Functional Scaffold‐Free Bone Equivalents Induce Osteogenic and Angiogenic Processes in a Human In Vitro Fracture Hematoma Model

After trauma, the formed fracture hematoma within the fracture gap contains all the important components (immune/stem cells, mediators) to initiate bone regeneration immediately. Thus, it is of great importance but also the most susceptible to negative influences. To study the interaction between bone and immune cells within the fracture gap, up-to-date in vitro systems should be capable of recapitulating cellular and humoral interactions and the physicochemical microenvironment (eg, hypoxia). Here, we first developed and characterized scaffold-free bone-like constructs (SFBCs), which were produced from bone marrow-derived mesenchymal stromal cells (MSCs) using a macroscale mesenchymal condensation approach. SFBCs revealed permeating mineralization characterized by increased bone volume (mu CT, histology) and expression of osteogenic markers (RUNX2, SPP1, RANKL). Fracture hematoma (FH) models, consisting of human peripheral blood (immune cells) mixed with MSCs, were co-cultivated with SFBCs under hypoxic conditions. As a result, FH models revealed an increased expression of osteogenic (RUNX2, SPP1), angiogenic (MMP2, VEGF), HIF-related (LDHA, PGK1), and inflammatory (IL6, IL8) markers after 12 and 48 hours co-cultivation. Osteogenic and angiogenic gene expression of the FH indicate the osteoinductive potential and, thus, the biological functionality of the SFBCs. IL-6, IL-8, GM-CSF, and MIP-1 beta were detectable within the supernatant after 24 and 48 hours of co-cultivation. To confirm the responsiveness of our model to modifying substances (eg, therapeutics), we used deferoxamine (DFO), which is well known to induce a cellular hypoxic adaptation response. Indeed, DFO particularly increased hypoxia-adaptive, osteogenic, and angiogenic processes within the FH models but had little effect on the SFBCs, indicating different response dynamics within the co-cultivation system. Therefore, based on our data, we have successfully modeled processes within the initial fracture healing phase in vitro and concluded that the cross-talk between bone and immune cells in the initial fracture healing phase is of particular importance for preclinical studies. (c) 2021 American Society for Bone and Mineral Research (ASBMR)

Comparison of nanoparticular hydroxyapatite pastes of different particle content and size in a novel scapula defect model

Nanocrystalline hydroxyapatite (HA) has good biocompatibility and the potential to support bone formation. It represents a promising alternative to autologous bone grafting, which is considered the current gold standard for the treatment of low weight bearing bone defects. The purpose of this study was to compare three bone substitute pastes of different HA content and particle size with autologous bone and empty defects, at two time points (6 and 12 months) in an ovine scapula drillhole model using micro-CT, histology and histomorphometry evaluation. The nHA-LC (38% HA content) paste supported bone formation with a high defect bridging-rate. Compared to nHA-LC, Ostim(®) (35% HA content) showed less and smaller particle agglomerates but also a reduced defect bridging-rate due to its fast degradation The highly concentrated nHA-HC paste (48% HA content) formed oversized particle agglomerates which supported the defect bridging but left little space for bone formation in the defect site. Interestingly, the gold standard treatment of the defect site with autologous bone tissue did not improve bone formation or defect bridging compared to the empty control. We concluded that the material resorption and bone formation was highly impacted by the particle-specific agglomeration behaviour in this study

Clinical application of scaffolds for cartilage tissue engineering

The purpose of this paper is to review the basic science and clinical literature on scaffolds clinically available for the treatment of articular cartilage injuries. The use of tissue-engineered grafts based on scaffolds seems to be as effective as conventional ACI clinically. However, there is limited evidence that scaffold techniques result in homogeneous distribution of cells. Similarly, few studies exist on the maintenance of the chondrocyte phenotype in scaffolds. Both of which would be potential advantages over the first generation ACI. The mean clinical score in all of the clinical literature on scaffold techniques significantly improved compared with preoperative values. More than 80% of patients had an excellent or good outcome. None of the short- or mid-term clinical and histological results of these tissue-engineering techniques with scaffolds were reported to be better than conventional ACI. However, some studies suggest that these methods may reduce surgical time, morbidity, and risks of periosteal hypertrophy and post-operative adhesions. Based on the available literature, we were not able to rank the scaffolds available for clinical use. Firm recommendations on which cartilage repair procedure is to be preferred is currently not known on the basis of these studies. Randomized clinical trials and longer follow-up periods are needed for more widespread information regarding the clinical effectiveness of scaffold-based, tissue-engineered cartilage repair

Les femmes alpinistes au Club Alpin Français (1874-1919) (un genre de compromis)

Le 2 avril 1874, avec la naissance du Club Alpin Français, l'institutionnalisation de l'alpinisme commence et sonne le début des "conquérants de l'inutile". Cette histoire, présentée comme universelle se conjugue-t-elle au féminin? Existe-t-il des "conquérantes de l'inutile" ? A partir des publications officielles du CAF, d'archives publiques et privées et de la presse sportive et féministe, ce travail questionne la spécificité de l'alpinisme féminin et permet de montrer les effets du genre. Ainsi, la masculinité de l'activité, les femmes sont non seulement intégrées au sein du CAF dès sa création mais en régulière progression entre 1874 et 1919. Leur investissement est cependant circonscrit dans une définition normative de l'excursionnisme féminin conforme aux représentations de la féminité de l'époque. Mais avec modération et sens du compromis, elles parviennent progressivement à sortir de ce modèle pour découvrir de nouveaux espaces et de nouvelles difficultés. Elles revendiquent et conquièrent de nouveaux droits mais sans jamais remettre en cause les hiérarchies entre les sexes et la spécificité de l'identité féminine. Ainsi, elles participent aux mutations de l'identité féminine vers une définition plus dynamique, plus instruite et plus libre. Malgré ces mutations, les plus conquérantes sont cependant toujours exclues de l'excellence alpine, nommé le sans-guide caractérisé par la prise de commandement, la tête de la cordée. Grâce à cette soumission à la domination masculine, les femmes alpinistes sont tolérées et initiées par les hommes et l'institution alpine. Le CAF participe à la construction d'une nouvelle femme cultivée, forte et vaillante, dévouée au service de la patrie mais soumise aux règles du genre. En donnant la parole ou le droit de vote aux femmes, en organisant l'instruction alpine des jeunes filles, il est foncièrement avant-gardiste par rapport aux autres associations sportives et participe à ce qu'il nomme le "sain féminisme"On April 2nd 1874, the Club Alpin Francais enters the alpine adventure. Mouniaineering is then officially recognized and marks the beginning of the "conquerants de l'inutile" - pioneers of useless conquests. Do women belong to this evolution? Do they also participate in this conquest? Based on officiaI materials published by the "CAF", on public and private archives, and on sports and feminist articles, this work questions the specificity of female mountaineering shows the effects of gender on the evolution of mountaineering. Therefore the male aspect of mountaineering, women are not only integrated within the CAF, right from the start, but their number is steadily increasing between 1874 and 1919. Women's involvement is nevertheless restricted to activities more appropriate with the contemporary representation of their status. They slowly manage to outgrow these boundaries to discover new frontiers and new difficulties. They claim and obtain new rights but without ever questioning hierarchy between genders and the female specificity. ln doing so they foment changes in the female identity toward a freer, more dynamic and more educated image. ln spite of these changes, the most adventurous ones do not gain access to the utmost revered position in mountaineering, called the " sans-guide ", which consists of leading the rope. This submissive attitude toward the male gender allows women to be tolerated and at the same time initiated by men and the alpine institution. The CAF participates in the creation of a new female persona, educated, strong and brave, devoted to her nation but following scrupulously the gender ruIes. By giving women the right of speech and vote, by organizing the training of young women, the CAF is ahead of its time with respect to other sports organizations. It participates in what it calls the "sane feminism"CHAMBERY -BU Bourget (730512101) / SudocSudocFranceF

Towards Higher-Precision Maneuver and Gust Loads Computations of Aircraft: Status of Related Features in the CFD-Based Multidisciplinary Simulation Environment FlowSimulator

It is common practice in aircraft industry to perform maneuver and gust loads computations on the basis of potential theory aerodynamics methods that neglect important physical effects. In order to master the future challenges of aviation, however, there is a need for higher-precision loads computations. For this and other purposes, the RANS-CFD-based multidisciplinary simulation environment FlowSimulator is being developed. The status of selected features of the environment related to higher-precision maneuver simulations is presented; example applications are discussed

Global Aero-Structural Design Optimization of More Flexible Wings for Commercial Aircraft

In the scope of the DLR project VicToria (Virtual Aircraft Technology Integration Platform), an integrated process for aero-structural wing optimization based on high fidelity simulation methods is continuously developed and applied. Based upon a parametric CAD model, flight performance under transonic flight conditions and maneuver loads are computed by solving the Reynolds-averaged Navier--Stokes equations (RANS). Structural mass and elastic characteristics of the wing are determined from structural sizing of the composite wing box for essential maneuver load cases using computational structural mechanics. Static aeroelastic effects are considered in all flight conditions by direct iterative coupling between the flow solver and the structural mechanics solver. Active maneuver load alleviation (MLA) is integrated in the process by a simplified modeling of control surface deflections by using a mesh deformation technique. Landing gear and control surface integration constraints were added compared to previous versions of the optimization process. Global aero-structural wing optimizations are successfully performed for wings with conventional composite wing box structure and for more flexible wings. The latter is accomplished by introducing modifications of the structural concept and the strain allowable. To reduce the CO2 emissions per passenger kilometer, the minimization of the combined fuel consumption for three typical flight missions represents the objective function. Wing optimizations are performed for variable and constant planform parameters as well as with and without consideration of MLA. A significant mass reduction of the optimized wing box is obtained with the more flexible wing concept, resulting in a drop in combined fuel consumption of about 3%. For wing optimizations with MLA the more flexible wing concept shows an additional reduction of the combined fuel consumption in the order of 2%. The more flexible wing concept results in optimized wing geometries with increased aspect ratio and reduced taper ratio