation
mechanisms within the organism requires first conducting studies in simple cell-free
aqueous solution systems. Researchers investigating the HAP growth mechanisms
have mainly been doing this since the 1970s.
Early studies were done using Bennema's procedure: estimate the dependence of
the HAP growth rate on supersaturation and compare the data with growth theories
such as the BCF model to elucidate the growth mechanisms. In a growth experiment
using highly crystalline synthetic HAP polycrystals as seeds [
46
], the growth rate
and chemical composition of HAP were obtained by measuring the solution pH
as well as the calcium and phosphate ion concentrations accompanying growth.
The growth rate was estimated from the change in solution composition, which was
derived from HAP surface area. The growth rate data had a relationship of
R
2
,
and it was concluded that spiral growth, which could be expected in solutions with
low supersaturation, took place. Since the measurements were in a closed system,
the change in the chemical composition of the solution associated with HAP growth
would lead to a change in supersaturation. In addition, it could not be conclusively
