Effects of friction stir processing and nano-hydroxyapatite on the microstructure,hardness,degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications

Nowadays,magnesium alloys are emerging in biomedical implants for their similar properties to natural bones.However,the rapid degradation of magnesium alloys in biological media hinders successful implantation.Refinement of microstructure,as well as reinforcement particles can significantly improve the degradation rate.In this work,multi-pass friction stir processing(FSP)was proposed to synthesize WE43/nano-hydroxyapatite(n HA)surface composite,the microstructure,reinforced particle distribution,micro-hardness,corrosion behavior and in-vitro bioactivity were studied.The subsequent FSP passes of WE43 alloy and WE43/n HA composite refined the grain size which was reduced by 94.29%and 95.92%(2.63 and 1.88μm,respectively)compared to base metal after three passes.This resulted in increasing the microhardness by 120%(90.86 HV0.1)and 135%(105.59 HV0.1)for the WE43 and WE43-n HA,respectively.It is found that increasing FSP passes improved the uniform distribution of n HA particles within the composite matrix which led to improved corrosion resistance and less degradation rate.The corrosion rate of the FSPed WE43/n HA composite after three passes was reduced by 38.2%(4.13 mm/year)and the degradation rate was reduced by 69.7%(2.87 mm/y).This is attributed to secondary phase(Mg24Y5and Mg41Nd5)particle fragmentation and redistribution,as well as a homogeneous distribution of n HA.Additionally,the growing Ca-P and Mg(OH)2layer formed on the surface represented a protective layer that reduced the degradation rate.The wettability test revealed a relatively hydrophilic surface with water contact angle of 49.1±2.2°compared to 71.2±2.1°for base metal.Also,biomineralization test showed that apatite layer grew after immersion 7d in simulated body fluid with atomic ratio of Ca/P 1.60 approaching the stoichiometric ratio(1.67)indicating superior bioactivity of FSPed WE43/n HA composite after three passes.These results raise that the grain refinement by FSP and introduction of n HA particles significantly improved the degradation rate and in-vitro bioactivity of WE43 alloy for biomedical applications.

Review on the Fabrication of Surface Functional Structures for Enhancing Bioactivity of Titanium and Titanium Alloy Implants

Titanium and its alloys have been widely applied in many biomedical fields because of its excellent mechanical properties,corrosion resistance and good biocompatibility.However,problems such as rejection,shedding and infection will occur after titanium alloy implantation due to the low biological activity of titanium alloy surface.The structures with specific functions,which can enhance osseointegration and antibacterial properties,are fabricated on the surface of titanium implants to improve the biological activity between the titanium implants and human tissues.This paper presents a comprehensive review of recent developments and applications of surface functional structure in titanium and titanium alloy implants.The applications of surface functional structure on different titanium and titanium alloy implants are introduced,and their manufacturing technologies are summarized and compared.Furthermore,the fabrication of various surface functional structures used for titanium and titanium alloy implants is reviewed and analyzed in detail.Finally,the challenges affecting the development of surface functional structures applied in titanium and titanium alloy implants are outlined,and recommendations for future research are presented.

Investigation of bioactivity and biodegradability of Mg-bioceramic implants:An in vitro study for biomedical applications

In this study,Mg-based composites,by the addition of ZnO,Ca_(2)ZnSi_(2)O_(7),Ca_(2)MgSi_(2)O_(7),and CaSiO_(3)as bioactive agents,were fabricated using friction stir processing.The microstructure and in vitro assessment of bioactivity,biodegradation rate,and corrosion behavior of the resultant composites were investigated in simulated body fluid(SBF).The results showed that during the immersion of composites in SBF for 28 d,due to the release of Ca^(2+)and PO_(4)^(3-)ions,hydroxyapatite(HA)crystals with cauliflower shaped morphology were deposited on the surface of composites,confirming good bioactivity of composites.In addition,due to the uniform distribution of bioceramic powders throughout Mg matrix,grain refinement of the Mg matrix,and uniform redistribution of secondary phase particles,the polarization resistance increased,and the biodegradation rate of composites significantly reduced compared to monolithic Mg matrix.The polarization corrosion resistance of Mg-ZnO increased from 0.216 to 2.499 kΩ/cm^(2)compared to monolithic Mg alloy.Additionally,Mg-ZnO composite with the weight loss of 0.0217 g after 28 d immersion showed lower weight loss compared to other samples with increasing immersion time.Moreover,Mg-ZnO composite with the biodegradation rate of 37.71 mm/a exhibited lower biodegradation rate compared to other samples with increasing immersion time.

Effect of Ta_(2)O_(5)nanoparticles on bioactivity,composition,structure,in vitro and in vivo behavior of PEO coatings on Mg-alloy

The present study investigates the physical and chemical characteristics,behavior in vitro and in vivo,and biocompatibility of coatings containing Ta_(2)O_(5),which are obtained by plasma electrolytic oxidation(PEO)on MA8 magnesium alloy.The obtained coatings demonstrate in vivo biocompatibility and in vitro bioactivity.Compared to the base PEO coating,the layers containing Ta_(2)O_(5)facilitate the development of apatite in simulated body fluid,suggesting that the inclusion of nanoparticles improves bioactivity of the coatings.It was found that incorporation of Ta_(2)O_(5)nanoparticles increases roughness and porosity of the formed layers by increasing particle concentration in electrolytes for the PEO process contributing to sufficient soft tissue ingrowth in vivo.Based on in vivo studies,these coatings also provide favorable tissue response and minimal inflammatory reaction in comparison with the bare magnesium alloy due to protection of living tissues from deleterious corrosion events of magnesium implant such as local alkalization and intense hydrogen evolution.The results obtained in the present study concluded biocompatibility,tissue integration of the PEO coatings containing Ta_(2)O_(5)nanoparticles making them a promising protective layer for biodegradable magnesium implants.

Preparation of micro-nanostructure on titanium implants and its bioactivity

Surface modification of medical implants was considered as an effective method to improve the cellular behaviors and the integration of tissue onto materials. The micro-nanostructured surface on the titanium alloy was prepared by laser treatment and multiple acid etching. The surface morphologies of different titanium alloy substrates were characterized by scanning electron microscopy (SEM). The effects of micro-nanostructured surfaces on the cellular responses were investigated in vitro by observing hydroxyapatite formation, cell morphology and cell adhesion. The results indicate that the micro-sized structure promoted the adhesion and proliferation of cultured osteoblasts. Furthermore, the micro-nanostructured surface was more conducive to cell adhension stretching compared with the micro-structured surface. All results suggest that the micro-nanostructured surface improved the biocompatibility and integration of tissue onto titanium alloy implants.

Anti-insect Bioactivity of the Extracts from Cichorium intybus L. Leaves

In order to develop a new plant-source insecticide,some active components from Cichorium intybus L.were extracted with mineral ether,ethyl ether,ethyl acetate,respectively.It were testified the effects of the components on the development of Mythimna separate Walker and anti-feeding by feeding and weighting method.The results showed that the body weight of the larvae fed by the extracts with organic solvents was significantly lower than the control;the body weight of the larvae fed by the extracts with organic solvents was significantly different in different solvents in 3-5 days.The corrected mortality of the ethyl acetate treatment was the highest（52.05%）,and the development period of the larvae treated by ethyl acetate was about 4-10 days longer than the control and the corresponding pupating rate was the lowest（43.30%）.Therefore,the effect of ethyl acetate extract was most significant.Moreover,the pupa weight of the treatments was little more than the control.The extracts from Cichorium intybus L.leaves had highest bioactivity mainly in anti-feeding activity on Mythimna separate Walker.

Synthesis, Characterization and Bioactivity of Complexes of Rare Earth with Bis-Schiff Base from Furoylpyrazolone

Eleven new complexes of rare earths with bis-Schiff base derived from N,N'-bis[(1-phenyl-3-methyl-5-oxo-4-pyrazolinyl) alpha-furylmethylidyne] ethylenediimine ((HPM alpha FP)(2)en) were synthesized. On the basis of elemental analysis and molar conductance, a general formula of the complexes, [RE(HPM alpha FP)(2)en(NO3)(2)]NO3(RE = La, Pr, Nd, Sm, Eu, Th, Dy, Ho, Er, Yb,Y), was given. The complexes were characterized by IR, UV-visible, H-1 NMR, C-13 NMR and fluorescence. The results show that the bis-Schiff base is a quadridentate ligand and the rare earth ions exhibit coordination of eight in the complexes. The antibacterial experiments indicate that they have high antibacterial activities against S. aureus, B. subtillis, E. coli, E. carotovora, C. flaccumfaciens.

Preparation by enzymolysis and bioactivity of iron complex of fish protein hydrolysate (Fe-FPH) from low value fish

Preparation of Fe^2＋ chelate of fish protein hydrolysate （Fe-FPH） obtained from low value fish proteins was introduced and its bioactivity was studied by compound enzymolysis. The optimum conditions for hydrolysate chelating Fe^2＋ are DH （degree of hydrolysis） at 5%, pH 7.0, 20℃ and 15 min chelating time for FM （material not being defatted）. Four types of Fe-FPH including CA （deposit after chelating）, CB （deposit in 50% of absolute ethanol solution）, CC （suspended deposit in 80% of absolute ethanol solution）, and CD （bottom deposit in 80% of absolute ethanol solution） were fractionated with absolute ethanol from FM. Structural analysis through infra-red spectrum revealed that Fe^2＋ was combined strongly with amino-group and carboxyl-group in each chelate and each Fe^2＋ could form two five-member ring structures. All of the four chelates were shown more significant antioxidative activity and can be used as natural hydrophobic and hydrophilic antioxidant. Among all the chelates, the CB possesses the most effective antioxidative activity at 92% as high as that of a-tocopherol. Among all Fe-FPHs, only CD showed the most effective antibacterial activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, and Bacillus subtilis and can be used as natural antibacterial. It provides a more effective way for utilization of low value fish proteins and key information of Fe-FPH as additive in food industry.

Isolation and characterization of anti-diabetic component(bioactivity-guided fractionation) from Ocimum sanctum L.(Lamiaceae) aerial part

Objective:To isolate and characterize antidiabetic component（bioactivity-guided fractionation） from hydro alcoholic extract of Ocimum sanctum（O.sanctum） aerial part.Methods:Ten fractions（F1 - F10） were isolated from hydro alcoholic extract of O.sanctum aerial part by column chromatography.All the fractions Fl to F10 were screened for antidiabetic activity in alloxan induced diabetic rats by estimating serum glucose level and lipid parameters.The isolated bioactive component was elucidated on the basis of extensive spectroscopic(UV,IR,MS,1H and 13C NMR) data analysis.Results:The bioactive fraction（F5） was found to be potent antidiabetic by ameliorating glucose and lipid parameters（total cholesterol,triglycerides,low and high density lipoprotein cholesterol）.The extensive spectroscopic data analysis reveals that,the isolated bioactive compound elucidated as tetracyclic triterpenoid[16-Hydroxy-4,4,10,13-tetramethyl- 17-（4-methyI-pentyl）-hexadecahydro-cyclopenta[a]phenanthren-3-one].Conclusions:Our present study concluded that,tetracyclic triterpenoid isolated from aerial part of O.sanctum has a great anti-diabetic potential.

Influence of mental stress on platelet bioactivity

It is well established that various mental stress conditions contribute, or at least influence, underlying pathophysiological mechanisms in somatic, as well as in psychiatric disorders; blood platelets are supposed to represent a possible link in this respect. The anculeated platelets are the smallest corpuscular elements circulating in the human blood. They display different serotonergic markers which seem to reflect the central nervous serotonin metabolism. They are known as main effectors in haematological processes but recent research highlights their role in the innate and adaptive immune system. Platelets are containing a multitude of pro-inflammatory and immune-modulatory bioactive compounds in their granules and are expressing immune-competent surface markers. Research gives hint that platelets activation and reactivity is increased by mental stress. This leads to enhanced cross talk with the immune system via paracrine secretion, receptor interaction and formation of platelet leucocyteaggregates. Recently it has been demonstrated that the immune system can have a remarkable impact in the development of psychiatric disorders. Thereforeplatelets represent an interesting research area in psychiatry and their role as a possible biomarker has been investigated. We review the influence of mental stress on what is termed platelet bioactivity in this article, which subsumes the mainly immune-modulatory activity of platelets in healthy volunteers, elderly persons with chronic care-giving strain, patients with cardiovascular diseases who are prone to psychosocial stress, as well as in patients with posttraumatic stress disorder. Research data suggest that stress enhances platelet activity, reactivity and immune-modulatory capacities.

In Situ Laser Coating of Calcium Phosphate on TC4 Surface for Enhancing Bioactivity

Titanium alloy has been a successful implant material owing to its excellent ratio of strength to weight, toughness, and bio-inert oxide surface. Significant progress has been made in improving the bioactivity of titanium alloy by coating its oxide surface with calcium phosphates. In the present study, in situ coating was reported on Ti6Al4V（TC4） surface with calcium phosphate （Ca-P） bioceramics synthesized and synchronously cladded by laser beam. This coating was grown by first preplacing directly the raw powders, which contain 80% of CaHPO4 · 2H2O, 20% of CaCO3, and dram of rare earth （RE）, on the TC4 surfaces, and then exposing the surfaces to the laser beam with a power density of 12. 73-15.27 MW · m^-2 and a scanning velocity of 10.5 m/s. The resultant coating was characterized using scanning electron microscopy （SEM）, X-ray diffraction （XRD）, thermogravimetric analysis and Different-thermal Scanning （TG-DSC）, and Energy Dispersive X-ray Detection （EDX）. The results show that these laser ceramics include hydroxyapatite （HA）, tricalcium phosphate （TCP）, Ca2 P2 O7, and other Ca-P phases, and the interface between the coating and the TC4 substrate has tighter fixation, in which the chemical bonding is approved. These laser hybrid coatings are useful in enhancing the bioactivity of titanium alloy surfaces.

Bioactivity,in-vitro corrosion behavior,and antibacterial activity of silver-zeolites doped hydroxyapatite coating on magnesium alloy

Mg-based alloys received significant attention for temporary implant applications while, their applications have been limited by high degradation rate. Therefore, silver-zeolite doped hydroxyapatite（Ag-Zeo-HAp） coating was synthesized on Ti O2-coated Mg alloy by physical vapour deposition（PVD） assisted electrodeposition technique to decrease the degradation rate of Mg alloy. X-ray diffraction（XRD） analysis and field emission scanning electron microscopy（FE-SEM） images showed the formation of a uniform and compact layer of Ag-Zeo-HAp with a thickness of 15 μm on the Ti O2 film with a thickness of 1 μm. The potentiodynamic polarization（PDP） and electrochemical impedance spectroscopy（EIS） tests indicated that corrosion resistance of Mg-Ca alloy was considerably increased by the Ag-Zeo-HAp coating. The bioactivity test in the simulated body fluid（SBF） solution showed that a dense and homogeneous bonelike apatite layer was formed on the Ag-Zeo-HAp surface after 14 d. Investigation of antibacterial activity via disk diffusion and spread plate methods showed that the Ag-Zeo-HAp coating had a significantly larger inhibition zone（3.86 mm） towards Escherichia coli（E. coli） compared with the Ti O2-coated Mg alloy（2.61 mm）. The Ag-Zeo-HAp coating showed high antibacterial performance, good bioactivity, and high corrosion resistance which make it a perfect coating material for biomedical applications.

Synthesis, Bioactivity and Crystal Structure Analysis of 2-(Benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) Acetamide

A novel benzisothiazolin-3-one derivative, 2-（benzo[d]isothiazol-3-yloxy）-N-（3- cyano-l-（4-fluorophenyl）-lH-pyrazol-5-yl） acetamide （8）, was synthesized from the initial compound benzo[d]isothiazol-3（2H）-one （BIT） 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed tile target compound exhibited a good anti-microbial activity.

Synthesis and bioactivity of a novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

A novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were synthesized by the condensation of 4-amino-5- [2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole with various(un)substituted aromatic acids in the presence of phosphorous oxychloride.These compounds were investigated for their inhibitory activity to E.coli methionine aminopeptidase(EcMetAP1).Some of the tested compounds showed significant inhibitory activity.

Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance

Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms.Resistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics.In order to overcome the resistance problem and to safely use antibiotics,the correct measurement of potency and bioactivity of antibiotics is essential.Microbiological assay and high performance liquid chromatography（HPLC） method are used to quantify the potency of antibiotics.HPLC method is commonly used for the quantification of potency of antibiotics,but unable to determine the bioactivity;whereas microbiological assay estimates both potency and bioactivity of antibiotics.Additionally,bioassay is used to estimate the effective dose against antibiotic resistant microbes.Simultaneously,microbiological assay addresses the several parameters such as minimal inhibitory concentration（MIC）,minimum bactericidal concentration（MBC）,mutation prevention concentration（MPC） and critical concentration（Ccr） which are used to describe the potency in a more informative way.Microbiological assay is a simple,sensitive,precise and cost effective method which gives reproducible results similar to HPLC.However,the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

BIOACTIVITY OF BIORESORBABLE OSTEOSYNTHETIC DEVICES MADE OF HYDROXYAPATITE/ POLY-DL-LACTIDE COMPOSITES: AN EXPERIMENTAL STUDY

Aim. To investigate the bioactivity of the self- designed biodegradable osteosynthetic devices made of resorbable hydroxyapatite microparticles/ poly- DL- lactide (HA/PDLLA) composites. Method. Forty- three rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod, the duration of follow- up were 3， 6， 12, 24 and 36 weeks. Histological, scanning electron microscopic (SEM), energy dispersive X- ray (EDX) and biomechanical analyses were done. Results. Active new bone formation and direct bone- bonding were seen at the bone- implant interface. Generous apatite crystals deposited and grew on the surface of the composites at 3～ 6 weeks postoperation. The interfacial shear strength increased significantly. Conclusion. Through the incorporating of resorbable HA microparticles, specific bone- bonding and active osteogenic capacity is introduced. This kind of bioactivity, together with other properties such as sufficient mechanical strength, enhanced biocompatibility and radiopacity, which are intrinsically unobtainable in totally resorbable polymer/polymer systems, make the HA/PDLLA composites become a desirable material for the internal fixation of cancellous bone.

Synthesis,Crystal Structure and Bioactivity of N-Phenethyl-4-hydroxy-4-phenyl Piperidine Hydrochloride

A novel compound N-phenethyl-4-hydroxy-4-phenyl piperidine hydrochloride （C19H24ClNO·H2O） has been synthesized and structurally characterized by elemental analysis, IR, ^1H NMR spectra and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 8.6306（8）, b = 11.0464（10）, c = 19.3221（18）A^°, V = 1842.1（3）A^°^3, Z = 4, Dc =1.211 g/cm^3,μ = 0.217 mm^-1, Mr= 335.86, F（000） = 720, S = 0.973, R = 0.0420 and wR = 0.1009 for 3627 unique reflections with 3157 observed ones （I 〉 2σ（I））. In the crystal, the dihedral angles made by piperidine ring with two benzene rings are 84.8（6） and 62.5（7）°, respectively. Intermolecular O-H…O and O-H…Cl hydrogen bonds involving water molecules form chains along the b axis, which stabilizes the crystal structure. The preliminary bioactivity tests indicated that the title compound has good effect of cellular growth inhibition to K562 cells and potential bioactivity of anti-leukemia.

Conceptual Density Functional Theory Study of the Chemical Reactivity Properties and Bioactivity Scores of the Leu-Enkephalin Opioid Peptide Neurotransmitter

The SMD solvation model (Solvation Model based on the Density) and eight density functionals, CAM-B3LYP, LC-ωPBE, M11, MN12SX, N12SX, ωB97, ωB97X, and ωB97XD, were assessed in link with the Def2TZVP basis set for the calculation of the structure of the Leu-Enkephalin Opioid Peptide Neurotransmitter as well as their molecular properties. Through the Conceptual Density Functional Theory (CDFT), the entire chemical descriptors for the system were calculated. The active regions of the molecules necessary for electrophilic, nucleophilic and radical attacks were chosen through linking them with the corresponding Fukui functions. Furthermore, the prediction of the pKa value for the peptide is done with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which comprises of a useful knowledge for the development of drugs for preventing Alzheimer, Diabetes and Parkinson diseases. Lastly, the bioactivity scores for the studied peptides are predicted via various methodologies.

Preparation and bioactivity of sol-gel macroporous bioactive glass

Bioactive glass is well known for its ability of bone regeneration, and sol-gel bioactive glass has many advantages compared with melt-derived bioactive glass. 3-D scaffold prepared by the sol-gel method is a promising substrate material for bone tissue engineering and large-scale bone repair. Porous sol-gel glass in the CaO-SiO2-P205 system with macropores larger than 100 μm was prepared by the addition of stearic acid as a pore former. The diameter of the pore created by the pore former varied from 100 to 300 μm. The formation of a hydroxyapatite layer on the glass was analyzed by studying the surface of the porous glass by scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Raman spectra after they had been immersed in simulated body fluid （SBF） for some time, and the porous glass shows good bioactivity.

Bioactivity of bioresorbable composite based on bioactive glass and poly-L-lactide

Bioactive and bioresorbable composite was fabricated by a solvent evaporation technique using poly-L-lactide(PLLA) and bioactive glass (average particle size: 6.8 μm). Bioactive glass granules are homogeneously distributed in the composite with microcrack structure. The formation of hydroxyapatite(HA) on the composite in simulated body fluid(SBF) was analyzed by scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS), X-ray diffraction(XRD), and Raman spectra. Rod-like HA crystals deposit on the surface of PLLA/bioactive glass composite after soaking for 3 d. Both rod-like crystals and HA layer form on the surface for 14 d in SBF. The high bioactivity of PLLA/bioactive glass composite indicates the potential of materials for integration with bone.