An essential component of the skeletal system is bone

An
essential component of the skeletal system is bone structure. The main features
of bone structure include providing body support, motion, and production. The
body’s bone structure serves many important functions of the human body. It
protects the body and is a location for the creation of specialized tissues
such as bone marrow, the body’s system that creates blood. Also, bone structure
plays a huge role in structurally supporting the mechanical action of the
body’s soft tissues. For example, the contraction of muscles to move or
expansion of lungs to breathe. Having a healthy bone structure has a
significant relevance to the body, as it also serves as a mineral reservoir,
where endocrine systems regulate the level of phosphate and calcium ions in the
body fluids that circulate in the body.

 In the smallest levels of cell observation,
bone is a highly complex and specialized form of connective tissue. Bone is a
mineralized tissue made out of an organic matrix that is strengthened by
accumulation of calcium phosphate compounds. In summary, this means that bone
is a natural composite material. The compositional make-up of the organic
matrix in bone consists of three main components. These three main components
include the following: approximately 95% collagen type I fibers, proteoglycans,
and many different types of non-collagenous proteins. The organic matrix in
bone is calcified by calcium phosphates minerals and works to embed bone cells.
These bone cells are called the osteoprogenitor cells and participate in the
maintenance of the bone structure and the organization of bone. They include
three types: osteoblasts, osteocytes, and osteoclasts.

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A
biomaterial is any non-pharmaceutical material that can be used to treat or
replace any tissue, organ, or function in an organism. Biomaterial research is
one of the most important fields of modern medicine used in organ transplant, wound
healings, drug delivery, and prosthetic replacements. The main focus of this
study is to investigate biomaterial, more specifically bioceramic, on
prosthetic enhancement or replacement. Certain characteristics of biomaterials
make them the preferred choice for medical applications, and these include the
following: they are biodegradable, biocompatible, and non-toxic. The different
classes of biomaterial include polymers, metals, ceramics (including carbons,
glass-ceramics, and glasses), and natural materials (both from plants and
animals) (Ige, Aribo, & Umoru, 2012).

When
a bioactive material is incorporated into the body’s structure, several
biological reactions occur at the implant-tissues interface that result in a
mechanically stable chemical interfacial bonding called bioactive fixation.
Also, several key requirements need to be fulfilled for successful use of
biomaterials, an ideal implant material should perform as if it were equivalent
to the host tissue, the tissue at the interface should be equivalent to the
normal host tissue, and the response of the material to physical stimuli should
be like that of the tissue it replaces. (Hench, 2000)

The
purpose of this study is this study is to determine the optimal trace element
mixture to enhance hydroxyapatite bioceramic and design an optimal
computational model of the bioceramic, in order to further research on
bioceramic alternatives to prosthetics. Bioceramics are a better alternative to
prosthetics, because it bonds better to the bone. Finding the best trace
element additive that allows the bioceramic to bond best, would help the
medical sciences, and producing a computational model would allow for easier
accessibility for preliminary test of bioceramic efficiency.

Literature
Review

            Bioceramics are classified according
to their bioactivity, and the various classes of bioceramics include the
following: bioinert (such as alumina dental implant), bioactive
(hydroxyapatite), surface active (bioglass), and bioresorbable (tricalcium
phosphate implant). Bioceramics can potentially be used as body-interactive
materials, helping the body to heal, or promoting regeneration of tissues, thus
restoring physiological functions.

            Calcium
phosphate bioceramics has extensive usage in the medical field including as
substitutes for bone material, and tissue engineering scaffolding, for medical
cement and coatings, and for drug delivery systems due to a unique similarity
to the mineral portion of the bone tissue, relative ease of processing and good
cell attachment (Lobo & Arinzeh, 2010). Calcium phosphate ceramics has
significant properties including biocompatibility, safety in usage,
predictability of results, unlimited commercial procurement, and cost
effectiveness. These features represent significant advantages over autografts
and allografts and make them an excellent choice for medical applications such
as neurosurgery, reconstructive surgery, orthopedics, dentistry, maxilla and
craniofacial surgeries, and spinal surgery.

Calcium-phosphate
ceramics is inorganic materials that are conducive to the biological processes.
The fundamental property of bioactive ceramics is its ability to bond to bone
tissue material. Analysis of the bone implant interfaces have revealed that the
presence of hydroxyapatite is one of the key features in the bonding zone. A
variety of events occur at the bioactive ceramic tissue interface: dissolution
from the ceramic, precipitation from solution onto the ceramic, ion exchange
and structural rearrangement at the ceramic- tissue interface, interdiffusion
from the surface boundary layer into the ceramic, solution-mediated effects on
cellular activity, deposition of either the mineral phase or the organic phase
without integration into the ceramic surface, deposition with integration into the
ceramic, chemotaxis to the ceramic surface, cell attachment and proliferation,
cell differentiation, extracellular matrix formation (Ducheyne & Qiu,
1999).

The
examination of the behavior of bioactive materials demonstrates that positive
results occur because of the formation of a stable, and secure connection with
both bone and soft connective tissues. There is also newly discovered evidence
that certain compositions of bioactive glasses react at a cellular level in the
body to enhance bone proliferation; also termed “osteoproduction”.
“The greatest promise for achieving extensive improvements in the long-term
clinical repair of the skeletal system is to concentrate research and
experimentation about creating a new generation of biomaterials that enhance the
body’s repair mechanisms, i.e., regeneration of tissues.” (Hench, 2000)

Calcium
phosphate bioceramics can be considered one of the best materials for bone
substitution in comparison to other bone substitutes. Calcium phosphate
bioceramics are unique in that they have enhancing properties for bone
substitution compared with other bioceramics. Their compositional makeup is
remarkably similar to the minerals found in the bone material and thus can
produce a similar reaction as in human anatomy when bones are regenerated.
(Barrère, van Blitterswijk, & de Groot, 2006). Bone is made up of 70% of
hydroxyapatite, which is a mineral form of calcium apatite.  Calcium apatite found in bone mineral
contains non-apatitic carbonate and phosphate compounds. These groups are
extremely volatile, physically and structurally unstable and have a high
chemical reaction. However, they can be stabilized. Several calcium phosphate
growth inhibitors can help maintain the amorphous state. An example of such is
magnesium. Bone mineral apatite is derived from calcium phosphate clusters,
(Ca9 (PO4)6), packed with water in a random pattern to form amorphous calcium
phosphate. (Barrère et al., 2006). Furthermore, there is research that has
shown that the trace elements that exist in the extracellular fluids and bone
apatite may have a critical part in the level of health in our bones.

“Also,
the incorporation of mineral ions such as zinc or silicate in calcium phosphate
bioceramics showed an increase amount attachments of osteoblasts and had also
demonstrated a greater increase in proliferation” (Barrère et al., 2006).
Recently it has been found that incorporating the trace elements, zinc, and
silicate ions, in tri-calcium phosphate bioceramic (TCP) and hydroxyapatite
(HA) bioceramics were found to have a significant influence on osteogenesis,
the formation of bone. Calcium phosphates have inherent properties that
encourage bone regeneration.

Amorphous
calcium phosphate (ACP) is a type of inorganic amorphous calcium phosphate
material. This man-made material is produced when soluble salts of calcium and
phosphorous are mixed and combined. ACP is a known as a reactive and soluble
calcium phosphate compound. ACP rapidly releases calcium and phosphate ions
convert to apatite, and remineralize bone structure.

The
amorphous calcium phosphate can form exclusively during the solid-glass phase
that results from a physical chemical phenomenon. This phenomenon occurs when
adsorbed serum proteins halt the growth and nucleation reactions and prevents
transformation to a carbonated apatite substance. Additionally, the other
reactions in the glass are not prevented, as Ca and P diffusion creates a
thickening of the Ca-P rich-zone under the protein layer. The adsorption of the
protein layer is important since it provides for sites for the connection of
bone cells. These cells can be identified as the osteoblasts cells and their
progenitors. The regulation of osteoprogenitor cells for osteoblasts that forms
bone tissue in bioactive glass particles has been shown experimentally. The
high levels of fibronectin at the top layer of the bioactive glass transforms
to calcium-phosphate and improves the properties of the osteoblast cells.

A
biologically reactive hydroxycarbonate apatite (HCA) layer is equivalent to the
inorganic mineral phase found in human bone. The growing HCA layer provides an
ideal environment for the cellular reaction steps. These steps include
colonization by osteoblasts (the cells that make bone), followed by
proliferation and differentiation of the bone cells to form new bone that is
strongly bonded to the implant surface.

Repairing
bones with the shortest amount of recovery time involves the quick spreading
and differentiation of osteoblasts cells. A sequence of genes in the
osteoblasts must be activated where they undergo individual cell division and
creates a matrix of cells through which mineralization occurs to produce bone
tissue. “Seven families of genes are upregulated within 48 hours of the
exposure of primary human osteoblasts to the ionic dissolution products of
bioactive material. The activated genes creates numerous proteins that
influence all aspects of differentiation and proliferation of osteoblasts
including: “transcription factors and cell cycle regulators, signal
transduction molecules, DNA synthesis, repair, and recombination proteins,
growth factors and cytokines that influence the inflammatory response,
cell-surface antigens and receptors, extracellular-matrix components, and
apoptosis regulators” (Hench, 2000).

            Bioceramics are tested in several
ways, two of which will be discussed. In the four point bend
test method of testing, a rectangular sample of each calcium phosphate
bioceramic, containing a mixture of zinc and another trace element, is
subjected to a four point bending test. During the bending test, a bioceramic
sample is selected that ten cm long, ten mm wide, and ten mm tall. Then the
bioceramic sample is placed on the setup for the four point bend test. There
are two supports located five centimeters apart. Also, the actuator applies two
forces on the bioceramic sample. These two forces are placed three centimeters
apart. Additionally, on each side, the actuator pins will be located a distance
of one centimeter from the two supports.

When
testing, the Instron records the force (in Newtons), and the deformation (in
millimeters) of the bioceramic sample. The measurements of exerted force and
deformation are taken immediately before failure. After recording the values,
it can be assumed that the two forces acting on the specimen are the force
value divided by the deformation value. Then the maximum flexural strength (?)
and Young’s Modulus (E) of the bioceramic sample can be determined.

Producing
a computational model would allow for easier accessibility for preliminary test
of bioceramic efficiency, computer
simulation modeling will be used. Computer simulation has been making
breakthroughs in research. However, computer simulation in the field of biology
or chemistry is not as common as in engineering. But, using computer simulation
for modeling can enhance the design and evaluation of bioceramic structures. It
can be used to model a real or proposed system using computer software and is
useful when experimental changes to the system are costly or time-consuming,
providing easily accessible insight into the operation of systems that would be
otherwise impossible to analyze.

Modeling of systems is traditionally a mathematical
model, where analytical solutions to problems are found through predictions of behavior
of the system from a set of parameters and initial conditions. Computer
simulations build on purely mathematical models as a more comprehensive
method for studying systems. The approach to computer simulation involves designing
a model, incorporating the model in computer program, determining the premises of
variables, and evaluating the data. This allows for effective evaluation of the
entire system to make inferences about the system that is being model.
“Successful simulation studies do more than compute numbers. They make use of a
variety of techniques to draw inferences from these numbers. Simulations make
creative use of calculation techniques that. As such, unlike simple
computations that can be carried out on a computer, the results of simulations
are not automatically reliable. Much effort and expertise goes into deciding
which simulation results are reliable and which are not” (Winsberg, 2010).

Two types of computer simulation will be used in this study: equation-based simulations and
agent-based simulations. Equation-based simulations
are based on an established theory to guide the design of a mathematical model
based on differential equations. Equation-based simulations can either be particle
based — using individual variables and a set of differential equations — or field-based
— using a set of time related equations in a continuous medium or field.

Agent-based simulations are used
in fields studying the interaction of many individuals. Agent-based simulations
can resemble equation-based
simulation, more specifically particle-based simulations, where they
represent the behavior of several distinct individuals. But unlike equation-based
simulations, agent-based simulations do not have pre-existing differential
equations to direct the modeling of the individuals.

The
specific computer simulation program that will be used is Finite Element Analysis
(FEA). This method uses the finite element method to analyze a model of the bioceramic
and uses data to predict how applied stressors will affect the biomaterial or bioceramic
design. FEA is useful in determining areas of weakness in a design for future
improvements. Finite element analysis is done through creating a mesh of points
in the shape of the object that is being modeled. Each mesh has data about the bioceramic
material that is point-analyzed. FEA analyzes the reaction to high-stress on an
object, which is necessary to ensure the bioceramic material is strong enough
to be applied in the prosthetics field.

Finite element analysis is extremely useful in predicting
the possible reactions the bioceramic would have in application. FEA helps improve
the quality and function of the bioceramic, by computing the individual
component behavior and analyzing it to predict the overall behavior.

There are several steps involved in running a Finite
Element Analysis. The geometry of the model has to be first defined. Next
properties are assigned to all elements that consist within the model. Loading
of the analysis is then performed. A mesh would then be generated by the FEA
software and the analysis is run and results are obtained both graphically and
numerically. Additionally, there are several types of FEA analysis. These
include linear
static stress analysis, frequency & buckling analysis, dynamic analysis,
non-linear analysis, analysis of composites, thermal analysis, fatigue
analysis, CFD fluid flow analysis, and design optimization.

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