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Design of Bio-Nanocomposite Scaffolds with Enhanced Properties for Bone Implantation: Fabrication, Characterization, and Simulation Saeid Sahmani and Amirsalar Khandan Contents Introduction ....................................................................................... 2 Materials and Methods ........................................................................... 3 Results and Discussion ........................................................................... 5 Conclusion ........................................................................................ 9 References ........................................................................................ 10 Abstract In the current investigation, the microarchitecture of bio-nanocomposite scaffolds fabricated by natural hydroxyapatite (n-HA) composed with copper oxide (CuO) nanoparticles and magnesium oxide (MgO) in different weight fractions, which are manufactured for the rst time by the space holder technique using NaCl particles. After that, the bio-nanocomposite scaffolds are coated with the gelatin- ibuprofen drug via a dip coating technology. The biological and mechanical experiments are performed on the samples corresponding to apatite formation, biodegradability, hardness, elastic modulus, porosity, and rate of the drug release in the phosphate buffer saline and simulated body uid (SBF). The phase composition, microstructure, physical, and cytobiological characteristics are also examined using X-ray diffraction (XRD) and scan electron microscopy (SEM). The obtained results indicate that addition of CuO nanoparticles to n-HA scaffold leads to enhance the hardness, elastic modulus, apatite formation, porosity, and roughness of the fabricated bio-nanocomposites, while its biodeg- radation rate, wettability, and drug release decrease. It is found that the prepared S. Sahmani (*) School of Science and Technology, The University of Georgia, Tbilisi, Georgia e-mail: [email protected]; [email protected] A. Khandan New Technologies Research Center, Amirkabir University of Technology, Tehran, Iran © Springer Nature Switzerland AG 2020 C. M. Hussain, S. Thomas (eds.), Handbook of Polymer and Ceramic Nanotechnology , https://doi.org/10.1007/978-3-030-10614-0_22-1 1

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Page 1: Design of Bio-Nanocomposite Scaffolds with Enhanced ... · 2 S. Sahmani and A. Khandan mechanical behavior of bio-nanocomposite scaffolds including copper oxide (CuO) nanoparticles

Design of Bio-Nanocomposite Scaffoldswith Enhanced Properties for BoneImplantation: Fabrication, Characterization,and Simulation

Saeid Sahmani and Amirsalar Khandan

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Abstract

In the current investigation, the microarchitecture of bio-nanocomposite scaffoldsfabricated by natural hydroxyapatite (n-HA) composed with copper oxide (CuO)nanoparticles and magnesium oxide (MgO) in different weight fractions, whichare manufactured for the first time by the space holder technique using NaClparticles. After that, the bio-nanocomposite scaffolds are coated with the gelatin-ibuprofen drug via a dip coating technology. The biological and mechanicalexperiments are performed on the samples corresponding to apatite formation,biodegradability, hardness, elastic modulus, porosity, and rate of the drug releasein the phosphate buffer saline and simulated body fluid (SBF). The phasecomposition, microstructure, physical, and cytobiological characteristics arealso examined using X-ray diffraction (XRD) and scan electron microscopy(SEM). The obtained results indicate that addition of CuO nanoparticles ton-HA scaffold leads to enhance the hardness, elastic modulus, apatite formation,porosity, and roughness of the fabricated bio-nanocomposites, while its biodeg-radation rate, wettability, and drug release decrease. It is found that the prepared

S. Sahmani (*)School of Science and Technology, The University of Georgia, Tbilisi, Georgiae-mail: [email protected]; [email protected]

A. KhandanNew Technologies Research Center, Amirkabir University of Technology, Tehran, Iran

© Springer Nature Switzerland AG 2020C. M. Hussain, S. Thomas (eds.), Handbook of Polymer and Ceramic Nanotechnology,https://doi.org/10.1007/978-3-030-10614-0_22-1

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bio-nanocomposite scaffolds show an excellent antibacterial response. The scaf-fold sample containing 15 wt% CuO nanoparticles represents better agreement inserving as bone graft for the cancer disease treatment. It is also observed that thepresence of magnesium ions leads to reduce the crystallinity of HA about 30–100 nm due to entering MgO nanoparticles into the network. The results related tothe sample with 10 wt% MgO nanoparticles indicate that the microscopic struc-ture of the fabricated bio-nanocomposite scaffold is three-dimensional withporous architecture.

Keywords

Drug delivery · Biomaterials · Scaffold · Dip coating technology · Space holdertechnique · Composite materials

Introduction

With the aid of rapid development in materials science and technology usingadvanced manufacturing techniques, nanocomposite materials have attracted theattention of researchers significantly in recent years. Consequently, several investi-gations have been conducted to analyze different mechanical behavior of structuresmade of such interesting composite material (Sahmani and Aghdam 2017a, b, c, d, e,f, g, h, i, 2018a, b, c, d, 2019a, b; Salama 2017; Sahmani and Fattahi 2017a, b, c, d,2018; Arat and Uyanik 2017; Zeynabad et al. 2017; Sahmani et al. 2017, 2018a, b, c,2019a, b, c, d, e, f, g, 2020a, b; Fattahi and Sahmani 2017; Tang et al. 2017; Deyabet al. 2018; Kadi et al. 2018; Xu et al. 2018; Sarafraz et al. 2019, 2020; Jalili et al.2019; Sahmani and Khandan 2019; Fattahi et al. 2019; Narayanasamy et al. 2019;Lee et al. 2019; Sahmani and Safaei 2019a, b; Li et al. 2019; Sahmani and Madyira2019; Yang et al. 2020).

On the other hand, the addition of copper, zinc, or manganese can enhance thebone remodeling capability of biomaterials. In general, the use of biomaterials is thereplacement and substitution of organs that have lost their efficiency due to illness orinjury. One of the most widely used biomaterial is hydroxyapatite with a chemicalcomposition of Ca10(PO4)6(OH)2, the mechanical properties of which can beenhanced by compositing medical biomaterials in the field of medical engineeringfor specific applications in medicine. Other examples include deposition of copper,gold, and iron that contain bacteria.

With the aid of material science technology, nanoscale biological compoundshave unique chemical-mechanical properties. In recent years, the efficacy of severalclasses of antimicrobial nanoparticles has demonstrated which can be utilized as aneffective way for treatment of infectious diseases (Yan et al. 2018; Hickey et al.2015; Sahmani et al. 2018d, e). This chapter examines the recent efforts ofresearchers to identify and treat infectious diseases using antimicrobial nanoparticlesand pharmaceutical nanomaterials. The purpose of this chapter is to provide infor-mation on the mechanical performance, biological response, simulation of the some

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mechanical behavior of bio-nanocomposite scaffolds including copper oxide (CuO)nanoparticles and coated by gelatin-ibuprofen thin layer for using in drug deliverysystems. Previously, it has been shown that CuO nanoparticles at high concentra-tions exhibit a high incidence of amine and carboxyl groups in the Bacillus subtilisbacteria compared to silver nanoparticles, thus exhibiting more antibacterial activity.Copper deficiency (hypocupremia) is commonly seen in patients with nephrosis(kidney failure). Also, Copper is a strong antioxidant, eliminating free radicals andpreventing cell damage. It also seems to have anticancer effects.

Furthermore, metallic and nonmetallic oxide nanoparticles are very valuablebecause of their high application rates in biomedical tools. Among the metallicoxide nanoparticles, magnesium oxide (MgO) is one of those materials that areextensively utilized for clinical applications in laboratories and clinical approaches,such as the use of ceramic powder, composite dielectric materials, osteoporosis,bone loss, bone fractures complications, and biomedical devices (Sahmani et al.2018f, g, h, 2019h, i, 2020c; Vukajlovic et al. 2019). The MgO nanoparticle can alsobe employed as an additive or reinforcement for polymers, ceramics, and metals withcorrective effect. In recent years, efforts have been performed to develop the bindingof host and guest artificial tissues. Calcium phosphate (CaP) is an important mineralmaking the hard component of tissues such as bones, teeth, and tendons that givesthese organs stability, strength and improves their mechanical and chemicalperformance.

Different ions such as magnesium, sodium, carbonate, fluorine, etc., are effectivefor the biophysical behavior of the bone. The biophysical properties such as thevolume of magnesium, size of crystals and nanoparticles are important for bonesubstitution to improve biocompatibility, bioactivity, and mechanical properties withthe highest similarity to the chemical composition of the body HA that result insignificant shortening in time of a treatment. In the current study, with the aid of theX-ray diffraction (XRD) and scan electron microscopy (SEM) equipped with theenergy dispersive spectroscopy (EDS), the mechanical as well as biological charac-teristics of the fabricated HA-MgO and HA-CuO bio-nanocomposite scaffolds withGN-IBO surface coating and containing various MgO and CuO weight fractions areinvestigated. Based upon the extracted mechanical properties, a sandwich platemodel is developed to study analytically the vibration response of an axially loadedplate-type bone implant made of the produced HA-MgO and HA-CuObio-nanocomposites. Moreover, the bioactivity, degradation rate, and wettability ofthe manufactured scaffolds are anticipated experimentally.

Materials and Methods

In the current study, at first the natural hydroxyapatite (n-HA) particles are createdfrom a natural source of bovine bone. The bovine is boiled and heated at 1000C forseveral hours and then milled for 10 h. To prevent the formation of soot in thematerial during heating, the bones are cut into small pieces with saws and thenburned in the air for 3 h with a torch up to about 400 �C. The resulting powder is then

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subjected to heat treatment at 800–850 �C for 3 h. The ball to powder ratio (BPR) is10:1 for the high energy ball milling (HEBM) process. Then, the milled powders areplaced in a temperature of 800 �C for 24 h to dry up the moisture. After that,appropriate amounts of CuO nanoparticles are mixed with the n-HA using themixer corresponding to 0, 5, 10, and 15 wt%. CuO weight fractions. Figure 1a–iillustrates SEM photos and the related analyses for different parts of the n-HA-CuObio-nanocomposites.

To produce the scaffold structure, the space holder technique is put to use. To thisend, the bio-nanocomposites are mixed with 65–70% NaCl particles and thenpressed under 120–160 MPa pressure using sunflower oil and steel die. In order toobtain a homogeneous mixture together with edible liquid oil (2 wt%. Of homoge-nized powder), a cubic matrix with 14� 15 mm2 surface area under pressure of 120–160 MPa 1100 �C is employed, which results in a sample with 14 � 15 � 6 mm3

dimensions. Subsequently, the bulk samples are inserted into a furnace with 1100 �Ctemperature to eliminate the NaCl particles.

Fig. 1 SEM image of (a) n-HA pure powder, (b) CuO nanoparticles, (c) bio-nanocompositescaffold with 15 wt% CuO and IBO-GN film, (d) XRD pattern of n-HA-CuObio-nanocomposites containing various amount of CuO nanoparticles, (e) CuO, (f) drug releasein the sample with 15 wt% CuO, (g) EDS images of the sample with 15 wt% CuO that precipitateapatite on it, (h) cell growth in the sample holes, (i) fabricated samples coated with GN-IBO

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In this study, 10 grams of gelatin (GN) powder is dissolved in 100 ml hot waterfor 2 h in a hot plate stirrer at 60 �C with 1000 rpm. The GN-loaded ibuprofen (IBO)polymer solution is then obtained for ceramic coating of the fabricated scaffolds. Forthis purpose, the scaffolds are coated/soaked with 85% GN diffused IBO solutionusing dip coating technique, which results in to immerse the bio-nanocompositescaffolds in the polymer solution for 30 seconds. In order to achieve a uniformcoating areas and extrapolation of the polymer solution, the specimens are placed inan aluminum foil and then centrifuged at 500 rpm for a duration of 30 seconds. Thefinal samples are then kept in the oven in the 80 �C temperature to increase itscompact. Finally, the specimens are placed in a vacuum oven for 24 h to dry.

Preliminary in vitro and mechanical experiments are conducted for wettingproperties, bone apatite formation, biodegradation rate, and rate of drug releasefrom the samples into the simulated body fluid (SBF) and phosphate buffer salineproduced based on the Kokubo procedure. It is demonstrated that the enhancedbio-nanocomposite scaffolds coated by GN-IBO have the capability to promote celladhesion and proliferation with superior biocompatibility and bioactivity. The totalporosity of the bio-nanocomposite scaffolds coated with GN-IBO is measured usingthe Archimedes principle. Also, in order to evaluate the nanoparticle morphologyand porosity structure (shape, size, and relevance), the scanning electron microscopy(XL30 Philips, SEM) with 30–40 kV voltage is employed. In addition, the compres-sive strength test is performed on the cubic specimens using SANTAMmachine. Thequantum irradiation for the presence of apatite layer is performed using elementalanalysis with X-ray energy dissipation (EDS). In order to investigate the structuraland phase studies, X-ray diffraction (XRD, Philips x, pert) Cu Ka radiation isutilized.

Results and Discussion

In accordance with Fig. 2, it is revealed that the bio-nanocomposite scaffolds madeof n-HA-CuO with 0, 5, 10, 15 wt% display the compressive strength value of0.8 MPa for the sample containing the minimum amount of CuO and 1.4 � 0.3 MPafor the sample with the highest amount of CuO nanoparticles. It is observed that byadding the GN-IBO coating, the compressive strength of samples enhances. Theobtained results for the fractured samples indicate that the microcracks occur withinthe strut walls. So, one can say that the fracture in the bio-nanocomposite scaffoldshappens near to unidirectional pores, with several types of debris segregated fromthe surface of the specimens. The surface analysis via SEM shows that the GN-IBOcoated surfaces have no distributed debris due to the larger fracture strain of thepolymer compared to a noncoated surface. It means that the intrinsic behavior of theGN-IBO coating layer may restrain cracks propagation, providing better fracturetoughness.

According to Fig. 2, it is found that adding CuO nanoparticles to n-HA matrixleads to increase the hardness and the elastic modulus of all samples. Moreover, theantibacterial response under UV indicates that that bacteria have absorption and bind

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with the surface in the sample without CuO nanoparticles. Therefore, the addition ofCuO leads to better antibacterial surface for the samples.

Fig. 2a depicts that the hardness and the elastic modulus of thebio-nanocomposite scaffold increases through addition the CuO nanoparticles. TheYoung’s modulus of the n-HA ceramic changes between 250 and 300 MPadepending on the porosity and impurities. Additionally, the scaffold substance pre-sents super-esthetic features between 900 and 1100 �C. The fracture toughness of thescaffolds enhances linearly through increasing the porosity. Because in reality, theporosity of the artificial implanted bone increases after implantation over time as thebone grows.

Fig. 2b displays that the bone formation increases and the biodegradation ratedecreases for higher amount of CuO nanoparticles added to the n-HA powder. TheEDS analysis reveals that the new white layer precipitate on the free surface ofscaffolds contains high amount of Calcium and phosphor which is below 2 and Ca/Pis almost 1.7 which is close to human bone formation. On the other hand, Fig. 2cindicates that over time, water molecules are absorbed on the free surface of scaf-folds that causes to increase the penetration rate of the tip of the cracks. It is observedthat through addition of CuO nanoparticles, the porosity increases while the drug

Fig. 2 Analysis result for (a) the hardness vs. elastic modulus, (b) apatite formationvs. biodegradation rate, (c) porosity value vs. drug release, (d) contact angle vs. wetting propertiesof n-HA-CuO scaffold bio-nanocomposite containing 0 wt%, 5 wt%, 10 wt%, and 15 wt% CuO

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release in the phosphate buffer solution detected with UV spectrum reduces. It maybe due to this fact that CuO nanoparticles prevent the surface of bio-nanocompositescaffolds to degrade easily because of higher hardness and elastic modulus of thesample with 15 wt% CuO nanoparticles.

Fig. 2d demonstrates that the wettability of the samples decreases from almost85� to 60� due to their high roughness between 25 to 50 μm. The obtained resultsindicated that the n-HA scaffold exhibits a negative charge due to the presence ofhydroxyl and phosphate groups; therefore, it is combined with positive ions ofcalcium. Calcium-rich and calcium phosphate, which is formed on a scaffoldcomposed of phosphate ions in the SBF, forms a powerful calcium phosphate thatbecomes bone apatite.

The XRD for HA-MgO samples with different weight fractions of MgO nano-particles after thermal treatment at 1100 � C for 30 min are presented in Fig. 3. It isobserved that the peaks associated with the MgO nanoparticles in the positions of 4θequal to 65–70� represent the crystalline characteristics. The two important peaks forthe XRD pattern of the fabricated HA-MgO bio-nanocomposite scaffolds withGN-IBO surface coating describe the crystalline phase at 65� planes of MgO. Thereduction in the peaks’ intensity of the HA-MgO-GN-IBO bio-nanocompositescaffold compared to those of the pure MgO and HA may be related to the reductionin degree of crystallization of the scaffolds with respect to the amorphous GNaggregate. The results indicate that the glass-ceramics (HA-MgO) have biochemical

Fig. 3 Comparison of the XRD patterns for the HA-MgO bio-nanocomposite scaffolds containingdifferent weight fractions of MgO nanoparticles

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reaction that can be considered for bioactive characteristics with mechanical prop-erties better than CaPs.

In Fig. 4a–d, it is shown that the HA-MgO bio-nanocomposite scaffold withGN-IBO surface coating has mountainous surfaces with low porosity. It is found thatthe mean pore size for the bio-nanocomposite scaffolds is equal to 50 μm. The resultsrelated to the elemental analysis of the HA-MgO-GN-IBO scaffolds with 5 wt%,10 wt%, and 15 wt%MgO nanoparticles presented in Fig. 5a–c confirm the presenceof calcium, phosphorus, and Si elements on the free surface of them. By comparingthe elemental analyses associated with the HA-MgO and HA-MgO-GN-IBO scaf-folds, the presence of Mg element’s peaks in the image of the elemental analysis ofHA-MgO-GN-IBO scaffold is clearly obvious.

GN loaded with IBO has excellent wettability which results in high elasticity andgood biocompatibility property. Therefore, thin type of surface coating is similar tothat synthetic polymers with normal body tissues architecture. On the other hand, thesuccess of a biomaterial depends on the degree of biocompatibility and its intrinsicbehavior beside bioceramic. Many factors affect the biocompatibility of a substance,and the examination shows that GN is biocompatible, bioactive and can enhance thechemical and mechanical performance of the calcium phosphates porous scaffolds.

Fig. 4 (a) SEM image of the fabricated sample containing 10 wt% MgO nanoparticles afterimmersion in SBF including thick layer of apatite (b) Magnified SEM image of the samplecontaining 10 wt% MgO nanoparticles sample, (c) SEM image of the sample soaked in the PBS

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As shown in Fig. 5a–b, it is observed that the increment in the amount of additiveMgO nanoparticles in the HA leads to increase its bioactivity as it is visible in theSEM micrographs. This increase has two reasons: first, reducing the HA amountresults in an increase in ion groups within the bio-nanocomposite microstructure, somore ionic connections between the microstructure and the SBF solution occur.Secondly, by decreasing the weight fraction of HA, the porosity increases.

Conclusion

In this work, the hierarchically mechanical and biological characteristics of fabri-cated HA-CuO and HA-MgO bio-nanocomposite scaffolds coated by GN-IBO filmwere predicted. It was found that by adding the GN-IBO coating, the compressivestrength of samples enhances. It was revealed that the bone formation increases andthe biodegradation rate decreases for higher amount of CuO nanoparticles added tothe n-HA powder. The EDS analysis indicated that the new white layer precipitate onthe scaffolds contains high amount of calcium and phosphor which is close to humanbone formation.

It was indicated that adding CuO nanoparticles to n-HA matrix leads to increasethe hardness and the elastic modulus of all samples. Moreover, the antibacterialresponse under UV indicates that that bacterial have absorption and bind with thesurface in the sample without CuO nanoparticles. Therefore, the addition of CuOleads to better antibacterial surface for the samples. It was observed that the boneformation increases and the biodegradation rate decreases for higher amount of CuOnanoparticles added to the n-HA powder. The EDS analysis reveals that the newwhite layer precipitate on the free surface of scaffolds contains high amount ofCalcium and phosphor which is below 2 and Ca/P is almost 1.7 which is close tohuman bone formation.

Fig. 5 (a) Bone-like apatite formation in SBF vs. biodegradation rate in PBS, (b) the wettability inSBF vs. the surface roughness plots of the manufactured samples coated with GN-IBO associatedwith different weight fractions of MgO nanoparticles

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The presence of calcium, phosphorus, and Si elements on the free surface ofHA-MgO bio-nanocomposite scaffolds was confirmed. By comparing the elementalanalyses associated with the HA-MgO and HA-MgO-GN-IBO scaffolds, the pres-ence of Mg element’s peaks in the image of the elemental analysis of HA-MgO-GN-IBO scaffold was clearly obvious. Moreover, it was demonstrated that the incrementin the amount of additive MgO nanoparticles in the HA leads to increase itsbioactivity as it is visible in the SEM micrographs. This increase has two reasons:first, reducing the HA amount results in an increase in ion groups within thebio-nanocomposite microstructure, so more ionic connections between the micro-structure and the SBF solution occur. Secondly, by decreasing the weight fraction ofHA, the porosity increases.

References

Arat R, Uyanik N (2017) Study of the morphological and thermal properties of polystyrenenanocomposites based on modified halloysite nanotubes with styrene-maleic anhydride copol-ymers. Mater Today Commun 13:255–262

Deyab MA, Hamdi N, Lachkar M, El Bali B (2018) Clay/phosphate/epoxy nanocomposites forenhanced coating activity towards corrosion resistance. Prog Org Coat 123:232–237

Fattahi AM, Sahmani S (2017) Size dependency in the axial postbuckling behavior of nanopanelsmade of functionally graded material considering surface elasticity. Arab J Sci Eng 42:4617–4633

Fattahi AM, Sahmani S, Ahmed NA (2019) Nonlocal strain gradient beam model for nonlinearsecondary resonance analysis of functionally graded porous micro/nano-beams under periodichard excitations. Mech Based Des Struct Mach. https://doi.org/10.1080/15397734.2019.1624176

Hickey DJ, Ercan B, Sun L, Webster TJ (2015) Adding MgO nanoparticles to hydroxyapatite–PLLA nanocomposites for improved bone tissue engineering applications. Acta Biomater14:175–184

Jalili MA, Allafchian A, Karimzadeh F, Nasiri F (2019) Synthesis and characterization of magne-tite/Alyssum homolocarpum seed gum/Ag nanocomposite and determination of its antibacterialactivity. Int J Biol Macromol 139:1263–1271

Kadi MW, Ismail AA, Mohamed RM, Bahnemann DW (2018) Photodegradation of the herbicideimazapyr over mesoporous In2O3-TiO2 nanocomposites with enhanced photonic efficiency. SepPurif Technol 205:66–73

Lee SY, Lee G, Jun Y-S, Park YI (2019) Visible/near-infrared driven highly efficient photocatalystbased on upconversion nanoparticles/g-C3N4 nanocomposite. Appl Surf Sci 508:144839

Li Q, Luo S, Wang Y, Wang Q-M (2019) Carbon based polyimide nanocomposites thin film strainsensors fabricated by ink-jet printing method. Sensors Actuators A Phys 300:111664

Narayanasamy M, Kirubasankar B, Joseph A, Yan C, Angaiah S (2019) Influence of pulse reversecurrent on mechanical and corrosion resistance properties of Ni-MoSe2 nanocomposite coat-ings. Appl Surf Sci 493:225–230

Sahmani S, Aghdam MM (2017a) Size dependency in axial postbuckling behavior of hybrid FGMexponential shear deformable nanoshells based on the nonlocal elasticity theory. Compos Struct166:104–113

Sahmani S, AghdamMM (2017b) Imperfection sensitivity of the size-dependent postbuckling responseof pressurized FGM nanoshells in thermal environments. Arch Civ Mech Eng 17:623–638

Sahmani S, Aghdam MM (2017c) Size-dependent axial instability of microtubules surrounded bycytoplasm of a living cell based on nonlocal strain gradient elasticity theory. J Theor Biol422:59–71

10 S. Sahmani and A. Khandan

Page 11: Design of Bio-Nanocomposite Scaffolds with Enhanced ... · 2 S. Sahmani and A. Khandan mechanical behavior of bio-nanocomposite scaffolds including copper oxide (CuO) nanoparticles

Sahmani S, Aghdam MM (2017d) Nonlinear instability of axially loaded functionally gradedmultilayer graphene platelet-reinforced nanoshells based on nonlocal strain gradient elasticitytheory. Int J Mech Sci 131:95–106

Sahmani S, Aghdam MM (2017e) A nonlocal strain gradient hyperbolic shear deformable shellmodel for radial postbuckling analysis of functionally graded multilayer GPLRC nanoshells.Compos Struct 178:97–109

Sahmani S, Aghdam MM (2017f) Nonlocal strain gradient beam model for nonlinear vibration ofprebuckled and postbuckled multilayer functionally graded GPLRC nanobeams. Compos Struct179:77–88

Sahmani S, Aghdam MM (2017g) Axial postbuckling analysis of multilayer functionally gradedcomposite nanoplates reinforced with GPLs based on nonlocal strain gradient theory. Eur PhysJ Plus 132:490

Sahmani S, AghdamMM (2017h) Size-dependent nonlinear bending of micro/nano-beams made ofnanoporous biomaterials including a refined truncated cube cell. Phys Lett A 381:3818–3830

Sahmani S, Aghdam MM (2017i) Nonlinear vibrations of pre-and post-buckled lipid supramolec-ular micro/nano-tubules via nonlocal strain gradient elasticity theory. J Biomech 65:49–60

Sahmani S, Aghdam MM (2018a) Nonlocal strain gradient shell model for axial buckling andpostbuckling analysis of magneto-electro-elastic composite nanoshells. Compos Part B132:258–274

Sahmani S, Aghdam MM (2018b) Nonlinear instability of hydrostatic pressurized microtubulessurrounded by cytoplasm of a living cell including nonlocality and strain gradient microsizedependency. Acta Mech 229:403–420

Sahmani S, Aghdam MM (2018c) Nonlocal strain gradient beam model for postbuckling andassociated vibrational response of lipid supramolecular protein micro/nano-tubules. Math Biosci295:24–35

Sahmani S, Aghdam MM (2018d) Nonlinear primary resonance of micro/nano-beams made ofnanoporous biomaterials incorporating nonlocality and strain gradient size dependency. ResultsPhys 8:879–892

Sahmani S, Aghdam MM (2019a) Size-dependent nonlinear mechanics of biological nanoporousmicrobeams. Nanomater Adv Biol Appl:181–207

Sahmani S, Aghdam MM (2019b) Nonlocal electrothermomechanical instability of temperature-dependent FGM nanopanels with piezoelectric facesheets. Iran J Sci Technol Trans Mech Eng43:579–593

Sahmani S, Fattahi AM (2017a) An anisotropic calibrated nonlocal plate model for biaxialinstability analysis of 3D metallic carbon nanosheets using molecular dynamics simulations.Mater Res Expr 4:065001

Sahmani S, Fattahi AM (2017b) Development an efficient calibrated nonlocal plate model fornonlinear axial instability of zirconia nanosheets using molecular dynamics simulation. J MolGraph Model 75:20–31

Sahmani S, Fattahi AM (2017c) Calibration of developed nonlocal anisotropic shear deformableplate model for uniaxial instability of 3D metallic carbon nanosheets using MD simulations.Comput Methods Appl Mech Eng 322:187–207

Sahmani S, Fattahi AM (2017d) Imperfection sensitivity of the size-dependent nonlinear instabilityof axially loaded FGM nanopanels in thermal environments. Acta Mech 228:3789–3810

Sahmani S, Fattahi AM (2018) Small scale effects on buckling and postbuckling behaviors ofaxially loaded FGM nanoshells based on nonlocal strain gradient elasticity theory. Appl MathMech 39:561–580

Sahmani S, Khandan A (2019) Size dependency in nonlinear instability of smart magneto-electro-elastic cylindrical composite nanopanels based upon nonlocal strain gradient elasticity. Micro-syst Technol 25:2171–2186

Sahmani S, Madyira DM (2019) Nonlocal strain gradient nonlinear primary resonance of micro/nano-beams made of GPL reinforced FG porous nanocomposite materials. Mech Based DesStruct Mach. https://doi.org/10.1080/15397734.2019.1695627

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Sahmani S, Safaei B (2019a) Nonlinear free vibrations of bi-directional functionally graded micro/nano-beams including nonlocal stress and microstructural strain gradient size effects. Thin-Walled Struct 140:342–356

Sahmani S, Safaei B (2019b) Nonlocal strain gradient nonlinear resonance of bi-directionalfunctionally graded composite micro/nano-beams under periodic soft excitation. Thin-WalledStruct 143:106226

Sahmani S, Aghdam MM, Bahrami M (2017) An efficient size-dependent shear deformable shellmodel and molecular dynamics simulation for axial instability analysis of silicon nanoshells.J Mol Graph Model 77:263–279

Sahmani S, Aghdam MM, Rabczuk T (2018a) Nonlinear bending of functionally graded porousmicro/nano-beams reinforced with graphene platelets based upon nonlocal strain gradienttheory. Compos Struct 186:68–78

Sahmani S, Aghdam MM, Rabczuk T (2018b) A unified nonlocal strain gradient plate model fornonlinear axial instability of functionally graded porous micro/nano-plates reinforced withgraphene platelets. Mater Res Expr 5:045048

Sahmani S, Aghdam MM, Rabczuk T (2018c) Nonlocal strain gradient plate model for nonlinearlarge-amplitude vibrations of functionally graded porous micro/nano-plates reinforced withGPLs. Compos Struct 198:51–62

Sahmani S, Saber-Samandari S, Shahali M, Yekta HJ, Aghadavoudi F, Montazeran AH, AghdamMM, Khandan A (2018d) Mechanical and biological performance of axially loaded novelbio-nanocomposite sandwich plate-type implant coated by biological polymer thin film.J Mech Behav Biomed Mater 88:238–250

Sahmani S, Saber-Samandari S, Aghdam MM, Khandan A (2018e) Nonlinear resonance responseof porous beam-type implants corresponding to various morphology shapes for bone tissueengineering applications. J Mater Eng Perform 27:5370–5383

Sahmani S, Khandan A, Saber-Samandari S, Aghdam MM (2018f) Nonlinear bending and insta-bility analysis of bioceramics composed with magnetite nanoparticles: fabrication, characteri-zation, and simulation. Ceram Int 44:9540–9549

Sahmani S, Khandan A, Saber-Samandari S, Aghdam MM (2018g) Vibrations of beam-typeimplants made of 3D printed bredigite-magnetite bio-nanocomposite scaffolds under axialcompression: application, communication and simulation. Ceram Int 44:11282–11291

Sahmani S, Shahali M, Khandan A, Saber-Samandari S, Aghdam MM (2018h) Analytical andexperimental analyses for mechanical and biological characteristics of novel nanoclaybio-nanocomposite scaffolds fabricated via space holder technique. Appl Clay Sci 165:112–123

Sahmani S, Aghdam MM, Akbarzadeh A (2019a) Surface stress effect on nonlinear instability ofimperfect piezoelectric nanoshells under combination of hydrostatic pressure and lateral electricfield. AUT J Mech Eng 2:177–190

Sahmani S, Fattahi AM, Ahmed NA (2019b) Analytical treatment on the nonlocal strain gradientvibrational response of postbuckled functionally graded porous micro-/nanoplates reinforcedwith GPL. Eng Comput. https://doi.org/10.1007/s00366-019-00782-5

Sahmani S, Fotouhi M, Aghdam MM (2019c) Size-dependent nonlinear secondary resonance ofmicro-/nano-beams made of nano-porous biomaterials including truncated cube cells. ActaMech 230:1077–1103

Sahmani S, Fattahi AM, Ahmed NA (2019d) Size-dependent nonlinear forced oscillation of self-assembled naotubules based on the nonlocal strain gradient beam model. J Braz Soc Mech SciEng 41:239

Sahmani S, Fattahi AM, Ahmed NA (2019e) Nonlinear torsional buckling and postbucklinganalysis of cylindrical silicon nanoshells incorporating surface free energy effects. MicrosystTechnol 25:3533–3546

Sahmani S, Fattahi AM, Ahmed NA (2019f) Analytical mathematical solution for vibrationalresponse of postbuckled laminated FG-GPLRC nonlocal strain gradient micro-/nanobeams.Eng Comput 35:1173–1189

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Sahmani S, Fattahi AM, Ahmed NA (2019g) Radial postbuckling of nanoscaled shells embedded inelastic foundations based on Ru’s surface stress elasticity theory. Mech Based Des Struct Mach47:787–806

Sahmani S, Saber-Samandari S, Khandan A, Aghdam MM (2019h) Nonlinear resonance investi-gation of nanoclay based bio-nanocomposite scaffolds with enhanced properties for bonesubstitute applications. J Alloys Compd 773:636–653

Sahmani S, Shahali M, Nejad MG, Khandan A, AghdamMM, Saber-Samandari S (2019i) Effect ofcopper oxide nanoparticles on electrical conductivity and cell viability of calcium phosphatescaffolds with improved mechanical strength for bone tissue engineering. Eur Phys J Plus 134:7

Sahmani S, Fattahi AM, Ahmed NA (2020a) Surface elastic shell model for nonlinear primaryresonant dynamics of FG porous nanoshells incorporating modal interactions. Int J Mech Sci165:105203

Sahmani S, Fattahi AM, Ahmed NA (2020b) Develop a refined truncated cubic lattice structure fornonlinear large-amplitude vibrations of micro/nano-beams made of nanoporous materials. EngComput 36:359–375

Sahmani S, Khandan A, Esmaeili S, Saber-Samandari S, Ghadiri Nejad M, Aghdam MM (2020c)Calcium phosphate-PLA scaffolds fabricated by fused deposition modeling technique for bonetissue applications: fabrication, characterization and simulation. Ceram Int 46:2447–2456

Salama A (2017) Dicarboxylic cellulose decorated with silver nanoparticles as sustainable anti-bacterial nanocomposite material. Environ Nanotechnol Monit Manage 8:228–232

Sarafraz A, Sahmani S, Aghdam MM (2019) Nonlinear secondary resonance of nanobeams undersubharmonic and superharmonic excitations including surface free energy effects. Appl MathModel 66:195–226

Sarafraz A, Sahmani S, Aghdam MM (2020) Nonlinear primary resonance analysis of nanoshellsincluding vibrational mode interactions based on the surface elasticity theory. Appl Math Mech41:233–260

Tang Y, Liu Q, Yang X, Wei M, Zhang M (2017) Copper oxide coated gold Nanorods like a film: afacile route to nanocomposites for electrochemical application. J Electroanal Chem 806:8–14

Vukajlovic D, Parker J, Bretcanu O, Novakovic K (2019) Chitosan based polymer/bioglasscomposites for tissue engineering applications. Mater Sci Eng C 96:955–967

Xu H, Song Y, Zhang Q, Zheng Q (2018) Contributions of silica network and interfacial fraction inreinforcement and payne effect of polypropylene glycol nanocomposites. Polymer 138:139–145

Yan Y, Zhang Y, Zuo Y, Zou Q, Li J, Li Y (2018) Development of Fe3O4–HA/PU super-paramagnetic composite porous scaffolds for bone repair application. Mater Lett 212:303–306

Yang X, Sahmani S, Safaei B (2020) Postbuckling analysis of hydrostatic pressurized FGMmicrosized shells including strain gradient and stress-driven nonlocal effects. Eng Comput.https://doi.org/10.1007/s00366-019-00901-2

Zeynabad FB, Salehi R, Mahkam M (2017) Design of pH-responsive antimicrobial nanocompositeas dual drug delivery system for tumor therapy. Appl Clay Sci 141:23–35

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