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  1. Pahlevanzadeh F, Bakhsheshi-Rad HR, Hamzah E
    J Mech Behav Biomed Mater, 2018 06;82:257-267.
    PMID: 29627737 DOI: 10.1016/j.jmbbm.2018.03.016
    In this study, a bone cement consisting of poly methyl methacrylate (PMMA)-poly caprolactone (PCL)-fluorapatite (FA)-graphene oxide (GO) was synthesized as bone filler for application in orthopedic surgeries. The FA and GO particulates were homogenously distributed in the PMMA-PCL polymer matrix and no defects and agglomeration were found in the PMMA-PCL/FA/GO bone cement. The in-vitro bioactivity result exhibited that addition of FA and GO to the polymer cement (PMMA-PCL) improved the apatite formation ability on the surface of polymer. The results also showed that addition of FA to the polymer bone cement escalated the compressive strength and elastic modulus while reducing elongation to 8 ± 2%. However, after addition of GO into the PMMA-PCL/FA bone cement, both compressive strength and elongation considerably increased to 101 ± 5 MPa and 35 ± 6%, respectively. Furthermore, tensile tests exhibited that inclusion of GO was favorable in improving the tensile modulus, UTS and elongation of the PMMA-PCL/FA bone cement. The cytotoxicity test pointed out that MG63 osteoblast cells viability increased to 279 ± 15% after addition of FA and GO to the PMMA-PCL polymer bone cement. The DAPI (4',6-diamidino-2-phenylindole) staining demonstrated better spreading and attachment of MG63 cells on PMMA-PCL/FA/GO surface compared to the PMMA-PCL bone cements. These results confirm the suitable mechanical properties and favorable bioactivity along with high cells viability of PMMA-PCL/FA/GO bone cement, indicating its potentials for orthopedic applications.
  2. Saud SN, Hamzah E, Bakhsheshi-Rad HR, Abubakar T
    Scanning, 2017;2017:1789454.
    PMID: 29109802 DOI: 10.1155/2017/1789454
    The influence of Ta additions on the microstructure and properties of Cu-Al-Ni shape memory alloys was investigated in this paper. The addition of Ta significantly affects the green and porosity densities; the minimum percentage of porosity was observed with the modified prealloyed Cu-Al-Ni-2.0 wt.% Ta. The phase transformation temperatures were shifted towards the highest values after Ta was added. Based on the damping capacity results, the alloy of Cu-Al-Ni-3.0 wt.% Ta has very high internal friction with the maximum equivalent internal friction value twice as high as that of the prealloyed Cu-Al-Ni SMA. Moreover, the prealloyed Cu-Al-Ni SMAs with the addition of 2.0 wt.% Ta exhibited the highest shape recovery ratio in the first cycle (i.e., 100% recovery), and when the number of cycles is increased, this ratio tends to decrease. On the other hand, the modified alloys with 1.0 and 3.0 wt.% Ta implied a linear increment in the shape recovery ratio with increasing number of cycles. Polarization tests in NaCl solution showed that the corrosion resistance of Cu-Al-Ni-Ta SMA improved with escalating Ta concentration as shown by lower corrosion current densities, higher corrosion potential, and formation of stable passive film.
  3. Bakhsheshi-Rad HR, Hamzah E, Kasiri-Asgarani M, Jabbarzare S, Iqbal N, Abdul Kadir MR
    Mater Sci Eng C Mater Biol Appl, 2016 Mar;60:526-537.
    PMID: 26706560 DOI: 10.1016/j.msec.2015.11.057
    The present study addressed the synthesis of a bi-layered nanostructured fluorine-doped hydroxyapatite (nFHA)/polycaprolactone (PCL) coating on Mg-2Zn-3Ce alloy via a combination of electrodeposition (ED) and dip-coating methods. The nFHA/PCL composite coating is composed of a thick (70-80 μm) and porous layer of PCL that uniformly covered the thin nFHA film (8-10 μm) with nanoneedle-like microstructure and crystallite size of around 70-90 nm. Electrochemical measurements showed that the nFHA/PCL composite coating presented a high corrosion resistance (R(p)=2.9×10(3) kΩ cm(2)) and provided sufficient protection for a Mg substrate against galvanic corrosion. The mechanical integrity of the nFHA/PCL composite coatings immersed in SBF for 10 days showed higher compressive strength (34% higher) compared with the uncoated samples, indicating that composite coatings can delay the loss of compressive strength of the Mg alloy. The nFHA/PCL coating indicted better bonding strength (6.9 MPa) compared to PCL coating (2.2 MPa). Immersion tests showed that nFHA/PCL composite-coated alloy experienced much milder corrosion attack and more nucleation sites for apatite compared with the PCL coated and uncoated samples. The bi-layered nFHA/PCL coating can be a good alternative method for the control of corrosion degradation of biodegradable Mg alloy for implant applications.
  4. Abazari S, Shamsipur A, Bakhsheshi-Rad HR, Ismail AF, Sharif S, Razzaghi M, et al.
    Materials (Basel), 2020 Oct 04;13(19).
    PMID: 33020427 DOI: 10.3390/ma13194421
    In recent years considerable attention has been attracted to magnesium because of its light weight, high specific strength, and ease of recycling. Because of the growing demand for lightweight materials in aerospace, medical and automotive industries, magnesium-based metal matrix nanocomposites (MMNCs) reinforced with ceramic nanometer-sized particles, graphene nanoplatelets (GNPs) or carbon nanotubes (CNTs) were developed. CNTs have excellent material characteristics like low density, high tensile strength, high ratio of surface-to-volume, and high thermal conductivity that makes them attractive to use as reinforcements to fabricate high-performance, and high-strength metal-matrix composites (MMCs). Reinforcing magnesium (Mg) using small amounts of CNTs can improve the mechanical and physical properties in the fabricated lightweight and high-performance nanocomposite. Nevertheless, the incorporation of CNTs into a Mg-based matrix faces some challenges, and a uniform distribution is dependent on the parameters of the fabricating process. The characteristics of a CNTs reinforced composite are related to the uniform distribution, weight percent, and length of the CNTs, as well as the interfacial bonding and alignment between CNTs reinforcement and the Mg-based matrix. In this review article, the recent findings in the fabricating methods, characterization of the composite's properties, and application of Mg-based composites reinforced with CNTs are studied. These include the strategies of fabricating CNT-reinforced Mg-based composites, mechanical responses, and corrosion behaviors. The present review aims to investigate and conclude the most relevant studies conducted in the field of Mg/CNTs composites. Strategies to conquer complicated challenges are suggested and potential fields of Mg/CNTs composites as upcoming structural material regarding functional requirements in aerospace, medical and automotive industries are particularly presented.
  5. Dayaghi E, Bakhsheshi-Rad HR, Hamzah E, Akhavan-Farid A, Ismail AF, Aziz M, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Sep;102:53-65.
    PMID: 31147024 DOI: 10.1016/j.msec.2019.04.010
    Recently, porous magnesium and its alloys are receiving great consideration as biocompatible and biodegradable scaffolds for bone tissue engineering application. However, they presented poor antibacterial performance and corrosion resistance which limited their clinical applications. In this study, Mg-Zn (MZ) scaffold containing different concentrations of tetracycline (MZ-xTC, x = 1, 5 and 10%) were fabricated by space holder technique to meet the desirable antibacterial activity and corrosion resistance properties. The MZ-TC contains total porosity of 63-65% with pore sizes in the range of 600-800 μm in order to accommodate bone cells. The MZ scaffold presented higher compressive strength and corrosion resistance compared to pure Mg scaffold. However, tetracycline incorporation has less significant effect on the mechanical and corrosion properties of the scaffolds. Moreover, MZ-xTC scaffolds drug release profiles show an initial immediate release which is followed by more stable release patterns. The bioactivity test reveals that the MZ-xTC scaffolds are capable of developing the formation of HA layers in simulated body fluid (SBF). Next, Staphylococcus aureus and Escherichia coli bacteria were utilized to assess the antimicrobial activity of the MZ-xTC scaffolds. The findings indicate that those scaffolds that incorporate a high level concentration of tetracycline are tougher against bacterial organization than MZ scaffolds. However, the MTT assay demonstrates that the MZ scaffolds containing 1 to 5% tetracycline are more effective to sustain cell viability, whereas MZ-10TC shows some toxicity. The alkaline phosphatase (ALP) activity of the MZ-(1-5)TC was considerably higher than that of MZ-10TC on the 3 and 7 days, implying higher osteoblastic differentiation. All the findings suggest that the MZ-xTC scaffolds containing 1 to 5% tetracycline is a promising candidate for bone tissue healing due to excellent antibacterial activity and biocompatibility.
  6. Bakhsheshi-Rad HR, Hamzah E, Ying WS, Razzaghi M, Sharif S, Ismail AF, et al.
    Materials (Basel), 2021 Apr 12;14(8).
    PMID: 33921460 DOI: 10.3390/ma14081930
    Magnesium has been recognized as a groundbreaking biodegradable biomaterial for implant applications, but its use is limited because it degrades too quickly in physiological solutions. This paper describes the research on the influence of polycaprolactone (PCL)/chitosan (CS)/zinc oxide (ZnO) composite coating (PCL/CS/ZnO) on the corrosion resistance and antibacterial activity of magnesium. The PCL/CS film presented a porous structure with thickness of about 40-50 μm, while after incorporation of ZnO into the PCL/CS, a homogenous film without pores and defects was attained. The ZnO embedded in PCL/CS enhanced corrosion resistance by preventing corrosive ions diffusion in the magnesium substrate. The corrosion, antibacterial, and cell interaction mechanism of the PCL/CS/ZnO composite coating is discussed in this study. In vitro cell culture revealed that the PCL/CS coating with low loaded ZnO significantly improved cytocompatibility, but coatings with high loaded ZnO were able to induce some cytotoxicity osteoblastic cells. It was also found that enhanced antibacterial activity of the PCL/CS/ZnO coating against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, while less significant antibacterial activity was detected for uncoated Mg and PCL/CS coating. Based on the results, the PCL/CS coatings loaded with low ZnO content may be recommended as a candidate material for biodegradable Mg-based orthopedic implant applications.
  7. Pahlevanzadeh F, Bakhsheshi-Rad HR, Kharaziha M, Kasiri-Asgarani M, Omidi M, Razzaghi M, et al.
    J Mech Behav Biomed Mater, 2021 04;116:104320.
    PMID: 33571842 DOI: 10.1016/j.jmbbm.2021.104320
    Polymethyl methacrylate (PMMA) bone cements (BCs) have some drawbacks, including limited bioactivity and bone formation, as well as inferior mechanical properties, which may result in failure of the BC. To deal with the mentioned issues, novel bioactive polymethyl methacrylate-hardystonite (PMMA-HT) bone cement (BC) reinforced with 0.25 and 0.5 wt% of carbon nanotube (CNT) and reduced graphene oxide (rGO) was synthesized. In this context, the obtained bone cements were evaluated in terms of their mechanical and biological characteristics. The rGO reinforced bone cement exhibited better mechanical properties to the extent that the addition of 0.5 wt% of rGO where its compressive and tensile strength of bioactive PMMA-HT/rGO cement escalated from 92.07 ± 0.72 MPa, and 40.02 ± 0.71 MPa to 187.48 ± 5.79 MPa and 64.92 ± 0.75 MPa, respectively. Besides, the mechanisms of toughening, apatite formation, and cell interaction in CNT and rGO encapsulated PMMA have been studied. Results showed that the existence of CNT and rGO in BCs led to increase of MG63 osteoblast viability, and proliferation. However, rGO reinforced bone cement was more successful in supporting MG63 cell attachment compared to the CNT counterpart due to its wrinkled surface, which made a suitable substrate for cell adhesion. Based on the results, PMMA-HT/rGO can be a proper bone cement for the fixation of load-bearing implants.
  8. Saud SN, Hosseinian S R, Bakhsheshi-Rad HR, Yaghoubidoust F, Iqbal N, Hamzah E, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Nov 01;68:687-694.
    PMID: 27524069 DOI: 10.1016/j.msec.2016.06.048
    In the present work, the microstructure, corrosion, and bioactivity of graphene oxide (GO) coating on the laser-modified and -unmodified surfaces of TiNb shape memory alloys (SMAs) were investigated. The surface morphology and chemical composition was examined using field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD). The surface modification was carried out via a femtosecond laser with the aim to increase the surface roughness, and thus increase the adhesion property. FE-SEM analysis of the laser-treated Ti-30at.% Nb revealed the increase in surface roughness and oxygen/nitrogen containing groups on the Ti-30at.% Nb surface after being surface modified via a femtosecond laser. Furthermore, the thickness of GO was increased from 35μm to 45μm after the surface was modified. Potentiodynamic polarisation and electrochemical impedance spectroscopy studies revealed that both the GO and laser/GO-coated samples exhibited higher corrosion resistance than that of the uncoated TiNb SMA sample. However, the laser/GO-coated sample presented the highest corrosion resistance in SBF at 37°C. In addition, during soaking in the simulated body fluid (SBF), both the GO and laser/GO coating improved the formation of apatite layer. Based on the bioactivity results, the GO coating exhibited a remarkable antibacterial activity against gram-negative bacteria compared with the uncoated. In conclusion, the present results indicate that Ti-30at.% Nb SMAs may be promising alternatives to NiTi for certain biomedical applications.
  9. Bakhsheshi-Rad HR, Hamzah E, Low HT, Kasiri-Asgarani M, Farahany S, Akbari E, et al.
    Mater Sci Eng C Mater Biol Appl, 2017 Apr 01;73:215-219.
    PMID: 28183601 DOI: 10.1016/j.msec.2016.11.138
    In this work, binary Zn-0.5Al and ternary Zn-0.5Al-xMg alloys with various Mg contents were investigated as biodegradable materials for implant applications. Compared with Zn-0.5Al (single phase), Zn-0.5Al-xMg alloys consisted of the α-Zn and Mg2(Zn, Al)11 with a fine lamellar structure. The results also revealed that ternary Zn-Al-Mg alloys presented higher micro-hardness value, tensile strength and corrosion resistance compared to the binary Zn-Al alloy. In addition, the tensile strength and corrosion resistance increased with increasing the Mg content in ternary alloys. The immersion tests also indicated that the corrosion rates in the following order Zn-0.5Al-0.5Mg
  10. Bakhsheshi-Rad HR, Ismail AF, Aziz M, Akbari M, Hadisi Z, Omidi M, et al.
    Int J Biol Macromol, 2020 Apr 15;149:513-521.
    PMID: 31954780 DOI: 10.1016/j.ijbiomac.2020.01.139
    Skin and soft tissue infections are major concerns with respect to wound repair. Recently, anti-bacterial wound dressings have been emerging as promising candidates to reduce infection, thus accelerating the wound healing process. This paper presents our work to develop and characterize poly(vinyl alcohol) (PVA)/chitosan (CS)/silk sericin (SS)/tetracycline (TCN) porous nanofibers, with diameters varying from 305 to 425 nm, both in vitro and in vivo for potential applications as wound dressings. The fabricated nanofibers possess a considerable capacity to take up water through swelling (~325-650%). Sericin addition leads to increased hydrophilicity and elongation at break while decreasing fiber diameter and mechanical strength. Moreover, fibroblasts (L929) cultured on the nanofibers with low sericin content (PVA/CS/1-2SS) displayed greater proliferation compared to those on nanofibers without sericin (PVA/CS). Nanofibers loaded with high sericin and tetracycline content significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. In vivo examination revealed that PVA/CS/2SS-TCN nanofibers enhance wound healing, re-epithelialization, and collagen deposition compared to traditional gauze and nanofibers without sericin. The results of this study demonstrate that the PVA/CS/2SS-TCN nanofiber creates a promising alternative to traditional wound dressing materials.
  11. Bakhsheshi-Rad HR, Ismail AF, Aziz M, Akbari M, Hadisi Z, Khoshnava SM, et al.
    Mater Sci Eng C Mater Biol Appl, 2020 Jun;111:110812.
    PMID: 32279830 DOI: 10.1016/j.msec.2020.110812
    Magnesium (Mg) alloys present great potential for the development of orthopedic implants, whereas, their high degradation rate and poor antibacterial performance have restricted orthopedic applications. In this work, PLLA/GO-AgNP (poly-L-lactic acid/graphene oxide- silver nanoparticle) with different concentration of GO-AgNPs were deposited on Mg alloy via electrospinning method for enhancement of corrosion resistance and antibacterial performance. The result revealed that incorporation of GO into PLLA fibrous considerably slowed down the degradation rate of Mg alloy substrate and reduced the H2 release rate from the substrate. Also, co-incorporation of GO and AgNPs into PLLA fibrous resulted in substantial escalate in compressive strength after immersion in simulated body fluid (SBF). Antibacterial activity test exhibited that Mg alloy and neat PLLA fibrous presented minimal inhibition area toward Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In contrast, using PLLA/GO-AgNPs fibrous improved antibacterial performance against both bacteria. Cytocompatibility results indicated that PLLA/GO-AgNPs fibrous with a low amount of GO-AgNPs enhanced cell proliferation and growth while high co-incorporation of GO-AgNPs showed a negative effect on cell proliferation. Taken together, PLLA/1GO-AgNPs fibrous coating shows suitable corrosion resistance, cytocompatibility, and antibacterial function for use in orthopedic applications.
  12. Parham S, Kharazi AZ, Bakhsheshi-Rad HR, Ghayour H, Ismail AF, Nur H, et al.
    Materials (Basel), 2020 May 06;13(9).
    PMID: 32384813 DOI: 10.3390/ma13092153
    Pharmaceutical nano-fibers have attracted widespread attention from researchers for reasons such as adaptability of the electro-spinning process and ease of production. As a flexible method for fabricating nano-fibers, electro-spinning is extensively used. An electro-spinning unit is composed of a pump or syringe, a high voltage current supplier, a metal plate collector and a spinneret. Optimization of the attained nano-fibers is undertaken through manipulation of the variables of the process and formulation, including concentration, viscosity, molecular mass, and physical phenomenon, as well as the environmental parameters including temperature and humidity. The nano-fibers achieved by electro-spinning can be utilized for drug loading. The mixing of two or more medicines can be performed via electro-spinning. Facilitation or inhibition of the burst release of a drug can be achieved by the use of the electro-spinning approach. This potential is anticipated to facilitate progression in applications of drug release modification and tissue engineering (TE). The present review aims to focus on electro-spinning, optimization parameters, pharmacological applications, biological characteristics, and in vivo analyses of the electro-spun nano-fibers. Furthermore, current developments and upcoming investigation directions are outlined for the advancement of electro-spun nano-fibers for TE. Moreover, the possible applications, complications and future developments of these nano-fibers are summarized in detail.
  13. Parham S, Kharazi AZ, Bakhsheshi-Rad HR, Nur H, Ismail AF, Sharif S, et al.
    Antioxidants (Basel), 2020 Dec 21;9(12).
    PMID: 33371338 DOI: 10.3390/antiox9121309
    Recently, increasing public concern about hygiene has been driving many studies to investigate antimicrobial and antiviral agents. However, the use of any antimicrobial agents must be limited due to their possible toxic or harmful effects. In recent years, due to previous antibiotics' lesser side effects, the use of herbal materials instead of synthetic or chemical drugs is increasing. Herbal materials are found in medicines. Herbs can be used in the form of plant extracts or as their active components. Furthermore, most of the world's populations used herbal materials due to their strong antimicrobial properties and primary healthcare benefits. For example, herbs are an excellent material to replace nanosilver as an antibiotic and antiviral agent. The use of nanosilver involves an ROS-mediated mechanism that might lead to oxidative stress-related cancer, cytotoxicity, and heart diseases. Oxidative stress further leads to increased ROS production and also delays the cellular processes involved in wound healing. Therefore, existing antibiotic drugs can be replaced with biomaterials such as herbal medicine with high antimicrobial, antiviral, and antioxidant activity. This review paper highlights the antibacterial, antiviral, and radical scavenger (antioxidant) properties of herbal materials. Antimicrobial activity, radical scavenger ability, the potential for antimicrobial, antiviral, and anticancer agents, and efficacy in eliminating bacteria and viruses and scavenging free radicals in herbal materials are discussed in this review. The presented herbal antimicrobial agents in this review include clove, portulaca, tribulus, eryngium, cinnamon, turmeric, ginger, thyme, pennyroyal, mint, fennel, chamomile, burdock, eucalyptus, primrose, lemon balm, mallow, and garlic, which are all summarized.
  14. Nazemi N, Rajabi N, Aslani Z, Kharaziha M, Kasiri-Asgarani M, Bakhsheshi-Rad HR, et al.
    J Biomater Appl, 2023 Jan;37(6):979-991.
    PMID: 36454961 DOI: 10.1177/08853282221140672
    Porous structure, biocompatibility and biodegradability, large surface area, and drug-loading ability are some remarkable properties of zeolite structure, making it a great possible option for bone tissue engineering. Herein, we evaluated the potential application of the ZSM-5 scaffold encapsulated GEN with high porosity structure and significant antibacterial properties. The space holder process has been employed as a new fabrication method with interconnected pores and suitable mechanical properties. In this study, for the first time, ZSM-5 scaffolds with GEN drug-loading were fabricated with the space holder method. The results showed excellent open porosity in the range of 70-78% for different GEN concentrations and appropriate mechanical properties. Apatite formation on the scaffold surface was determined with Simulation body fluid (SBF), and a new bone-like apatite layer shaping on all samples confirmed the in vitro bioactivity of ZSM-5-GEN scaffolds. Also, antibacterial properties were investigated against both gram-positive and gram-negative bacteria. The incorporation of various amounts of GEN increased the inhibition zone from 24 to 28 (for E. coli) and 26 to 37 (for S. aureus). In the culture with MG63 cells, great cell viability and high cell proliferation after 7 days of culture were determined.
  15. Amirzade-Iranaq MT, Omidi M, Bakhsheshi-Rad HR, Saberi A, Abazari S, Teymouri N, et al.
    Materials (Basel), 2023 Feb 25;16(5).
    PMID: 36903033 DOI: 10.3390/ma16051919
    This study attempts to synthesize MgZn/TiO2-MWCNTs composites with varying TiO2-MWCNT concentrations using mechanical alloying and a semi-powder metallurgy process coupled with spark plasma sintering. It also aims to investigate the mechanical, corrosion, and antibacterial properties of these composites. When compared to the MgZn composite, the microhardness and compressive strength of the MgZn/TiO2-MWCNTs composites were enhanced to 79 HV and 269 MPa, respectively. The results of cell culture and viability experiments revealed that incorporating TiO2-MWCNTs increased osteoblast proliferation and attachment and enhanced the biocompatibility of the TiO2-MWCNTs nanocomposite. It was observed that the corrosion resistance of the Mg-based composite was improved and the corrosion rate was reduced to about 2.1 mm/y with the addition of 10 wt% TiO2-1 wt% MWCNTs. In vitro testing for up to 14 days revealed a reduced degradation rate following the incorporation of TiO2-MWCNTs reinforcement into a MgZn matrix alloy. Antibacterial evaluations revealed that the composite had antibacterial activity, with an inhibition zone of 3.7 mm against Staphylococcus aureus. The MgZn/TiO2-MWCNTs composite structure has great potential for use in orthopedic fracture fixation devices.
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