Nanotechnology and Advanced Materials

Polymer scaffolds have many different functions in the field of tissue engineering. They are applied as space filling agents, as delivery vehicles for bioactive molecules, and as three-dimensional structures that organize cells and present stimuli to direct the formation of a desired tissue. Much of the success of scaffolds in these roles hinges on finding an appropriate material to address the critical physical, mass transport, and biological design variables inherent to each application. Hydrogels are an appealing scaffold material because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. Consequently, hydrogels have been utilized as scaffold materials for drug and growth factor delivery, engineering tissue replacements, and a variety of other applications.

Calcium phosphate cements (CPCs) are highly promising for clinical uses due to their in situ-setting ability, excellent osteoconductivity and bone-replacement capability. However, the low strength limits their uses to non-load-bearing applications. In the present research, first, bioactive glass fibers (BGFs) in the ternary SiO2-CaO-P2O5 system were prepared, and then the fiber composites with compositions based on CPC and BGFs were prepared and characterized. Then, the effect of structure and amount of BGF incorporation into the CPC system, and the effect of mechanical compaction on the fiber-modified system were investigated. The results showed that the compressive strength of the set cements without any BGFs was 0.635 MPa which was optimally increased to 3.69 MPa by applying 15% BGF and then decreased by further addition of it. In addition, both the work-of-fracture and elastic modulus of the cement were considerably increased after applying the fibers in the cement composition. Also, the setting time slightly decreased by applying the fibers. In summary, processing parameters were tailored to achieve optimum mechanical properties and strength. The prepared composite may be useful in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques.

In this article 5-25 V% of a sol-gel bioglass fiber was incorporated into calcium phosphate bone cement to improve its mechanical properties. Compressive strength, work of fracture, elastic modulus and setting time of the cement were investigated as well as phase changes occurring during soaking the specimens in simulated body fluid (SBF). The cement microstructure was also observed by scanning electron microscope (SEM). The results showed that the compressive strength of the set cements without any fibers was 0.635 MPa which was optimally increased to 3.69 MPa by using 15% fibers and then decreased by further addition of the glass phase. In addition, both the work-of-fracture and elastic modulus of the cement were considerably increased when using the fibers in the cement composition. Setting time slightly decreased by using the fibers.
A considerable content of the reactants in both fiber-free and fiber-containing cements were transformed to the apatite phase
during soaking sample in SBF.
http://jcpr.kbs-lab.co.kr/english/jcpr_journal_2010_3.htm

ricated from cross-linked gelatine (Gel) and nano bioactive glass (nBG) through layer solvent casting combined
with freeze-drying and lamination techniques. This study has developed a new composition to produce a new bioactive nanocomposite which is porous with interconnected microstructure, pore sizes are 200-500 μm, porosity are 72%-86%. Also, we have reported formation of chemical bonds between nBG and Gel for the first time. Finally, the in vitro cytocompatability of the scaffolds was assessed using MTT assay and cell attachment study. Results indicated no sign of toxicity and cells found to be attached to the pore walls offered by the scaffolds.
These results suggested that the developed nanocomposite scaffold possess the prerequisites for bone tissue engineering scaffolds and it can be used for tissue engineering applications.

In this study, macroporous bioactive nanocomposite scaffolds were developed using cross-linked gelatin and bioactive glass (BaG) nanoparticles. First, BaG nanoparticles were synthesized via sol–gel method and characterized. Then, macroporous nanocomposites were prepared through layer solvent casting combined with freeze-drying and lamination techniques. This research has developed a new composition to produce a new bioactive nanocomposite which is porous with three-dimensional (3D) inter-connected microstructure, pore sizes are 200–500 μm, porosity are 72–86% and BaG nanoparticles are dispersed evenly among cross-linked gelatin matrices. It is mentionable that in this study, we have reported the formation of chemical bonds between BaG nanoparticles and gelatin for the first time. Finally, the in vitro cytocompatibility of the nanocomposite scaffolds was tested using SaOS-2 cell line.

In the present study, release properties of antibiotic-loaded cement-type nanocomposites of biomimetic apatite and calcium sulfate were studied. Nanocrystalline component of the nanocomposite was synthesized by soaking a mixture of calcium phosphate reactants in tris-buffered simulated body fluid (SBF). The release patterns of cephalexin and
gentamicin from both pure calcium sulfate and nanocomposite cements into SBF were collected up to 144 h and fitted by Higuchi and Weibull equations. The effect of loaded
antibiotics on physical properties of the cements was also evaluated. Fast release behavior of both antibiotics was obtained from calcium sulfate matrix, in which 80–85% of the loaded antibiotics were liberated during the first 10 h of elution. In contrast, an administered elution was acquired from nanonocomposite materials so that the release was controlled, in all cases, by a combined mechanism; major mechanism was drug diffusion through the matrix and the
minor was matrix dissolution. The results showed that the initial setting time and injectability of cements were increased from 7 min and 71% for pure calcium sulfate cement (powder-to liquid ratio 5 2.5 g/mL) to 33 min and 95% for the nanocomposite cement containing 60 wt % apatite, respectively. The compressive strength of nanocomposite was about 0.9 MPa, nearly four times lower than that of pure calcium sulfate. In addition, the use of cephalexin
monohydrate did not influence the setting time and compressive strength of the cements, whereas (adding) gentamicin sulfate significantly improved these properties.

In this study, nanocomposite of 50 wt% calcium sulfate and 50 wt% nanocrystalline apatite was produced and its biocompatibility, physical and structural properties were compared with pure calcium sulfate (CS) cement. Indomethacin (IM), a non-steroidal anti-inflammatory drug, was also loaded on both CS and nanocomposite cements and its in vitro release was evaluated over a period of time. The effect of the loaded IM on basic properties of the cements was also investigated. Biocompatibility tests showed a partial cytotoxicity in CS cement due to the reduced number of viable mouse fibroblast L929 cells in contact with the samples as well as spherical morphologies of the cells. However, no cytotoxic effect was observed for nanocomposite cement and no significant difference was found between the number
of the cells seeded in contact with this specimens and culture plate as control. Other results showed that the setting time and injectability of the nanocomposite cement was much higher than those of CS cement, whereas reverse result obtained for compressive strength. In addition, incorporation of IM into compositions slightly increased the initial setting time and injectability of the cements and did not change
their compressive strength. While a fast IM release was observed from CS cement in which about 97% of
the loaded drug was released during 48 h, nanocomposite cement showed a sustained release behavior in
which 80% of the loaded IM was liberated after 144 h. Thus, the nanocomposite can be a more appropriate
carrier than CS for controlled release of IM in bone defect treatments.

In this study, the compressive strength and bioactivity of strong polymeric calcium phosphate cement (PCPC), made by mixing a calcium phosphate powder (a mixture of tetracalcium phosphate and dicalcium phosphate dihydrate) and an aqueous solution of poly(acrylic/itaconic)
acid, were investigated. The characteristics of the cement such as phase composition, setting reaction products and microstructure were analysed and compared to those of a control sample made by the same solid phase and water as a liquid. The hard tissue healing capability of PCPC was tested in a rabbit model by radiographical observations of the healing process as well as the cement condition. The results showed that the compressive strength of the set PCPC was about 35 MPa before soaking in a simulated body fluid (SBF), which was much higher than that of the control specimen. However, it sharply decreased when the cement was immersed in the SBF. X-ray diffraction analysis revealed that tricalcium phosphate was formed in the set PCPC and only a small amount of hydroxyapatite was produced after seven days soaking. In contrast, hydroxyapatite was almost the only phase of the control specimen after the soaking period.
Radiography tests showed a cement (PCPC) with an irregular macrostructure after three months implantation, with a decreased radiopacity, and without any periosteal or intercortical callus formation.

bisphosphonates are a class of drugs that inhibit osteoclast action and the resoption of bone.
Osteoporosis is caused to abnormal function of osteoclasts. When calcium phosphate cements in
osteoprotics patients are used, loosening will be happened because of increased activity of
osteoclast in implant situation. If we use bisphosphonates in calcium phosphate cement
composition this problem will overcome. In addition as we have investigated the properties of
biphosphonate added cement, we observed better properties that only made by some additives, so
bisphosphonate could be a very interesting additive too, for achieving to optimum properties.

Human beings are often infected by microorganisms in the living environment. Among various natural and inorganic substances, silver or silver ions have a powerful antibacterial activity. In the present study, the bioactivity and antibacterial activity of the SiO2–CaO–P2O5–Ag2O was compared with that of its ternary counterpart glass system (as a control sample) in vitro. The molar ratio of silver oxide in the bioactive glass composition was considered as different amount (0.5%, 1% and 2%). The surface characterization was evaluated after soaking in simulated body fluid (SBF). The sharpest apatite peak in X-ray diffraction (XRD) analyse after 7 days soaking in SBF was observed for 2% Ag sample (2%Ag-BG). Hence, the antibacterial effects of 2%Ag-BG sample against 2 gram negatives bacterium were examined by agar plate test. The result showed that the amount of silver did not prevent the HAp formation. Also, the antibacterial properties of 2%Ag-BG sample indicated near 100% bactericidal ratio (according to the width of antibacterial halo).

Basic drawbacks of calcium phosphate cements (CPCs) are the brittleness and low strength behavior which prohibit their use in many stress-bearing locations, unsupported defects, or reconstruction of thin bones. Recently, to solve these problems, researchers investigated the incorporation of fibers into CPCs to improve their strength. In the present study, various amounts of a highly bioactive glass fiber were incorporated into calcium phosphate bone cement. The obtained results showed that the compressive strength of the set cements without any fibers optimally increased by further addition of the fiber phase. Also, both the work-of-fracture and elastic modulus of the cement were considerably increased after applying the fibers in the cement composition. Herein, with the aim of using the reinforced-CPC as appropriate bone filler, the prepared sample was evaluated in vitro using simulated body fluid (SBF) and osteoblast cells. The samples showed significant enhancement in bioactivity within few days of immersion in SBF solution. Also, in vitro experiments with osteoblast cells indicated an appropriate penetration of the cells, and also the continuous increase in cell aggregation on the samples during the incubation time demonstrated the ability of the reinforced-CPC to support cell growth. Therefore, we concluded that this filler and strong reinforced-CPC may be beneficial to be used as bone fillers in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques.

Key Engineering Materials Vols. 493-494 (2012) pp 209-214.

Ag‏ ions are known for their antibacterial effects. Ag containing silicate glasses have been extended to create bioactive glasses exhibiting inhibitory effects on bacterial growth using different techniques. In this work, calcium and calcium/silver silicophosphate glasses were synthesized from the sol–gel process and their physico-chemical and in vitro biological properties were studied and compared to each other. The effect of silver concentration on in vitro bioactivity and antibacterial properties of the glasses was investigated. Ag2O was substituted for CaO in the glass formula up to 2 mol% and in vitro bioactivity of the samples was evaluated by soaking them in simulated body fluid followed by structural characterization using XRD, FTIR and SEM techniques. The results showed that both glasses favored precipitation of calcium phosphate layer when they were soaked in simulated body fluid; however the morphology of apatite crystals changed for 2%mol silver containing sample. 2% mol Ag2O substituted for CaO seemed to stimulate the rate of precipitation slightly. The in vitro biodegradation rate of the silver/calcium silicophosphate glasses was lower than that of silver-free one (control). Also, the antibacterial properties of the samples indicated that these effects improved by increasing silver concentration in bioactive glass composition.

Calcium phosphate cements (CPCs) have been used in a number of medical and dental procedures due to their excellent osteoconductivity and bone replacement capability. However, the low mechanical properties of CPCs prohibit their usage in many unsupported defects and stress bearing locations. Bioactive glass fiber (BGF) reinforced-CPC with enhanced mechanical property has been recently developed [Nezafati et al. 2011, Ceramics International]. In the present study, the in vitro bioactivity and cellular properties of the CPC optimally reinforced with 15 vol% BGFs were evaluated and compared with a control group, i.e. unreinforced CPC. The samples were soaked in simulated body fluid (SBF) for different time intervals and were then characterized by various techniques. Carbonate substituted apatite crystals with oriented plate-like morphology were also found on the surface of the samples. Furthermore, rat-derived osteoblastic cells were seeded on the samples for different times and evaluated in terms of proliferation, morphology and alkaline phosphatase (ALP) activity. In addition, the proliferation of osteoblastic cells on samples and increasing in level of alkaline phosphatase enzyme were observed as a function of time. The obtained results indicated that the reinforced composite made of CPC and BGFs could be considered as a highly bioactive material for bone tissue defect treatment after successful passage of in vivo experiments.

In the present study, a bioceramic-based composite was prepared by sintering compacts made up of mixtures of hydroxyapatite (HA) and sol–gel-derived bioactive glass (64SiO2-26CaO-5MgO-5ZnO) (based on mol%) powders. HA powder was mixed with different concentrations of the glass powders up to 30 wt.%. The effect of adding bioactive glass powder to HA matrix, on the mechanical properties of the composite was assessed by compression test. The specimen with the highest compressive strength was chosen to be immersed in simulated body fluid (SBF) to study apatite forming ability and dissolution behavior. It was found that compressive strength of the specimen was decreased 65% after maintaining in the SBF for 14 days. X-ray diffraction (XRD) showed prevalence of HA and β-TCP related peaks. Also, the surface morphology of the composite was observed using scanning electron microscopy (SEM). The study of degradation behavior revealed Si release capability of this composite. Biological evaluations in vitro confirmed the composite studied could induce osteoblast-like cells' activities.

Dycal® is a paste-paste calcium hydroxide dental cement uses as pulp capping and liner in dentistry. First paste (base paste) contains titanium dioxide and barium sulphate in glycol disalicylate and second paste (catalyst paste) contains calcium hydroxide, zinc oxide and zinc stearate in ethyl toluene sulphonamide. Equal amounts of base and catalyst paste were mixed together and a hard mass is obtained after a certain time. The set material consists of TiO2, ZnO (fillers), BaSO4 (radiopacifier) and free unreacted Ca(OH)2 dispersed in an amorphous calcium phenolate matrix. This unreacted calcium hydroxide is responsible for biological properties of Dycal® (antibacterial and formation of reparative dentin).
In this research Dycal® has been fabricated and furthermore glycol disalicylate was gradually replaced by methyl salicylate up to 20 % in base paste. Cements were characterized by X-ray diffraction (XRD) and Fourier
transform infra-red (FTIR) and scanning electron microscopy (SEM). Also effect of the replacement was investigated on setting time, water solubility, pH and compressive strength of the cement. Results showed that unreacted calcium hydroxide decreased in set cement when methyl salicylate increase in base paste and therefore, and pH of distilled water containing cement decrease by this replacement. Setting time and water solubility also decreased when methyl salicylate increased in base paste (from 5.5 to 3 min and 4.5% to 2.5% respectively). The compressive strength showed no changes by this replacement.

In the present study, a bioceramic-based composite with remarkable mechanical properties and in vitro apatite forming ability was synthesized by sintering compacts made up of mixtures of hydroxyapatite (HA) and sol-gel derived bioactive glass (64SiO2-26CaO-5MgO-5ZnO) (based on mole %). HA was synthesized through co-precipitation method. The stabilization temperature of the bioactive glass was set to be 700 ºC according to simultaneous thermal analysis (STA). Laser Particle Size Analysis (LPSA) was used to compare the particle size distributions of the synthetic powders. HA matrix was mixed with different weight percentages of bioactive glass (5, 10, 15, 20, 25 and 30 wt. %) and compressed by 80 MPa pressure. After sintering the uniaxial compression test of the samples was done and the specimen with the highest compressive strength (20 wt. % bioactive glass) was selected to be immersed in the Simulated Body Fluid (SBF) for 3, 7 and 14 days. The results showed that the compressive strength of the sample decreased after maintaining in the SBF. Also, inductively coupled plasma analysis (ICP) was used to study the ion release behavior of the sample in the SBF. Finally, phase composition, microstructure and functional groups in composite were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) techniques, respectively.

Calcium phosphate cements (CPCs) have been used in a number of medical and dental procedures due to their excellent osteoconductivity and bone replacement capability. However, the low mechanical properties of CPCs prohibit their usage in many unsupported defects and stress bearing locations. Bioactive glass fiber (BGF) reinforced-CPC with enhanced mechanical property has been recently developed [Nezafati et al. 2011, Ceramics International]. In the present study, the in vitro bioactivity and cellular properties of the CPC optimally reinforced with 15 vol% BGFs were evaluated and compared with a control group, i.e. unreinforced CPC. The samples were soaked in simulated body fluid (SBF) for different time intervals and were then characterized by various techniques. Carbonate substituted apatite crystals with oriented plate-like morphology were also found on the surface of the samples. Furthermore, rat-derived osteoblastic cells were seeded on the samples for different times and evaluated in terms of proliferation, morphology and alkaline phosphatase (ALP) activity. In addition, the proliferation of osteoblastic cells on samples and increasing in level of alkaline phosphatase enzyme were observed as a function of time. The obtained results indicated that the reinforced composite made of CPC and BGFs could be considered as a highly bioactive material for bone tissue defect treatment after successful passage of in vivo experiments.

In this research, sol–gel-derived nanostructured calcium magnesium silicate (merwinite)-based scaffolds were fabricated by water-based freeze casting method. The effect of cooling rate and sintering temperature on pore sizes and mechanical characteristics of the scaffolds was studied. Microstructure and surface morphology of scaffolds were also observed by scanning electron microscopy before and after various time intervals of soaking in simulated body fluid. The results showed that increasing temperature at the constant rate led to increasing the parameters of volume and linear shrinkage, strength (σ), and Young’s modulus (E) but decreasing porosity. This increase was significant for strength and Young’s modulus. In addition, with the increase of rate at the constant temperature, the parameters of volume and linear shrinkage and also porosity decreased whereas strength and Young’s modulus increased significantly. According to the obtained mechanical results, the best mechanical properties were achieved when the scaffold was prepared at cooling rate and sintering temperature of 277.15°K/min and 1623.15°K, respectively (E = 0.048 GPa and σ = 2 MPa). These values were closer to the lower limit of the values for cancellous bone. The acellular in vitro bioactivity revealed that different apatite morphologies were formed on the surfaces for various periods of soaking time when the scaffolds prepared at the freezing temperature of 277.15°K/min and at the two different sintering temperatures. The favorable mechanical behavior of the porous constructs, coupled with the ability of forming apatite particles on the surface of scaffold, indicates the potential of the present freeze casting route for the production of porous scaffolds for bone tissue engineering.

In  the  present  research,  strontium  containing  nano-bioactive  glass  (NBG-Sr)  was
synthesized by sol-gel method. The morphology was analyzed by transmission electron microscope
(TEM).  Different  amounts  (0.5  to  5  wt%)  of  NBG-Sr  were  then  added  to  biphasic  calcium
phosphate  (BCP).  They  were  sintered  at  different  temperatures,  i.e.,  1100,  1200  and  1300  °C  and
changes in physical and mechanical properties were investigated. A sharp decrease in pore volume
was  observed  as  the  temperature  increased.  The  maximum  bending  strength  (~45  MPa)  was
achieved for BCP which was mixed with 3 wt% NBG-Sr and sintered at 1200 °C. This value was
approximately  the  same  when  it  was  sintered  at  1300  °C.  The  bending  strength  failed  when  both
lower  and  higher  amounts  of  3  wt%  NBG-Sr  were  utilized.  Therefore,  sintering  of  composites  at
1200  °C  was  economically  reasonable.  The  X-ray  results  showed  that  NBG-Sr  additive  did  not
change  the  phase  composition  of  BCP  when  it  was  heat  treated  at  1200  °C.  The  attachment  and
proliferation  of  rat  calvarium-derived  osteoblasts  on  samples  sintered  at  1200  °C  were  also
evaluated by scanning electron microscopy (SEM). Based on cell studies, all NBG-Sr-added BCPs
supported  attachment  and  proliferation  of  osteoblastic  cells.  Overall,  biphasic  calcium  phosphate
materials  with  improved  mechanical  and  biological  properties  can  be  produced  by  using  certain
quantity of strontium-containing bioactive glass particles.

The need for bone repair has increased as the population ages. In this research, calcium phosphate cements, with and without chitosan (CS) and hyaluronic acid (HA), were synthesized. The composition and morphological properties of cements were evaluated by X-ray diffraction and scanning electron microscopy. The acellular in vitro bioactivity revealed that different apatite morphologies were formed on the surfaces of cements after soaking in simulated body fluid. The in vitro osteoblastic cell biocompatibility of in situ forming cements was evaluated and compared with those of conventional calcium phosphate cements (CPCs). The viability and growth rate of the cells were similar for all CPCs, but better alkaline phosphatase activity was observed for CPC with CS and HA. Calcium phosphate cements supported attachment of osteoblastic cells on their surfaces. Spindle-shaped osteoblasts with developed cytoplasmic membrane were found on the surfaces of cement samples after 7 days of culture. These results reveal the potential of the CPC–CS/HA composites to be used in bone tissue engineering.