Dental Hypotheses

ORIGINAL RESEARCH
Year
: 2020  |  Volume : 11  |  Issue : 3  |  Page : 74--85

Fabrication and Characterization of Porous Bioceramic-Magnetite Biocomposite for Maxillofacial Fractures Application


Amirsalar Khandan1, Ehsan Nassireslami2, Saeed Saber-Samandari3, Nahid Arabi4,  
1 Toxicology Research Center, AJA University of Medical Sciences, Tehran, Iran
2 Toxicology Research Center, AJA University of Medical Sciences, Tehran; Department of Pharmacology and Toxicology, AJA University of Medical Sciences, Tehran, Iran
3 New Technologies Research Center, Amirkabir University of Technology, Tehran, Iran
4 Pediatric Oncology & Hematology, Pediatric Department, AJA University of Medical Sciences, Tehran, Iran

Correspondence Address:
Ehsan Nassireslami
Department of Pharmacology and Toxicology, AJA University of Medical Sciences, Tehran
Iran

Abstract

Introduction: Advantages of using porous bio-nanocomposite scaffolds for maxillofacial fracture application and optimizing the internal surfaces of synthetic grafts using nanotechnology can accelerate the bone cell adhesion, mechanical properties and absorption rates. There are various studies that have been performed on porous scaffold, especially for the fractured and destroyed parts of the facial bones. The aim of this study was to investigate the experimental and numerical analysis of the porous scaffold, which undertakes static and dynamic loading conditions. Materials and Methods: The maxillofacial bone was modeled using the solid works software, and then it was inserted into the Abaqus software to achieve a more precise model that utilizes an isotropic linear substance. Thereafter, a proper micromechanical model reported evaluating the elastic modulus response on porosity value using various models. Additionally, an experimental analysis was conducted on a new calcium silicate (CS) bioceramic reinforced with magnetite nanoparticles (MNPs) using the space holder technique coated with the gentamicin drug loaded on gelatin polymer. The response of the bio-nanocomposites shape, which corresponds to different MNPs’ weight fractions, was determined using the scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. Results: The analysis of the scaffold implant showed that it is tightened at a torque of stiffness of 3 mm in the implant, which leads to high mechanical tension. The results showed that the elastic modulus of the nanocomposites increased from 60±5 MPa to 145±5 MPa with increasing 15 wt% MNPs to the calcium silicate nanoparticles. Conclusion: The results indicated that addition of 15 wt% MNPs to the based bioceramics increased both compression strength and decrease the porosity value.



How to cite this article:
Khandan A, Nassireslami E, Saber-Samandari S, Arabi N. Fabrication and Characterization of Porous Bioceramic-Magnetite Biocomposite for Maxillofacial Fractures Application.Dent Hypotheses 2020;11:74-85


How to cite this URL:
Khandan A, Nassireslami E, Saber-Samandari S, Arabi N. Fabrication and Characterization of Porous Bioceramic-Magnetite Biocomposite for Maxillofacial Fractures Application. Dent Hypotheses [serial online] 2020 [cited 2020 Sep 28 ];11:74-85
Available from: http://www.dentalhypotheses.com/text.asp?2020/11/3/78/290458


Full Text



 Introduction



The maxillofacial bone is an important tissue in human bone that requires nutrients, oxygen, heat, and pressure to be alive and have interaction with its surrounding parts.[1],[2] Bones have the preposterous capability to repair themselves and act as a structural architecture that holds all the parts of the body outright.[3] Generally, a bone is a solid body that forms the skeleton of the humans and animals in miscellaneous parts of the body with an organic substance like collagen, and mineral substances like calcium phosphate (CaPs) and calcium carbonate (CaC).[4],[5],[6],[7] The weak mechanical properties of the bone lead to some specific diseases and problems like osteoporosis and sudden fracture depending on human lifestyle. Collagen and adipose tissue play important rule as the mechanical support for our vital organs, which is responsible for the storage of mineral elements like CaF2, Ca2+ and PO42-.[8],[9],[10],[11],[12],[13] The upper part of the long bones has a crystalline permeable nanostructure called trabecular, which directly binds to the blood vessels of the bone marrow as well as adjusting its calcium level by providing calcium ions.[14],[15],[16] Khandan et al.[16] stated that flour hydroxyapatite (FHA) produced using mechanochemical procedure reinforced with titanium oxide (TiO2) has suitable mechanical and chemical stability regarding the composition of FHA and TiO2 powder. The study showed that when FHA is placed in an aqueous medium, the longer the storage time, the lower the crack growth’s resistance with higher apatite formation on the surface of the porous scaffold.[17] Therefore, the second phase (TiO2) of the composites is incorporated for clinical applications and advantageous. This includes biodegradable agent like TiO2, ZrO2, the coating on metal implants, and granular filler for direct application into the human facial tissues.[18],[19] Moreover, special types of reinforcements particle or cancer therapy treatments like hyperthermia can be likewise carried out.[20],[21],[22],[23],[24],[25] Although the studies in tissue engineering area are rapidly developing, there is still a gap between the commercial advances and the clinical applications of the engineered products. Therefore, in this study we aimed to conduct an experimental analysis on new calcium silicate, reinforced with MNPs as an ideal scaffold with the non-toxic, biocompatible and biodegradable property. This is mimicking the bone part using Abaqus software to enhance the cell and gene activation. Additionally, the coordination of the mechanical properties of the hard tissue with the host tissue is important; thus, the hybrid materials have expanded to optimize the mechanical properties of the scaffolds.

 Materials and Methods



Bioceramic powder preparation

In order to prepare the calcium silicate (CS) powder, homogenize-based bioceramic was used after being synthesized with a high-energy ball milling process (HEBM) similar to previous works.[19],[25] The specific amount of calcium silicate was milled using the HEBM for two hours with the zirconia vial and balls. The ball to powder weight ratio was taken as 15:1, the rotational speed at 650 rpm, and N2 gas at room temperature (T) of 37°C.

Preparation of CS-MNPs nanocomposite

In the next step, the produced CS powder mentioned in subsection 2.1 was composed of pure magnetite nanoparticle (MNPs: Fe3O4) at different weight fractions of (0, 5, 10, and 15-wt%), with an average crystallite size of 50–100 nm. The MNPs were synthesized by co-precipitation technique as explained in detail in the literature.[19],[25] Afterward, the two nanopowders were milled using HEBM process for 60 min to obtain a homogenize nanocomposite. Then the nanocomposite powder was kept in the oven to avoid agglomeration.

Scaffold preparation via space holder technique

Using a universal testing machine for 50–65 s, the obtained powder was compressed by an applied pressure of 150–200 MPa in a cylindrical die with a force-extension curve similar to that of the powder metallurgical (PM) technology. It should be noted that the applied pressure on the sample powders led to different force-extension curves under the same condition. The nanocomposite powders were added to 65–70 wt% sodium chloride (NaCl) particles with micron size with 98% purity (Merck Company, Germany). Subsequently, in order to prepare CS-MNPs porous cylindrical scaffolds via the space holder method with NaCl particles were inserted into a steel die for 50 seconds. In stage one, the obtained mixture of the powders was added with sunflower oil in the die. After that, the temperature of the obtained bio-nanocomposite scaffolds was reduced to the local temperature at the rate of 10°C/min. The samples were sintered in the N2 gas atmosphere to compact it at 1100°C for 110 minutes. The micron size NaCl particles were eliminated from the scaffold tissue after being in the furnace. The remained NaCl particles were eliminated by immersing the samples in distilled water for 1 day at the room temperature. Furthermore, the porous samples were removed from the deionized solution and were kept in the oven at 100°C to eliminate any other additional moisture and then kept in the oven. Then, the samples were immersed in the chitosan solution loaded with gentamicin drug. After that, the scaffolds were removed and were kept at the room temperature. The prepared samples then were soaked in the gelatin-gentamicin drug to coat the porous scaffold. Specific amount of gelatin was poured into the distilled water loaded with 2 mg gentamicin drug stirrer for 4 h at 50°C and 500 rpm.

Material characterization

The morphology of the magnetic nanoparticle on the scaffold was evaluated using scanning electron microscopy (SEM) to extract required supporting information in order to characterize the materials’ morphology and microstructural influence on the properties of the CS-magnetite scaffold and nanocomposite with space holder technique. For SEM images, the prepared scaffold nanocomposite was coated with a sprayed gold using a high vacuum for 3 minutes with a Vega II machine (OZ Machine, Istanbul, Turkey) under 30–40 kV were used at central laboratory of Amirkabir University of Technology, Tehran, Iran. The elastic modulus of the porous scaffold was determined from the stress-strain curve (S-S, first linear curve slope). A porous cylindrical scaffold having a dimension of 6×10 mm (diameter × height) was created using a computer-controlled universal machine by selecting 2 mm/min as a rate of the ramp for mechanical testing evaluation. To evaluate the phases of nanopowders, X-ray diffraction (XRD) and Equinox 300 were used at a range of 2θ between 10° to 90° under 40 kV and 30 mA using Philips machine and X pert software at Tehran Polytechnic, central research lab (Tehran Polytechnic, composite research lab).

Testing Materials

Compressive strength evaluation

The mechanical performance (compressive strength) of the novel scaffold made of CS-MNPs with a height of 10 mm and diameter of 6 mm according to the ASTM-D5024-95a standard using a compression universal testing machine was performed with a crosshead speed of 2-4 mm/min under 10 kN force. The elastic modulus of the specimen after the test was recorded with respect to the Hooke’s equation with standard deviation (SD = ±3). The outcome of the mechanical test used for determination of elastic modulus which is the slope of the linear part of the stress-strain curve. In order to obtain the compressive strength value, equation (1) was applied:

[INLINE:1]

Also, the Poisson’s ratio was evaluated using equation II as a ratio of the total transverse elastic deformation to its axial elastic deformation:

[INLINE:2]

Where εy is the transverse strain obtaining from the applied axial strain εx in a 2D Cartesian coordinate system with an orthogonal x- and y-axes. [Table 1] shows the mechanical properties of the porous bio-nanocomposite with 0, 5, 10 and 15-wt % MNPs in bioceramic base materials. The nanocomposite elastic modulus, density and the Poisson ratio of the samples were recorded. The comparison between the initial mechanical properties such as elastic modulus, density, and the Poisson ratio of the real bone and synthetic bone is shown in [Table 2] for cortical, trabecular and cancellous bone.{Table 1}{Table 2}

Porous magnetic bio-nanocomposite porosity evaluation

In this study, the porosity of the produced CS-MNPs bio-nanocomposite scaffolds was assessed using the Archimedes formula in Simulated Body Fluid (SBF) and Phosphate Buffer Saline (PBS) produced according to the Kokubo[26] procedure which is stated below as equation (3):

[INLINE:3]

Afterwards, the Archimedes method is used to measure the porosity of the bio-nanocomposite scaffold using equation (4).

[INLINE:4]

The porous scaffold samples were tested for the porosity evaluation of the samples and rechecked multiple times, that is at least three consecutive times in order to have a high accuracy on the test.

Model using finite element analysis (FEA)

To investigate the biomechanics of each part of the scaffold, a 3D model of that part was created using the solid work and Abaqus modeling software. After making the model, a biomechanical investigation was carried out using the FEA. At first, it was organized as some components or smaller elements. These components or elements were connected to a limited number of points which are called nodes. After obtaining a numerical solution of the governing equations for each of the nodes around the element, the behavior of that element became personal. Bringing together the results of all the elements, the behavior of each particular physical system can be achieved. The obtained results from the experimental analysis were used to predict the effect of compressive strength and the porosity was simulated using Abaqus software version 16 software assault Systems SIMULIA’s Abaqus/Standard FEA Solver. The cylindrical shape was drawn in the CATIA and then the exact models with similar geometry of the human bone were simulated with computer tomography (CT) scan images. The complexity of the geometry leads to incompatibility with the mathematical descriptions of the common geometries used in engineering and 3D design. Thus, in this study, the computer modeling of the scaffold bone geometry including a large number of fabricated tiny cubic pieces were simulated.

Optimization

The experimental results were optimized using least square methods (MATLAB, or Simulink® software, Version 2.1 of the Optimization Toolbox). It was used to find the maximum and minimum values in a wide range of data.

 Results



XRD results

[Figure 1] (a-b) illustrates the XRD pattern of CS bioceramic and magnetite nanoparticles used in the current study. The phase characterization showed that the CS has crystalline size structure with a sharp peak. The MNPs have five major important peaks which show high purity of MNPs with size less than 100 nm.{Figure 1}

SEM results

[Figure 2] (a–c) shows the SEM micrograph of CS powder, MNPs, CS-MNPs scaffold using space holder technique with an effect of NaCl microparticles. The SEM images show the white particles with an agglomerated particle with size 100-200 nm. [Figure 2] (b) indicates the morphology of the MNPs with a dark color. As shown in [Figure 2] (a–c), the SEM micrograph of the samples with the space-holder technique can produce pore size as the spacer size changes from 2 to 3 micron size. It is believed that the scaffold microstructure significantly contributes to the development of specific biological functions in the hard tissues and provides the proper nutrition and spatial organization for cell growth and cell immigration. The reproduction of special tissues using synthetic materials depends on the porosity and size of the pores of the three-dimensional protective nanostructure. The large surface area facilitates cell attachment and growth, given that the large porosity volume is required for adaptation and thus provides sufficient cell mass to improve tissue properties.{Figure 2}

Porosity results

[Figure 3] represents the porous size with 0.5, 0.6, and 0.7 microns with square, round, and oblique diagonal cylindrical shape. The obtained results from the FEA and experimental analysis showed that the FEA measured sufficient elastic modulus was increased with respect to the changing diameter of the cylindrical scaffold, i.e. from 0.6 microns to 0.7 microns the compressive strength increased more than two times. The CS powder evaluation had a range of 40 MPa, which were common between porous and compact bones. The compression test results validated the similarity between the finite element model (FEM) and experimental analyses. The final results showed that the different geometries like the pore size and the porosity of the scaffold caused some error (less than 10%). The deformations continued via overlapping of the physical microstructures until the porous specimen was ultimately fractured. The most important part of the design porous scaffold is to determine the size of the cavities, the intensity of the porosity, and the degree of degradation, so that by the time of degradation it has been able to withstand the stresses of the area and apply these pressures throughout the area.{Figure 3}

[Figure 4] showed the assembly and interaction of the maxillofacial architecture of the drilled part with and without porous cylindrical scaffold. It is well recognized that several pores on the wall and curved surfaces undergo slight pattern differences from circle shape to elliptical shape because of the uniaxial compressive deformation. The elastic modulus and uniaxial compression strength of the homogeneous scaffold were found to be 60 MPa and 145 MPa, respectively. On the other hand, when gridding and meshing for a FEM, the four elements that were utilized can be used with respect to the number of elements, which are used later in the meshing process. The results illustrated that as the porosity increased, the slope of the elastic region decreased regarding its low toughness. On the other hand, the load-bearing capability of the scaffold with respect to the forces was reduced.{Figure 4}

 Discussion



In this research, the CS powder was synthesized using HEBM and magnetite nanoparticle precipitation technique. Afterward, the nanocomposite powder was compressed using a NaCl particle by employing the space holder technique, sintered at 1100°C for 110 min. [Figure 4] shows a higher strain and stress in the cylindrical shape affected by a specific amount of force which has an effect on the shape of the object to be changed even when the force is eliminated. The simulation shows that the fabricated scaffold nanocomposite does not return to its original state because of the low elasticity of the bioceramic. The observations show that the deformation is in the plastic region and remain permanent. [Figure 4] shows that a force over the area seems to accumulate at the tip of the horizontal axes of the elliptical pores and on the curved surfaces of the scaffolds. The results findings from the Abaqus model indicated that alteration in porous cylindrical shape were created by the force and vertical pressure leading to sudden or stress fracture of maxillofacial part. Due to the porosity of boney scaffolds, methods used to model porous materials were used to achieve their mechanical properties. In recent years, many researches have been proposed to obtain the elastic properties of porous materials, either experimentally or analytically in various biological environment.[27],[28],[29],[30],[31] The presented analytical methods can be divided into two categories generally.[32] The first category is based on the composite materials theory. In this group of models, the segment is considered to be a special case of a two-phase composite material. The second category of these models is cellular solids. These models are based on solid-state minimum methods, in which the material is considered as a single phase. Researchers have been able to produce bones known as hyperelastic with special materials and 3D printing technology. It is indicating that these bones can renovate the future of surgical surgeries. Surgeons can put these biomaterials under the skin to form tissue on them or use them directly as the bone in the patient’s facial fracture. Hyperelastic bones can be easily cut, bent, or attached together and may be used in different places without using adhesive materials. Scientists have tested hyper-elastic bones in different situations. One of the most important experiments ever undertaken has been the use of stem cells on these bones.[26],[27],[28],[29],[30],[31],[32],[33],[34] In another experiment, scientists placed hyperaesthesia bones under the skin of the mouse and found that the surrounding cells were integrated with the new member, and the body’s immune system reacted positively.[34] Furthermore, the dental surgeons used this hyper-elastic biomaterial as the main bone in the spine of a rat and as a part of the skull of an animal.[35],[36],[37],[38],[39],[40],[41],[42],[43] In these cases, the hyperelastic bone aligned well with the host body and made it possible to create blood tissues in the area. Elastic modulus, Poisson’s ratio and porosity in laboratory tests for nanocrystalline and MNPs were extracted and presented in [Table 1]. It was seen in Mancini et al.[44] study that porosity increases with increasing hydroxyapatite amount as an additive. In addition, it was observed that by increasing the additives, the crystallinity of product increased. Hence, based on the sample with the higher porosity, elastic modulus and the Poisson’s ratio of the Dewey’s model were evaluated.[43],[44],[45] The following changes encouraged us to search for the Elastic Modulus and CS as the purpose of the various pores size. In our current research, the obtained results indicated that the open porosity value matched properly with the cortical bone, but it is lower for the trabecular bones. The following results illustrate that the specimens had the least pore ranging from 50 to 10-micron size. This shows larger cells attachment for the primary days in other research works, although the proliferation of the cells in the pore range is quite slow in comparison with the larger pore’s sizes. The ultimate results indicate that the microstructure of the scaffolds plays an important role in cell attachment and bone growth in the animal. Carried out tests on the size of the pores helped monitoring the CS-MNPs scaffold nanocomposites. The ideal porosity of the scaffolds was measured and then, compared to the porosity of the samples that were modeled using the CAD software. The analysis showed that the ideal porosity, as well as the porosity that was measured through the CAD software, increased, however, this increase was lower than 10%. As the diameter of the scaffold increased from 0.6 microns, the strut witnessed its highest limit of fabrication size. Pore size was 0.6 micron, and the medium proper E of the scaffold along the axial and body directions was 15–30 MPa. The followed value had a porosity of 80% and was similar to the human cortical bone. With all these interpretations, the number of successful surgical procedures among the animals is low and in order to find a better result, more examples need to be tested. However, one of the important features of the artificial bone is its low production cost, which makes it a perfect candidate for widespread application in the future of clinical surgeries in which the 3D printing technology can reduce these costs. Ease of packaging, shipping, maintenance, and production capabilities based on patient requirements are its other benefits. Therefore, it can be produced for the required bone as each patient requires or on the other hand, individualized medicine comes true in this field. These features are especially ideal for developing countries with low health infrastructure. In this section, some of the most important models for calculating the effective elastic properties of porous architecture are presented. It should be noted that in the below correlations, E, ν, κ, ϕ, µ and ρ represent elastic modulus, the Poisson’s ratio, the volume modulus, the shear modulus, the porosity percentage, and the density, respectively. In addition, the sub clauses s and p also indicate porous and non-porous material. In this work, the defects of the sample which influenced the porosity were not modeled, hence the model utilized assumed an ideal model. [Figure 5] (a) shows that the Poisson ratio changes versus porosity changes have similar trend for DS and RGM model while the WTM model has the highest error. This might be due to low Poisson ratio value of approximately 0.2. [Figure 5] (b) evaluated the effect of porosity value on the elastic modulus of porous bio-nanocomposites. According to [Figure 5] (b), the RM model has the highest error while the DS and GM models have a similar trend to the experimental values. The RGM model does not simulate the proper model for elastic modulus and porosity value in these cases. As it was seen, in [Figure 5] (c) the ratio of E/ES corresponding to various porosity percentages of GM, RAM and RGM model shows a valid simulation close to the experimental data. [Figure 6](a-c) represents the optimum value of the porosity in various Poisson ratio for a sample containing various amount of MNPs. The trend shows that as the Poisson ratio of the sample increases, the decrease in reinforcement percentages of the porosity value has the medium range. [Figure 6] (b) shows that with an increase of the porosity value, the elastic modulus of the specimen decreased; however, the Poisson ratio has the lowest value. The obtained results indicated that the elastic and non-static features of cortical and trabecular bone architecture are derived from bone mass density (BMD), which can be estimated from the Hounsfield units, also it can be used from multiscale modelling of maxillofacial part.[25],[26],[27],[28],[29],[30],[31] [Figure 7] shows the simulation of maxillofacial part with Abaqus software with the porous scaffold architecture under various load, the red area shows the maximum stress that the part can tolerate for maxillofacial approaches. After complete modeling in CATIA software, the maxilla part was entered into the Abaqus analysis software. At this stage, the mechanical properties of the material should be determined with respect to the required analysis, the mode of analysis, the interconnection conditions between the components, the loading and boundary conditions, and finally the segment bonding. [Figure 7] (a-e) shows that as the jawbone destroyed, in gingivitis, the bacteria begin to eat the bone, and on the other hand, losing the tooth and not replacing it also causes the jawbone to disappear, knowing that the pressure that comes from chewing side. As later stated, the porous bony scaffold attaches completely to the bone after the jawbone is pulled during the weaving of the hard tissue. In this model it is assumed that the porous magnetite scaffold is fully attached to the bone and the osteogenesis is fully integrated. [Figure 7] shows the ultimate stress is diminished in the region or vicinity of the porous scaffold grooves, i.e. in the orientation of the load and in the nonexistence of load-bearing material’s volume components. The homogeneous scaffold structure is diffused or attached with bigger pores; therefore, the consequence of the separation of the stress profile due to the residence of these pores is much more. The strains were determined to be higher adjacent to the pores in the vertical axis to the loading region, as the load was fixed to alter its direction adjacent to the pores and consequently, focus on their regular apexes. The porous structure on the outer side of the sample approached each other and the encircling volume elements acted as a support and were subjected to a larger stress during the loading. The porosity value of the ceramic in facial application is raised over time as the bone grows with high pores and channels structure. For instance, the flexural strength of a porous implant (50–65%) reported about 40–60 MPa.[46],[47] Regarding the above-mentioned facts, the nanoceramics have high surface-to-volume ratios that allow for high drug loading and long-term release in the bone substitute. Advances in nanotechnology have resulted producing the ultra-small particles with high purity with a very high surface-to-volume ratio. This allows the manufacturing processes to control the particle size, morphology, and porosity value of the artificial bone tissue. Actual results from clinical examinations on patients were compared with their findings and it showed that the fracture pattern was accurately similar to the analysis. Then, the result of the study indicated that biomechanical researcher can use FEA method for better understanding of the fracture patterns in the biomimetic parts.[35],[36],[37],[38],[39],[40] Consequently, the FEA performed exceptionally well in predicting bone response to mechanical forces. In addition, the FEA can be employed in the surgical treatment plans, testing surgical equipment, scaffold design, and structural tissue engineering. The ultimate result of the model indicated that the designed porous structure as well as the model used for the FEA, could predict the behavior of the reinforced CS bio-nanocomposite, just in case the analytical models weren’t competent enough to describe the microstructure reaction of the materials.[45]{Figure 5}{Figure 6}{Figure 7}

 Conclusion



In the current work, the experimental evaluation was compared with the Abaqus simulation results due to its simplicity and its low-cost methods without fabrication of porous composite architecture for cancerous bone approaches. The results of this study are as follows:Fabrication of novel CS scaffold reinforced with MNPs coated with gentamicin drug using NaCl microparticles with space holder technique was successfully performed.The obtained results from elastic modulus of the porous scaffolds were 60 MPa to 145 MPa with nanocrystalline sized between 45 to 92 nm.The pH changes show that the prepared samples have no toxicity reaction in SBF and PBS saline after 28 days.The scaffolds were coated with gelatin-gentamicin drug for enhancing the biological and chemical stability of the porous scaffold in the biological environment.The micromechanical model shows a proper model for fabricated sample using space holder with suitable elastic modulus corresponding to various porosity percentages.The sample with 10 wt% MNPs had the highest solubility compared to the other sample, however; it has the maximum hyperthermia reaction in the magnetic field.As the chewing power varies differently with respect to the manipulation, the treatment plan needs to be considered.The obtained results indicated that as the MNPs size increased, it can be concluded that the maximum nonlinear frequencies are dependent on the scaffold architecture such as its porous morphology shapes and its cavities.

Acknowledgements

We acknowledge Toxicology Research Center, AJA University of Medical Sciences for their kind support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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26Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity? Biomats 2006;27:2907-15.
27Zhuang QW, Zhang ZY, Liu GL, Fu ST, He Y. Transforming growth factor-β1/Smad/connective tissue growth factor axis: the main pathway in radiation-induced fibrosis of osteoradionecrosis? Dent Hypotheses 2013;4:122.
28Monfared RM, Ayatollahi MR, Isfahani RB. Synergistic effects of hybrid MWCNT/nanosilica on the tensile and tribological properties of woven carbon fabric epoxy composites. Theor Appl Fract Mec 2018;96:272-84.
29Barbaz-I R. Experimental determining of the elastic modulus and strength of composites reinforced with two nanoparticles . Doctoral dissertation, MSc Thesis 2014, School of Mechanical Engineering Iran University of Science and Technology, Tehran, Iran.
30Zhang X, Zhou X, Hu D. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium. Dent Hypoth 2013;4:118.
31Najafinezhad A, Abdellahi M, Ghayour H, Soheily A, Chami A, Khandan A. A comparative study on the synthesis mechanism, bioactivity and mechanical properties of three silicate bioceramics. Mat Sci Eng C-Mater 2017;72:259-67.
32Meraji N, Bolhari B, Sefideh MR, Niavarzi S. Prevention of tooth discoloration due to calcium-silicate cements: a review. Dent Hypotheses 2019;10:4.
33Kordjamshidi A, Saber-Samandari S, Nejad MG, Khandan A. Preparation of novel porous calcium silicate scaffold loaded by celecoxib drug using freeze drying technique: fabrication, characterization and simulation. Ceram Int 2019;45:14126-35.
34Khazaei M, Bozorgi A, Khazaei S, Khademi A. Stem cells in dentistry, sources, and applications. Dent Hypoth 2016;7:42.
35Abdellahi M, Najafinezhad A, Ghayour H, Saber-Samandari S, Khandan A. Preparing diopside nanoparticle scaffolds via space holder method: Simulation of the compressive strength and porosity. J Mech Behav Biomed 2017;72:171-81.
36Yuan GH, Yang GB, Wu LA, Chen Z, Chen S. Potential role of dentin sialoprotein by inducing dental pulp mesenchymal stem cell differentiation and mineralization for dental tissue repair. Dent Hypotheses 2010;1:69.
37Sharafabadi AK, Abdellahi M, Kazemi A, Khandan A, Ozada N. A novel and economical route for synthesizing akermanite (Ca2MgSi2O7) nano-bioceramic. Materials Science and Engineering: C 2017;71:1072-8.
38Esmaeili S, Aghdam HA, Motififard M, Saber-Samandari S, Montazeran AH, Bigonah M, Khandan A. A porous polymeric–hydroxyapatite scaffold used for femur fractures treatment: fabrication, analysis, and simulation. European J Orthop Surg Tra 2020;30:123-31.
39Razmjooee K, Saber-Samandari S, Keshvari H, Ahmadi S. Improving anti thrombogenicity of nanofibrous polycaprolactone through surface modification. J Biomater Appl 2019;34:408-18.
40Sahmani S, Khandan A, Esmaeili S, Saber-Samandari S, Nejad MG, Aghdam MM. Calcium phosphate-PLA scaffolds fabricated by fused deposition modeling technique for bone tissue applications: fabrication, characterization and simulation. Ceram Int 2020;46:2447-56.
41Nassireslami E, Ajdarzade M. Gold coated superparamagnetic iron oxide nanoparticles as effective nanoparticles to eradicate breast cancer cells via photothermal therapy. Adv Pharm Bull 2018;8:201.
42Kabartai F, Al Homsi A, Hoffmann T. A possible explanation for tissue separation observed in histological sections after regenerative periodontal therapy. Dent Hypotheses 2017;8:23.
43Aghdam HA, Sanatizadeh E, Motififard M, Aghadavoudi F, Saber-Samandari S, Esmaeili S, Khandan A. Effect of calcium silicate nanoparticle on surface feature of calcium phosphates hybrid bio-nanocomposite using for bone substitute application. Powder Technol 2019;361:917-29
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45Rice RW. Extension of the exponential porosity dependence of strength and elastic moduli. J Am Ceram Soc 1976;59:536-7.
46Elvira C, Mano JF, San Roman J, Reis RL. Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems. Biomats 2002;23:1955-66.
47Joneidi Yekta H, Shahali M, Khorshidi S, Rezaei S, Montazeran AH, Samandari S, Khandan A. Mathematically and experimentally defined porous bone scaffold produced for bone substitute application. Nanomed J 2018;5:227-34.