Bactericidal activity of gallium-doped chitosan coatings against staphylococcal infection.

AIMS: The aim of this study was to develop a new class of gallium (Ga)-doped chitosan (CS) coatings fabricated by electrophoretic deposition (EPD) in staphylococcal infection therapy. METHODS AND RESULTS: Biofilm formation on EPD CS/Ga coatings by Staphylococcus epidermidis and Staphylococcus aureus, which are the main strains involved in postarthroplasty infections, was assessed. The codeposition of an antibacterial agent was effective; Ga loaded into CS matrix reduces biofilm viability by up to 86% and 80% for S. epidermidis and S. aureus strains respectively. Lastly, the influence of pulsed electromagnetic field (PEMF) on the bactericidal activity of CS/Ga coatings was investigated in vitro. To this end, the coatings were incubated with S. epidermidis and S. aureus and exposed to the PEMF using two different frequencies and times. Biofilm viability for S. epidermidis was decreased by 35-40% in the presence of low-frequency (LF) and high-frequency (HF) PEMF respectively. Biofilm viability by S. aureus was not further reduced in the presence of LF PEMF, but decreased by 38% at HF PEMF. CONCLUSIONS: This study has established that a combination of PEMFs with the antibacterial agent improves bactericidal activity of Ga against S. epidermidis strain 14990 and S. aureus strain 12600. SIGNIFICANCE AND IMPACT OF THE STUDY: This new integrated approach could reduce the incidence of infection in orthopaedic implant applications. It also clearly demonstrates that the combination of Ga treatment with PEMF could aid biofilm-associated infection therapy due to improved Ga efficiency.

Microstructure and in vitro behaviour of 45S5 bioglass coatings deposited by high velocity suspension flame spraying (HVSFS).

The high-velocity suspension flame spraying technique (HVSFS) was employed in order to deposit 45S5 bioactive glass coatings onto titanium substrates, using a suspension of micron-sized glass powders dispersed in a water + isopropanol mixture as feedstock. By modifying the process parameters, five coatings with different thickness and porosity were obtained. The coatings were entirely glassy but exhibited a through-thickness microstructural gradient, as the deposition mechanisms of the glass droplets changed at every torch cycle because of the increase in the system temperature during spraying. After soaking in simulated body fluid, all of the coatings were soon covered by a layer of hydroxyapatite; furthermore, the coatings exhibited no cytotoxicity and human osteosarcoma cells could adhere and proliferate well onto their surfaces. HVSFS-deposited 45S5 bioglass coatings are therefore highly bioactive and have potentials as replacement of conventional hydroxyapatite in order to favour osseointegration of dental and prosthetic implants.

Observation of the naive-T-odd Sivers effect in deep-inelastic scattering.

Azimuthal single-spin asymmetries of leptoproduced pions and charged kaons were measured on a transversely polarized hydrogen target. Evidence for a naive-T-odd, transverse-momentum-dependent parton distribution function is deduced from nonvanishing Sivers effects for pi(+), pi(0), and K(+/-), as well as in the difference of the pi(+) and pi(-) cross sections.

Chitosan-Based Trilayer Scaffold for Multitissue Periodontal Regeneration.

Periodontal regeneration is still a challenge for periodontists and tissue engineers, as it requires the simultaneous restoration of different tissues-namely, cementum, gingiva, bone, and periodontal ligament (PDL). Here, we synthetized a chitosan (CH)-based trilayer porous scaffold to achieve periodontal regeneration driven by multitissue simultaneous healing. We produced 2 porous compartments for bone and gingiva regeneration by cross-linking with genipin either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze-drying the resulting scaffolds. We synthetized a third compartment for PDL regeneration by CH electrochemical deposition; this allowed us to produce highly oriented microchannels of about 450-µm diameter intended to drive PDL fiber growth toward the dental root. In vitro characterization showed rapid equilibrium water content for MMW-CH and LMW-CH compartments (equilibrium water content after 5 min >85%). The MMW-CH compartment degraded more slowly and provided significantly more resistance to compression (28% ± 1% of weight loss at 4 wk; compression modulus HA = 18 ± 6 kPa) than the LMW-CH compartment (34% ± 1%; 7.7 ± 0.8 kPa) as required to match the physiologic healing rates of bone and gingiva and their mechanical properties. More than 90% of all human primary periodontal cell populations tested on the corresponding compartment survived during cytocompatibility tests, showing active cell metabolism in the alkaline phosphatase and collagen deposition assays. In vivo tests showed high biocompatibility in wild-type mice, tissue ingrowth, and vascularization within the scaffold. Using the periodontal ectopic model in nude mice, we preseeded scaffold compartments with human gingival fibroblasts, osteoblasts, and PDL fibroblasts and found a dense mineralized matrix within the MMW-CH region, with weakly mineralized deposits at the dentin interface. Together, these results support this resorbable trilayer scaffold as a promising candidate for periodontal regeneration.

Miniaturized microdosimeters as LET monitors: First comparison of calculated and experimental data performed at the 62 MeV/u 12C beam of INFN-LNS with four different detectors.

PURPOSE: The aim of this paper is to investigate the limits of LET monitoring of therapeutic carbon ion beams with miniaturized microdosimetric detectors. METHODS: Four different miniaturized microdosimeters have been used at the 62 MeV/u 12C beam of INFN Southern National Laboratory (LNS) of Catania for this purpose, i.e. a mini-TEPC and a GEM-microdosimeter, both filled with propane gas, and a silicon and a diamond microdosimeter. The y-D (dose-mean lineal energy) values, measured at different depths in a PMMA phantom, have been compared withLET¯D (dose-mean LET) values in water, calculated at the same water-equivalent depth with a Monte Carlo simulation setup based on the GEANT4 toolkit. RESULTS: In these first measurements, no detector was found to be significantly better than the others as a LET monitor. The y-D relative standard deviation has been assessed to be 13% for all the detectors. On average, the ratio between y-D and LET¯D values is 0.9 ±â€¯0.3, spanning from 0.73 ±â€¯0.08 (in the proximal edge and Bragg peak region) to 1.1 ±â€¯0.3 at the distal edge. CONCLUSIONS: All the four microdosimeters are able to monitor the dose-mean LET with the 11% precision up to the distal edge. In the distal edge region, the ratio of y-D to LET¯D changes. Such variability is possibly due to a dependence of the detector response on depth, since the particle mean-path length inside the detectors can vary, especially in the distal edge region.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Microdosimetric Measurements in Gamma and neutron Fields with a Tissue Equivalent Proportional Counter Based on a Gas Electron Multiplier.

A multi-element tissue-equivalent proportional counter (TEPC), based on a single gas electron multiplier (GEM) foil of standard geometry, has been constructed with 16 cylindrical sensitives volumes. In this article, the design of this novel counter is described and first microdosimetric measurements are presented. To study the response of the GEM-TEPC to both low and high linear energy transfer radiation fields, the microdosimetric spectra due to a 137Cs gamma-ray source and to fast neutrons from 7Li(d,n)8Be reaction have been measured using pure propane gas at low pressure, in order to simulate a tissue site of about 1 µm equivalent size. The comparison with spectra measured with a spherical TEPC and with a mini-TEPC demonstrates promising properties for application of the GEM-TEPC for microdosimetric applications.

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane.

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported.

Bayesian reconstruction of nanodosimetric cluster distributions at 100% detection efficiency.

Ionisation spectra in nanometric volumes at a given distance from a charged particle track are obtained by using electron (or ion) gas detectors, having non-uniformly distributed detection efficiency. Therefore, such spectra should be properly processed in order to reconstruct the frequency distribution of clusters really produced in the detector gas. A Bayesian unfolding has been applied to ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained by Monte Carlo simulations, taking into account different detection efficiency conditions. It will be shown that Bayesian analysis provides a valid tool for reconstructing the true ionisation distributions, well beyond the maximum measured cluster size.

Two miniaturised TEPCS in a single detector for BNCT microdosimetry.

Microdosimetry with tissue-equivalent proportional counters (TEPC) has proven to be an ideal dosimetry technique for mixed radiation fields as those ones used in boron neutron capture therapy (BNCT). A new counter, composed of two twin cylindrical mini TEPCs inserted in a slim titanium sleeve of 2.7 mm external diameter, has been constructed. The detector has been designed to perform dosimetry and microdosimetry in intense radiation fields. The two mini TEPCs work in gas flow mode. They have right cylinder sensitive volumes of 0.9 mm. In spite of gas line tiny sizes, the gas pressure inside the two counters is well established with <1% of uncertainty. The counter has been calibrated in a secondary standard photon fields. The mean of the effective sensitive volume sizes has been measured to be 0.86 mm. The twin TEPC acquisition system processes properly the signals up to about 30 kHz of counting rate. Therefore, twin TEPC can perform dosimetric measurements in photon field with intensities of some tens of Gy h(-1).

MICRODOSIMETRIC MEASUREMENTS OF A TISSUE-EQUIVALENT PROPORTIONAL COUNTER BASED ON A GAS ELECTRON MULTIPLIER DOWN TO 140 nm SIMULATED SITE SIZES.

A multi-element tissue-equivalent proportional counter (TEPC), based on a gas electron multiplier, has been constructed with several cavities of small dimensions (down to 0.5 mm of diameter), to be used for microdosimetric measurements in intense, pulsed, radiation fields. First micro- and nano-dosimetric spectra with low-energy X rays in various simulated tissue site sizes are presented. The specific advantages and the calibration methods of this type of TEPC are discussed.

Bioactivity and Mechanical Stability of 45S5 Bioactive Glass Scaffolds Based on Natural Marine Sponges.

Bioactive glass (BG) based scaffolds (45S5 BG composition) were developed by the replica technique using natural marine sponges as sacrificial templates. The resulting scaffolds were characterized by superior mechanical properties (compression strength up to 4 MPa) compared to conventional BG scaffolds prepared using polyurethane (PU) packaging foam as a template. This result was ascribed to a reduction of the total scaffold porosity without affecting the pore interconnectivity (>99%). It was demonstrated that the reduction of total porosity did not affect the bioactivity of the BG-based scaffolds, tested by immersion of scaffolds in simulated body fluid (SBF). After 1 day of immersion in SBF, a homogeneous CaP deposit on the surface of the scaffolds was formed, which evolved over time into carbonate hydroxyapatite (HCA). Moreover, the enhanced mechanical properties of these scaffolds were constant over time in SBF; after an initial reduction of the maximum compressive strength upon 7 days of immersion in SBF (to 1.2 ± 0.2 MPa), the strength values remained almost constant and higher than those of BG-based scaffolds prepared using PU foam (<0.05 MPa). Preliminary cell culture tests with Saos-2 osteoblast cell line, namely direct and indirect tests, demonstrated that no toxic residues remained from the natural marine sponge templates and that cells were able to proliferate on the scaffold surfaces.

Bayesian analysis of data: reconstruction of track structure at 100% detection efficiency for a track-nanodosimetric counter.

An algorithmic reconstruction of the probability distribution of ionisation cluster-size formation from measurements performed with detectors having a non-uniform sensitive volume is presented. From such a data analysis, ionisation spectra, which correspond to a detection efficiency of 100% are extracted for the track-nanodosimetric counter at L.N.L.-I.N.F.N.

Design of a 10 nm electron collector for a track-nanodosimetric counter.

Recently we have developed a track-nanodosimetric counter, which is a gas detector that measures the distributions of electrons induced by a charged particle in nanometric volumes of tissue equivalent matter, positioned at different distances from the track. Sites equivalent to 20 and 24 nm were defined by means of an electron collector, which is a system of electrodes enclosing an almost wall-less cylindrical volume. In this paper, we present the design of a new electron collector that is able to simulate a volume as small as 10 nm in diameter.

Reconstruction of cluster distributions at 100% detection efficiency for a track-nanodosimetric counter through a Bayesian analysis.

A Bayesian unfolding has been applied to ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained using Monte Carlo simulations, taking into account different detection efficiency conditions. The ideal case of a target volume with uniform efficiency has been investigated to study the dependence of the reconstruction on prior distributions. A simplified approach has been used to treat the case of a target volume with non-uniformly distributed efficiency, like the sensitive volume of the track-nanodosimetric counter. Our results point out that Bayesian analysis provides a effective tool for reconstructing the true ionisation distributions, well beyond the maximum measured cluster size.

Mini-TEPCs for radiation therapy.

A mini-tissue-equivalent proportional-counter (TEPC) has been constructed to study the possibility to manufacture mini-counters without field-shaping tubes for radiation therapy. The mini-TEPC can be assembled with and without field-shaping tubes. It can be equipped with a mini-alpha source for a precise lineal energy calibration. After the positive conclusions of this study, a slim TEPC has been designed and constructed. The slim TEPC has an external diameter of only 2.7 mm. It has been tested with therapeutic proton beams and gamma ray sources.

BNCT microdosimetry at the tapiro reactor thermal column.

A thermal column is available for dosimetric and radiobiological studies by the fast reactor TAPIRO, located at the ENEA research centre Casaccia. The TAPIRO neutron field has been studied (in the frame of LNL BNCT project) with a tissue-equivalent proportional counter, which has worked alternatively with an ordinary tissue-equivalent cathode and with a boron-enriched cathode. Measurements have been performed with polyethylene caps of different thickness. Both the absorbed dose and the microdosimetric-calculated biological effective dose show a maximum at approximately 0.5 mg cm(-2) of depth. The different dose components have been calculated and the results are discussed.

Microdosimetric investigation at the therapeutic proton beam facility of CATANA.

Proton beams (62 Mev) are used by the Laboratori Nazionali del Sud of the Italian Institute of Nuclear Physics to treat eye melanoma tumours at the therapeutic facility called CATANA. A cylindrical slim tissue-equivalent proportional counter (TEPC) of 2.7 mm external diameter has been used to compare the radiation quality of two spread-out Bragg peaks (SOBP) at the CATANA proton beam.

First microdosimetric measurements with a TEPC based on a GEM.

A new type of mini multi-element tissue-equivalent proportional counter (TEPC) based on a gas electron multiplier (GEM) has been designed and constructed. This counter is in particular suitable to be constructed with a small sensitive volume so that it can be used for microdosimetry in intense pulsed radiation fields to measure the microdosimetric spectrum in the beam of, for instance, a clinical linear accelerator. The concept lends itself also for a mini multi-element version of the counter to be used for applications in which a high sensitivity is required. In this paper, we present the first microdosimetric measurements of this novel counter exposed to a 14 MeV monoenergetic neutron beam and a californium (252Cf) source for a counter cavity diameter of 1.8 mm simulating 1.0 microm tissue site size. The measured spectra showed an excellent agreement with spectra from the literature. The specific advantages of the TEPC-GEM are discussed.

Experimental equivalent cluster-size distributions in nanometric volumes of liquid water.

Ionisation cluster-size distributions in nanometric volumes of liquid water were determined for alpha particles at 4.6 and 5.4 MeV by measuring cluster-size frequencies in small gaseous volumes of nitrogen or propane at low gas pressure as well as by applying a suitable scaling procedure. This scaling procedure was based on the mean free ionisation lengths of alpha particles in water and in the gases measured. For validation, the measurements of cluster sizes in gaseous volumes and the cluster-size formation in volumes of liquid water of equivalent size were simulated by Monte Carlo methods. The experimental water-equivalent cluster-size distributions in nitrogen and propane are compared with those in liquid water and show that cluster-size formation by alpha particles in nitrogen or propane can directly be related to those in liquid water.