An Bone is a mineralized tissue made out

Anessential component of the skeletal system is bone structure. The main featuresof bone structure include providing body support, motion, and production. Thebody’s bone structure serves many important functions of the human body. Itprotects the body and is a location for the creation of specialized tissuessuch as bone marrow, the body’s system that creates blood. Also, bone structureplays a huge role in structurally supporting the mechanical action of thebody’s soft tissues.

For example, the contraction of muscles to move orexpansion of lungs to breathe. Having a healthy bone structure has asignificant relevance to the body, as it also serves as a mineral reservoir,where endocrine systems regulate the level of phosphate and calcium ions in thebody 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 amineralized tissue made out of an organic matrix that is strengthened byaccumulation of calcium phosphate compounds. In summary, this means that boneis a natural composite material. The compositional make-up of the organicmatrix in bone consists of three main components.

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These three main componentsinclude the following: approximately 95% collagen type I fibers, proteoglycans,and many different types of non-collagenous proteins. The organic matrix inbone is calcified by calcium phosphates minerals and works to embed bone cells.These bone cells are called the osteoprogenitor cells and participate in themaintenance of the bone structure and the organization of bone. They includethree types: osteoblasts, osteocytes, and osteoclasts.

Abiomaterial is any non-pharmaceutical material that can be used to treat orreplace any tissue, organ, or function in an organism. Biomaterial research isone of the most important fields of modern medicine used in organ transplant, woundhealings, drug delivery, and prosthetic replacements. The main focus of thisstudy is to investigate biomaterial, more specifically bioceramic, onprosthetic enhancement or replacement. Certain characteristics of biomaterialsmake them the preferred choice for medical applications, and these include thefollowing: they are biodegradable, biocompatible, and non-toxic.

The differentclasses of biomaterial include polymers, metals, ceramics (including carbons,glass-ceramics, and glasses), and natural materials (both from plants andanimals) (Ige, Aribo, & Umoru, 2012).Whena bioactive material is incorporated into the body’s structure, severalbiological reactions occur at the implant-tissues interface that result in amechanically stable chemical interfacial bonding called bioactive fixation.Also, several key requirements need to be fulfilled for successful use ofbiomaterials, an ideal implant material should perform as if it were equivalentto the host tissue, the tissue at the interface should be equivalent to thenormal host tissue, and the response of the material to physical stimuli shouldbe like that of the tissue it replaces. (Hench, 2000)Thepurpose of this study is this study is to determine the optimal trace elementmixture to enhance hydroxyapatite bioceramic and design an optimalcomputational model of the bioceramic, in order to further research onbioceramic alternatives to prosthetics.

Bioceramics are a better alternative toprosthetics, because it bonds better to the bone. Finding the best traceelement additive that allows the bioceramic to bond best, would help themedical sciences, and producing a computational model would allow for easieraccessibility for preliminary test of bioceramic efficiency.LiteratureReview            Bioceramics are classified accordingto their bioactivity, and the various classes of bioceramics include thefollowing: bioinert (such as alumina dental implant), bioactive(hydroxyapatite), surface active (bioglass), and bioresorbable (tricalciumphosphate implant).

Bioceramics can potentially be used as body-interactivematerials, helping the body to heal, or promoting regeneration of tissues, thusrestoring physiological functions.             Calciumphosphate bioceramics has extensive usage in the medical field including assubstitutes for bone material, and tissue engineering scaffolding, for medicalcement and coatings, and for drug delivery systems due to a unique similarityto the mineral portion of the bone tissue, relative ease of processing and goodcell attachment (Lobo & Arinzeh, 2010). Calcium phosphate ceramics hassignificant properties including biocompatibility, safety in usage,predictability of results, unlimited commercial procurement, and costeffectiveness. These features represent significant advantages over autograftsand allografts and make them an excellent choice for medical applications suchas neurosurgery, reconstructive surgery, orthopedics, dentistry, maxilla andcraniofacial surgeries, and spinal surgery. Calcium-phosphateceramics is inorganic materials that are conducive to the biological processes.

The fundamental property of bioactive ceramics is its ability to bond to bonetissue material. Analysis of the bone implant interfaces have revealed that thepresence of hydroxyapatite is one of the key features in the bonding zone. Avariety of events occur at the bioactive ceramic tissue interface: dissolutionfrom the ceramic, precipitation from solution onto the ceramic, ion exchangeand structural rearrangement at the ceramic- tissue interface, interdiffusionfrom the surface boundary layer into the ceramic, solution-mediated effects oncellular activity, deposition of either the mineral phase or the organic phasewithout integration into the ceramic surface, deposition with integration into theceramic, chemotaxis to the ceramic surface, cell attachment and proliferation,cell differentiation, extracellular matrix formation (Ducheyne & Qiu,1999).Theexamination of the behavior of bioactive materials demonstrates that positiveresults occur because of the formation of a stable, and secure connection withboth bone and soft connective tissues. There is also newly discovered evidencethat certain compositions of bioactive glasses react at a cellular level in thebody to enhance bone proliferation; also termed “osteoproduction”.

“The greatest promise for achieving extensive improvements in the long-termclinical repair of the skeletal system is to concentrate research andexperimentation about creating a new generation of biomaterials that enhance thebody’s repair mechanisms, i.e., regeneration of tissues.” (Hench, 2000)Calciumphosphate bioceramics can be considered one of the best materials for bonesubstitution in comparison to other bone substitutes. Calcium phosphatebioceramics are unique in that they have enhancing properties for bonesubstitution compared with other bioceramics.

Their compositional makeup isremarkably similar to the minerals found in the bone material and thus canproduce a similar reaction as in human anatomy when bones are regenerated.(Barrère, van Blitterswijk, & de Groot, 2006). Bone is made up of 70% ofhydroxyapatite, which is a mineral form of calcium apatite.  Calcium apatite found in bone mineralcontains non-apatitic carbonate and phosphate compounds. These groups areextremely volatile, physically and structurally unstable and have a highchemical reaction. However, they can be stabilized.

Several calcium phosphategrowth inhibitors can help maintain the amorphous state. An example of such ismagnesium. Bone mineral apatite is derived from calcium phosphate clusters,(Ca9 (PO4)6), packed with water in a random pattern to form amorphous calciumphosphate. (Barrère et al., 2006).

Furthermore, there is research that hasshown that the trace elements that exist in the extracellular fluids and boneapatite 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 phosphatebioceramics showed an increase amount attachments of osteoblasts and had alsodemonstrated a greater increase in proliferation” (Barrère et al., 2006).Recently it has been found that incorporating the trace elements, zinc, andsilicate 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 thatencourage bone regeneration.Amorphouscalcium phosphate (ACP) is a type of inorganic amorphous calcium phosphatematerial. This man-made material is produced when soluble salts of calcium andphosphorous are mixed and combined.

ACP is a known as a reactive and solublecalcium phosphate compound. ACP rapidly releases calcium and phosphate ionsconvert to apatite, and remineralize bone structure.Theamorphous calcium phosphate can form exclusively during the solid-glass phasethat results from a physical chemical phenomenon.

This phenomenon occurs whenadsorbed serum proteins halt the growth and nucleation reactions and preventstransformation to a carbonated apatite substance. Additionally, the otherreactions in the glass are not prevented, as Ca and P diffusion creates athickening of the Ca-P rich-zone under the protein layer. The adsorption of theprotein layer is important since it provides for sites for the connection ofbone cells.

These cells can be identified as the osteoblasts cells and theirprogenitors. The regulation of osteoprogenitor cells for osteoblasts that formsbone tissue in bioactive glass particles has been shown experimentally. Thehigh levels of fibronectin at the top layer of the bioactive glass transformsto calcium-phosphate and improves the properties of the osteoblast cells.Abiologically reactive hydroxycarbonate apatite (HCA) layer is equivalent to theinorganic mineral phase found in human bone. The growing HCA layer provides anideal environment for the cellular reaction steps.

These steps includecolonization by osteoblasts (the cells that make bone), followed byproliferation and differentiation of the bone cells to form new bone that isstrongly bonded to the implant surface.Repairingbones with the shortest amount of recovery time involves the quick spreadingand differentiation of osteoblasts cells. A sequence of genes in theosteoblasts must be activated where they undergo individual cell division andcreates a matrix of cells through which mineralization occurs to produce bonetissue. “Seven families of genes are upregulated within 48 hours of theexposure of primary human osteoblasts to the ionic dissolution products ofbioactive material. The activated genes creates numerous proteins thatinfluence all aspects of differentiation and proliferation of osteoblastsincluding: “transcription factors and cell cycle regulators, signaltransduction molecules, DNA synthesis, repair, and recombination proteins,growth factors and cytokines that influence the inflammatory response,cell-surface antigens and receptors, extracellular-matrix components, andapoptosis regulators” (Hench, 2000).            Bioceramics are tested in severalways, two of which will be discussed.

In the four point bendtest method of testing, a rectangular sample of each calcium phosphatebioceramic, containing a mixture of zinc and another trace element, issubjected to a four point bending test. During the bending test, a bioceramicsample is selected that ten cm long, ten mm wide, and ten mm tall. Then thebioceramic sample is placed on the setup for the four point bend test.

Thereare two supports located five centimeters apart. Also, the actuator applies twoforces on the bioceramic sample. These two forces are placed three centimetersapart.

Additionally, on each side, the actuator pins will be located a distanceof one centimeter from the two supports. Whentesting, the Instron records the force (in Newtons), and the deformation (inmillimeters) of the bioceramic sample. The measurements of exerted force anddeformation are taken immediately before failure. After recording the values,it can be assumed that the two forces acting on the specimen are the forcevalue divided by the deformation value. Then the maximum flexural strength (?)and Young’s Modulus (E) of the bioceramic sample can be determined. Producinga computational model would allow for easier accessibility for preliminary testof bioceramic efficiency, computersimulation modeling will be used.

Computer simulation has been makingbreakthroughs in research. However, computer simulation in the field of biologyor chemistry is not as common as in engineering. But, using computer simulationfor modeling can enhance the design and evaluation of bioceramic structures.

Itcan be used to model a real or proposed system using computer software and isuseful when experimental changes to the system are costly or time-consuming,providing easily accessible insight into the operation of systems that would beotherwise impossible to analyze.Modeling of systems is traditionally a mathematicalmodel, where analytical solutions to problems are found through predictions of behaviorof the system from a set of parameters and initial conditions. Computersimulations build on purely mathematical models as a more comprehensivemethod for studying systems. The approach to computer simulation involves designinga model, incorporating the model in computer program, determining the premises ofvariables, and evaluating the data. This allows for effective evaluation of theentire system to make inferences about the system that is being model.”Successful simulation studies do more than compute numbers.

They make use of avariety of techniques to draw inferences from these numbers. Simulations makecreative use of calculation techniques that. As such, unlike simplecomputations that can be carried out on a computer, the results of simulationsare not automatically reliable. Much effort and expertise goes into decidingwhich simulation results are reliable and which are not” (Winsberg, 2010).

Two types of computer simulation will be used in this study: equation-based simulations andagent-based simulations. Equation-based simulationsare based on an established theory to guide the design of a mathematical modelbased on differential equations. Equation-based simulations can either be particlebased — 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 usedin fields studying the interaction of many individuals. Agent-based simulationscan resemble equation-basedsimulation, more specifically particle-based simulations, where theyrepresent the behavior of several distinct individuals. But unlike equation-basedsimulations, agent-based simulations do not have pre-existing differentialequations to direct the modeling of the individuals. Thespecific 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 bioceramicand uses data to predict how applied stressors will affect the biomaterial or bioceramicdesign.

FEA is useful in determining areas of weakness in a design for futureimprovements. Finite element analysis is done through creating a mesh of pointsin the shape of the object that is being modeled. Each mesh has data about the bioceramicmaterial that is point-analyzed. FEA analyzes the reaction to high-stress on anobject, which is necessary to ensure the bioceramic material is strong enoughto be applied in the prosthetics field.Finite element analysis is extremely useful in predictingthe possible reactions the bioceramic would have in application. FEA helps improvethe quality and function of the bioceramic, by computing the individualcomponent behavior and analyzing it to predict the overall behavior.

There are several steps involved in running a FiniteElement Analysis. The geometry of the model has to be first defined. Nextproperties are assigned to all elements that consist within the model. Loadingof the analysis is then performed. A mesh would then be generated by the FEAsoftware and the analysis is run and results are obtained both graphically andnumerically. Additionally, there are several types of FEA analysis.

Theseinclude linearstatic stress analysis, frequency & buckling analysis, dynamic analysis,non-linear analysis, analysis of composites, thermal analysis, fatigueanalysis, CFD fluid flow analysis, and design optimization.


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