Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM. It was optimized that 60P samples with 60-65% porosity (bimodal distribution of macro- to micropore) with average pore size ~60 μm and higher interconnectivity, moderately high antibiotic adsorption efficiency (~49%) was ideal. Results after 42 days showed antibiotic released higher than MIC against S. aureus compared to parenteral treatment (2 injections a day for 6 weeks). In vivo drug pharmacokinetics and SEM on bone-defect interface proved superiority of CFS loaded porous bioactive glass implants over parenteral group based on infection eradication and new bone formation.     

Evaluating the quality of entity relationship models

Entity Relationship (E-R) models are at the core of logical database design. This paper describes the development of a model, associated metrics and methodology for assessing the quality of an E-R model. The model was developed by investigating into the causal relationships between ontological and behavioural factors influencing data quality. The methodology describes aggregation of the scores on various metrics to calculate an overall quality score for an E-R model, and use of the model to identify problem areas if the individual quality scores on different factors do not meet organizational standards. Further possible improvement of the model and future research issues are also discussed.     

Cefuroxime-impregnated calcium phosphates as an implantable delivery system in experimental osteomyelitis

The study aimed to investigate the effectiveness of porous calcium phosphates viz., hydroxyapatite (HAp) and a bi-phasic calcium phosphate (BCP) with predominately β-tricalcium phosphate (β-TCP) prepared by aqueous solution combustion method impregnated with cefuroxime axetil for the treatment of experimental osteomyelitis and compared with parenteral treatment. In vitro release of the drug was tested for its sustained elution characteristics for 21 days in PBS (pH 7.2) and measured by HPLC. In the in vivo study, bone infection was induced in tibia of rabbits by inoculation of 1 ml (3 × 10⁶) CFU Staphylococcus aureus. On the 21st day, after the development of osteomyelitis, six animals were treated by filling the cavity with cefuroxime-impregnated HAp blocks (Group II), six animals with the same drug-impregnated β-TCP (Group III) and in six others, only cefuroxime (15 mg/kg twice daily) was injected parenterally 6 weeks (Group IV). Group I with six animals was kept untreated. Histologically, the signs of infection were found to subside by 3 and 6 weeks. Radiological evaluation with cefuroxime-impregnated HAp and β-TCP pointed out the disappearance of sequestrum and existence of newly formed bony specules. Concentration of cefuroxime in bone and serum as estimated by HPLC showed highest value on day 21 itself which reduced marginally by day 42 in both the groups and these values were higher than minimum inhibitory concentration (MIC) against S. aureus. Our findings suggest that bi-phasic calcium phosphates with predominately β-TCP content is a very efficient carrier material for antibiotic compounds even for refractory infections by S. aureus.     

Application of design of experiment on electrophoretic deposition of glass-ceramic coating materials from an aqueous bath

A process for application of abrasion- or corrosion-resistant glass-ceramic coating materials on metal substrate by electrophoretic deposition technique in an aqueous medium has been described. The effects of various process parameters, e.g. coating material concentration, time of deposition, applied current, pH of the suspension and concentration of the polymeric dispersant on the deposition efficiency have been studied. The process has been studied using a 2³-factorial design technique of three independent variables; i.e. coating material concentration, applied current, and the time taken to achieve the best combination. The regression equation obtained explains the experimental results satisfactorily.     

Glass-ceramic glazes for future generation floor tiles

Glaze in the CaO–MgO–Al₂O₃–SiO₂ system was heated at 950–1190 °C for 2 h and characterized. X-ray diffraction showed that only trace amount of mullite was formed in the glass-ceramic glaze heated at 950 °C. Both mullite and α-cordierite were formed in the glass-ceramic glaze heated at 1050 °C as primary and secondary phases. Glass-ceramic glazes heated at 1120 °C and 1190 °C contained α-cordierite and mullite as major and minor phases. Rietveld analysis revealed that the amount of α-cordierite increased and mullite decreased with increasing heating temperature. Field emission scanning electron microscopy showed presence of mullite crystals dispersed within residual glassy phase in the glass-ceramic glazes heated at 950 °C and 1050 °C. In the microstructures of glass-ceramic glazes heated at 1120 °C and 1190 °C α-cordierite crystals were mainly appeared. Energy Dispersive X-ray analysis corroborated X-ray diffraction results. Vickers microhardness measurement demonstrated highest hardness (8.38 ± 0.07 GPa) of the glass-ceramic glaze heated at 1190 °C.     

In vitro and in vivo release of cefuroxime axetil from bioactive glass as an implantable delivery system in experimental osteomyelitis

The aim of this study was to evaluate the characterisation, in vitro and in vivo biocompatibility and antimicrobial activity of bioactive glass (BG) impregnated with an antibiotic. The BG was prepared by normal glass melting procedures as a controlled release device to treat experimental osteomyelitis. The study design was for prospective in vivo experimental study. Two sets of porous bioactive glass ceramic blocks (9 mm × 4 mm × 4 mm and 20 mm × 9 mm × 9 mm) were fabricated using bioactive glass powder and subsequently antibiotic cefuroxime axetil (CFA) (55 and 125 mg on an average) was impregnated in these two sets of blocks, respectively. Osteomyelitis was produced in the right tibia of the rabbits according to the model of Norden. After thorough in vitro characterization of the porous blocks [including X-ray diffraction (XRD), Fourier-transformed infra-red spectroscopy (FTIR), thorough chemical analysis by inductively coupled plasma-atomic emission spectra (ICP-AES) and field-emission scanning electron microscopy (FESEM)] and in vitro elution of the said drug, in vivo test was carried out with rabbit species split into two groups: (a) animals treated with CFA impregnated bioactive glass and (b) parenteral [intra muscular (IM)] administration of CFA. Histological, radiological and drug concentration in bone and serum (measured by HPLC) in both groups were carried out. HPLC technique was used for determination of concentration both in vitro and in vivo. Fabricated porous struts showed amorphous microstructure without formation of any crystallite. The elution of said drug was stopped after 6 days in vitro. Histological studies at 3 and 6 weeks revealed formation of well-developed lamellar bone and havarsian canal. Radiological evaluation pointed out disappearance of sequestrum and existence of newly formed bony specules. Concentration of cefuroxime axetil in bone and serum showed highest value on day 21 which reduced marginally by day 42 and these values were higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (known pathogen for chronic osteomyelitis). It could be concluded that the biodegradable antibiotic carrier system developed in this study proved to be an effective therapeutic approach toward an experimental model of osteomyelitis. Based particularly on the in vivo results of the study, this cefuroxime axetil incorporated bioactive glass blocks can be successfully used in clinical cases of osteomyelitis in veterinary as well as human orthopaedic surgery.     

Effect of fuel characteristics on synthesis of calcium hydroxyapatite by solution combustion route

The effect of fuel characteristics on the processing of nano sized calcium hydroxyapatite (HA) fine powders by the solution combustion technique is reported. Urea, glycine and glucose were used as fuels in this study. By using different combinations of urea and glycine fuels and occasional addition of small amounts of highly water-soluble glucose, the flame temperature (T _f) of the process as well as product characteristics could be controlled easily. The powders obtained by this modified solution combustion technique were characterized by XRD, FTIR spectroscopy, SEM, FESEM-EDX, particle size analyser (PSD) and specific surface area (SSA) measurements. The particle size of phase pure HA powder was found to be <20 nm in this investigation. The effects of glucose addition with stoichiometric (μ = 1) and fuel excess (μ > 1) urea and glycine precursor batches were investigated separately.     

Quantitative profiling of bacteriocins present in dairy-free probiotic preparations of Lactobacillus acidophilus by nanoliquid chromatography-tandem mass spectrometry

Bacteriocins are a heterogeneous group of ribosomally synthesized peptides or proteins with antimicrobial activity, produced predominantly by lactic acid bacteria, with potential applications as biopreservatives and probiotics. We describe here a novel strategy based on a bottom-up, shotgun proteomic approach using nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) with multiple fragmentation techniques for the quantitative profiling of bacteriocins present in the probiotic preparations of Lactobacillus acidophilus. A direct LC-MS/MS analysis with alternate collision-induced dissociation, high-energy collision dissociation, and electron-transfer dissociation fragmentation following a filter-assisted size-exclusion sample prefractionation has resulted in the identification of peptides belonging to 37 bacteriocins or related proteins. Peptides from lactacin F, helveticin J, lysin, avicin A, acidocin M, curvaticin FS47, and carocin D were predominant. The process of freeze drying under vacuum was observed to affect both the diversity and abundance of bacteriocins. Data acquisition using alternating complementary peptide fragmentation modes, especially electron-transfer dissociation, has significantly enhanced the peptide sequence coverage and number of bacteriocin peptides identified. Multi-enzyme proteolytic digestion was observed to increase the sample complexity and dynamic range, lowering the chances of detection of low-abundant bacteriocin peptides by LC-MS/MS. An analytical platform integrating size exclusion prefractionation, nanoLC-MS/MS analysis with multiple fragmentation techniques, and data-dependent decision tree-driven bioinformatic data analysis is novel in bacteriocin research and suitable for the comprehensive bioanalysis of diverse, low-abundant bacteriocins in complex samples.     

Studies on a novel bioactive glass and composite coating with hydroxyapatite on titanium based alloys: Effect of γ-sterilization on coating

A novel silicate based bioactive glass coating composition containing B₂O₃ and TiO₂ having matching thermal properties with that of Ti₆Al₄ V implants was developed and characterized. A conventional vitreous enamelling technique was used for coating small flat surface and curved surface of small rods. Hydroxyapatite (HAp) micro and nano-crystalline particles were used to prepare bioactive glass-HAp composite coating. Scratch testing was used to study the coating adhesion and its fracture behaviour under simulated conditions. As observed from scratch testing results, adhesion strength of the coating improved from 21 N normal load to 27 N and 32 N on addition of micro-HAp and nano HAp powder, respectively, to bioactive glass matrix. Further, sterilization of the coated samples with 25 kGy gamma irradiation substantially enhanced the adhesion of glass coating and HAp-composite coating.     

Interfacial properties of metallized alumina ceramics

An alumina ceramic material (purity-96%) was metallized by the conventional molybdenum-manganese (Mo-Mn) process in which an alumina substrate was coated with Mo-Mn paste and subsequently heat treated at 1400 °C for 10 min. During the entire process a moist H₂ and N₂ gas mixture (dew point-20 °C) with 3:1 ratio was passed continuously through the furnace. X-ray diffraction analysis of the metallized alumina substrate identified only molybdenum phase at the surface of the metallizing layer. The microstructural observations of the metallized alumina substrate were made by scanning electron microscopy. Energy dispersive X-ray analysis showed the elemental compositions along the cross-sectional region of the metallized alumina substrate. The adhesion of the metallic coatings on the alumina substrates was evaluated qualitatively by a scratch testing technique and quantitatively by an adhesion tester. Nanohardness measurements showed gradual change in the nanohardness values across the metallized alumina substrate.