Cartilage repair using hydrogels: a critical review of in vivo experimental designs

Prova tipográfica This review analyzes the outcomes and technical aspects of in vivo studies published in the past decade using gels and hydrogels for cartilage repair. Using PubMed search engine, original research publications during the period of 2002/01/01 to 2015/04/30 identifi ed 115 published papers. Of these, 3 studies failed to fi nd a statistically significant improvement of treatment group as compared to control and 18 studies did not clearly identify hyaline-like cartilage formation in the treated groups. The most frequent repaired lesion was the rabbit acute full thickness trochlear defect, using a scaff old combining a gel or hydrogel and other material. One third of the scaff olds were cell-free (35%) and the majority of the studies did not use growth factors (71%). The present review may constitute a useful tool in design of future studies, as limitations of study designs are pointed and results in terms of translation to human application is discussed.ARTICULATE project 623 (QREN-13/SI/2011-23189

Amniotic fluid-derived stem cells for cardiovascular tissue engineering applications

Recent research has demonstrated that a population of stem cells can be isolated from amniotic fluid removed by amniocentesis that are broadly multipotent and non-tumorogenic. These amniotic fluid-derived stem cells (AFSC) could potentially provide an autologous cell source for treatment of congenital defects identified during gestation, particularly cardiovascular defects. In this review, the various methods of isolating, sorting and culturing AFSC are compared, along with techniques for inducing differentiation into cardiac myocytes and endothelial cells. Though research has not demonstrated complete and high yield cardiac differentiation, AFSC have been shown to effectively differentiate into endothelial cells and can effectively support cardiac tissue. Additionally, several tissue engineering and regenerative therapeutic approaches for the use of these cells in heart patches, injection after myocardial infarction, heart valves, vascularized scaffolds and blood vessels are summarized. These applications show great promise in the treatment of congenital cardiovascular defects, and further studies of isolation, culture, and differentiation of AFSC will help to develop their use for tissue engineering, regenerative medicine, and cardiovascular therapies

In vivo and in vitro study of resorbable magnesium wires for medical implants: Mg purity, surface quality, Zn alloying and polymer coating

Magnesium is an excellent material in terms of biocompatibility and its corrosion products can serve as an active source for new bone formation. However, localized corrosion and H2 generation limit the potential of Mg-based implants. Utilizing low-alloyed Mg-Zn wires can strongly reduce problems with large H2 bubbles and improve the mechanical properties considerably while maintaining excellent long-term biocompatibility. Acidic pickling and a polymer coating can be effectively used to lower the rate of in vivo degradation. In this work, microstructural, mechanical, and in vitro characterization of 250 um and 300 um extruded wires made from ultra-pure Mg, commercially pure Mg, Mg-0.15Zn, Mg-0.4Zn and Mg-1Zn was performed. Additionally, Mg-0.4Zn wires together with a variant coated with a copolymer of L-lactide and {\epsilon}-caprolactone were tested in vivo on artificially damaged Wistar rat femurs. Based on the observed Mg-induced osteogenesis, polymer-coated Mg wires with a small addition of Zn are a perspective material for bone-support applications, such as cerclage and fixation wires

Enhanced Growth and Osteogenic Differentiation of Human Osteoblast-Like Cells on Boron-Doped Nanocrystalline Diamond Thin Films

Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH4:H2 gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000±14,000 and 152,000±10,000 cells/cm2, respectively, compared to 113,000±10,000 cells/cm2 on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells

Probing Strangeness Hadronization with Event-by-Event Production of Multistrange Hadrons

This Letter presents the first measurement of event-by-event fluctuations of the net number (difference between the particle and antiparticle multiplicities) of multistrange hadrons Ξ- and Ξ ̄+ and its correlation with the net-kaon number using the data collected by the ALICE Collaboration in pp, p-Pb, and Pb-Pb collisions at a center-of-mass energy per nucleon pair sNN=5.02 TeV. The statistical hadronization model with a correlation over three units of rapidity between hadrons having the same and opposite strangeness content successfully describes the results. On the other hand, string-fragmentation models that mainly correlate strange hadrons with opposite strange quark content over a small rapidity range fail to describe the data

Multimuons in cosmic-ray events as seen in ALICE at the LHC

ALICE is a large experiment at the CERN Large Hadron Collider. Located 52 meters underground, its detectors are suitable to measure muons produced by cosmic-ray interactions in the atmosphere. In this paper, the studies of the cosmic muons registered by ALICE during Run 2 (2015–2018) are described. The analysis is limited to multimuon events defined as events with more than four detected muons (Nμ > 4) and in the zenith angle range 0◦ 100) obtained with QGSJET-II-04 and SIBYLL 2.3d is compatible with the data, while EPOS-LHC produces a significantly lower rate (55% of the measured rate). For both QGSJET-II-04 and SIBYLL 2.3d, the rate is close to the data when the composition is assumed to be dominated by heavy elements, an outcome compatible with the average energy Eprim ∼ 1017 eV of these events. This result places significant constraints on more exotic production mechanisms

Measurement of the production and elliptic flow of (anti)nuclei in Xe-Xe collisions at √sNN =5.44 TeV

Measurements of (anti)deuteron and (anti)He3 production in the rapidity range |y|<0.5 as a function of the transverse momentum and event multiplicity in Xe-Xe collisions at a center-of-mass energy per nucleon-nucleon pair of sNN=5.44 TeV are presented. The coalescence parameters B2 and B3 are measured as a function of the transverse momentum per nucleon. The ratios between (anti)deuteron and (anti)He3 yields and those of (anti)protons and pions are reported as a function of the mean charged-particle multiplicity density and compared with two implementations of the statistical hadronization model and with coalescence predictions. The elliptic flow of (anti)deuterons is measured for the first time in Xe-Xe collisions and shows features similar to those already observed in Pb-Pb collisions, i.e., the mass ordering at low transverse momentum and the meson-baryon grouping at intermediate transverse momentum. The production of nuclei is particularly sensitive to the chemical freeze-out temperature of the system created in the collision, which is extracted from a grand-canonical-ensemble-based thermal fit, performed for the first time including light nuclei along with light-flavor hadrons in Xe-Xe collisions. The extracted chemical freeze-out temperature Tchem=(154.2±1.1) MeV in Xe-Xe collisions is similar to that observed in Pb-Pb collisions and close to the crossover temperature predicted by lattice quantum chromodynamics calculations

Proton emission in ultraperipheral Pb-Pb collisions at TeV

The first measurements of proton emission accompanied by neutron emission in the electromagnetic dissociation (EMD) of Pb208 nuclei in the ALICE experiment at the Large Hadron Collider are presented. The EMD protons and neutrons emitted at very forward rapidities are detected by the proton and neutron zero degree calorimeters of the ALICE experiment. The emission cross sections of zero, one, two, and three protons accompanied by at least one neutron were measured in ultraperipheral Pb208-Pb208 collisions at a center-of-mass energy per nucleon pair sNN=5.02TeV. The 0p and 3p cross sections are described by the RELDIS model within their measurement uncertainties, while the 1p and 2p cross sections are underestimated by the model by 17-25%. According to this model, these 0p, 1p, 2p, and 3p cross sections are associated, respectively, with the production of various isotopes of Pb, Tl, Hg, and Au in the EMD of Pb208. The cross sections of the emission of a single proton accompanied by the emission of one, two, or three neutrons in EMD were also measured. The data are significantly overestimated by the RELDIS model, which predicts that the (1p,1n), (1p,2n), and (1p,3n) cross sections are very similar to the cross sections for the production of the thallium isotopes Tl206,205,204

Multiplicity dependence of Υ production at forward rapidity in pp collisions at s=13 TeV

The measurement of Υ(1S), Υ(2S), and Υ(3S) yields as a function of the charged-particle multiplicity density, dNch/dη, using the ALICE experiment at the LHC, is reported in pp collisions at s= 13 TeV. The Υ meson yields are measured at forward rapidity (2.5<4) in the dimuon decay channel, whereas the charged-particle multiplicity is defined at central rapidity (|η|<1). Both quantities are divided by their average value in minimum bias events to compute the self-normalized quantities. The increase of the self-normalized Υ(1S), Υ(2S), and Υ(3S) yields is found to be compatible with a linear scaling with the self-normalized dNch/dη, within the uncertainties. The self-normalized yield ratios of excited-to-ground Υ states are compatible with unity within uncertainties. Similarly, the measured double ratio of the self-normalized Υ(1S) to the self-normalized J/ψ yields, both measured at forward rapidity, is compatible with unity for self-normalized charged-particle multiplicities beyond one. The measurements are compared with theoretical predictions incorporating initial or final state effects

Common femtoscopic hadron-emission source in pp collisions at the LHC

The femtoscopic study of pairs of identical pions is particularly suited to investigate the effective source function of particle emission, due to the resulting Bose-Einstein correlation signal. In small collision systems at the LHC, pp in particular, the majority of the pions are produced in resonance decays, which significantly affect the profile and size of the source. In this work, we explicitly model this effect in order to extract the primordial source in pp collisions at root s = 13 TeV from charged pi-pi correlations measured by ALICE. We demonstrate that the assumption of a Gaussian primordial source is compatible with the data and that the effective source, resulting from modifications due to resonances, is approximately exponential, as found in previous measurements at the LHC. The universality of hadron emission in pp collisions is further investigated by applying the same methodology to characterize the primordial source of K-p pairs. The size of the primordial source is evaluated as a function of the transverse mass (m(T)) of the pairs, leading to the observation of a common scaling for both pi-pi and K-p, suggesting a collective effect. Further, the present results are compatible with the mT scaling of the p-p and p-Lambda primordial source measured by ALICE in high multiplicity pp collisions, providing additional evidence for the presence of a common emission source for all hadrons in small collision systems at the LHC. This will allow the determination of the source function for any hadron-hadron pairs with high precision, granting access to the properties of the possible final-state interaction among pairs of less abundantly produced hadrons, such as strange or charmed particles