In vivo microCT-based time-lapse morphometry reveals anatomical site-specific differences in bone (re)modeling serving as baseline parameters to detect early pathological events

The bone structure is very dynamic and continuously adapts its geometry to external stimuli by modeling and remodeling the mineralized tissue. In vivo microCT-based time-lapse morphometry is a powerful tool to study the temporal and spatial dynamics of bone (re)modeling. Here an advancement in the methodology to detect and quantify site-specific differences in bone (re)modeling of 12-week-old BALB/c nude mice is presented. We describe our method of quantifying new bone surface interface readouts and how these are influenced by bone curvature. This method is then used to compare bone surface (re)modeling in mice across different anatomical regions to demonstrate variations in the rate of change and spatial gradients thereof. Significant differences in bone (re)modeling baseline parameters between the metaphyseal and epiphyseal are shown, as well as cortical and trabecular bone of the distal femur and proximal tibia. These results are validated using conventional static in vivo microCT analysis. Finally, the insights from these new baseline values of physiological bone (re)modeling were used to evaluate pathological bone (re)modeling in a pilot breast cancer bone metastasis model. The method shows the potential to be suitable to detect early pathological events and track their spatio-temporal development in both cortical and trabecular bone. This advancement in (re)modeling surface analysis and defined baseline parameters according to distinct anatomical regions will be valuable to others investigating various disease models with site-distinct local alterations in bone (re)modeling.ER

Alginate hydrogels for in vivo bone regeneration : the immune competence of the animal model matters

Biomaterials with tunable biophysical properties hold great potential for tissue engineering. The adaptive immune system plays an important role in bone regeneration. Our goal is to investigate the regeneration potential of cell-laden alginate hydrogels depending on the immune status of the animal model. Specifically, the regeneration potential of rat mesenchymal stromal cell (MSC)-laden, void-forming alginate hydrogels, with a stiffness optimized for osteogenic differentiation, is studied in 5 mm critical-sized femoral defects, in both T-cell deficient athymic RNU nude rats and immunocompetent Sprague Dawley rats. Bone volume fraction, bone mineral density and tissue mineral density are higher for athymic RNU nude rats 6 weeks post-surgery. Additionally, these animals show a significantly higher number of total cells and cells with non-lymphocyte morphology at the defect site, while the number of cells with lymphocyte-like morphology is lower. Hydrogel degradation is slower and the remaining alginate fragments are surrounded by a thicker fibrous capsule. Ossification islands originating from alginate residues suggest that encapsulated MSCs differentiate into the osteogenic lineage and initiate the mineralization process. However, this effect is insufficient to fully bridge the bone defect in both animal models. Alginate hydrogels can be used to deliver MSCs and thereby recruit endogenous cells through paracrine signaling, but additional osteogenic stimuli are needed to regenerate critical-sized segmental femoral defects

Beam-helicity asymmetries for single-hadron production in semi-inclusive deep-inelastic scattering from unpolarized hydrogen and deuterium targets

A measurement of beam-helicity asymmetries for single-hadron production in deep-inelastic scattering is presented. Data from the scattering of 27.6 GeV electrons and positrons off gaseous hydrogen and deuterium targets were collected by the HERMES experiment. The asymmetries are presented separately as a function of the Bjorken scaling variable, the hadron transverse momentum, and the fractional energy for charged pions and kaons as well as for protons and anti-protons. These asymmetries are also presented as a function of the three aforementioned kinematic variables simultaneously

Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome

Multiple synostoses syndrome 2 (SYNS2) is a rare genetic disease characterized by multiple fusions of the joints of the extremities, like phalangeal joints, carpal and tarsal joints or the knee and elbows. SYNS2 is caused by point mutations in the Growth and Differentiation Factor 5 (GDF5), which plays an essential role during skeletal development and regeneration. We selected one of the SYNS2-causing GDF5 mutations, p.N445T, which is known to destabilize the interaction with the Bone Morphogenetic Protein (BMP) antagonist NOGGIN (NOG), in order to generate the superagonistic GDF5 variant GDF5(N445T). In this study, we tested its capacity to support regeneration in a rat critical-sized defect model in vivo. MicroCT and histological analyses indicate that GDF5(N445T)-treated defects show faster and more efficient healing compared to GDF5 wild type (GDF5(wt))-treated defects. Microarray-based gene expression and quantitative PCR analyses from callus tissue point to a specific acceleration of the early phases of bone healing, comprising the inflammation and chondrogenesis phase. These results support the concept that disease-deduced growth factor variants are promising lead structures for novel therapeutics with improved clinical activities

One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration

Structured hydrogels showing form stability and elastic properties individually tailorable on different length scales are accessible in a one-step process. They support cell adhesion and differentiation and display growing pore size during degradation. In vivo experiments demonstrate their efficacy in biomaterial-induced bone regeneration, not requiring addition of cells or growth factors

Transverse-target-spin asymmetry in exclusive ω\omega-meson electroproduction

Hard exclusive electroproduction of $\omega$ mesons is studied with the HERMES spectrometer at the DESY laboratory by scattering 27.6 GeV positron and electron beams off a transversely polarized hydrogen target. The amplitudes of five azimuthal modulations of the single-spin asymmetry of the cross section with respect to the transverse proton polarization are measured. They are determined in the entire kinematic region as well as for two bins in photon virtuality and momentum transfer to the nucleon. Also, a separation of asymmetry amplitudes into longitudinal and transverse components is done. These results are compared to a phenomenological model that includes the pion pole contribution. Within this model, the data favor a positive $\pi\omega$ transition form factor.Comment: DESY Report 15-14

Longitudinal double-spin asymmetries in semi-inclusive deep-inelastic scattering of electrons and positrons by protons and deuterons

A comprehensive collection of results on longitudinal double-spin asymmetries is presented for charged pions and kaons produced in semi-inclusive deep-inelastic scattering of electrons and positrons on the proton and deuteron, based on the full HERMES data set. The dependence of the asymmetries on hadron transverse momentum and azimuthal angle extends the sensitivity to the flavor structure of the nucleon beyond the distribution functions accessible in the collinear framework. No strong dependence on those variables is observed. In addition, the hadron charge-difference asymmetry is presented, which under certain model assumptions provides access to the helicity distributions of valence quarks

Bose-Einstein correlations in hadron-pairs from lepto-production on nuclei ranging from hydrogen to xenon

Bose-Einstein correlations of like-sign charged hadrons produced in deep-inelastic electron and positron scattering are studied in the HERMES experiment using nuclear targets of $^1$H, $^2$H, $^3$He, $^4$He, N, Ne, Kr, and Xe. A Gaussian approach is used to parametrize a two-particle correlation function determined from events with at least two charged hadrons of the same sign charge. This correlation function is compared to two different empirical distributions that do not include the Bose-Einstein correlations. One distribution is derived from unlike-sign hadron pairs, and the second is derived from mixing like-sign pairs from different events. The extraction procedure used simulations incorporating the experimental setup in order to correct the results for spectrometer acceptance effects, and was tested using the distribution of unlike-sign hadron pairs. Clear signals of Bose-Einstein correlations for all target nuclei without a significant variation with the nuclear target mass are found. Also, no evidence for a dependence on the invariant mass W of the photon-nucleon system is found when the results are compared to those of previous experiments