Hydroxyapatite cages with aligned pores for bone grafting – Seeding of human osteoblast-like cells in vitro and their response in dynamic culture mode

Hydroxyapatite (HA) is a highly regarded synthetic bone graft material. Porous HA ceramics blocks are used to substitute harvested natural bone grafts. Being similar to bone mineral, HA material integrates with the host bone through surface osteointegration and slowly resorb along with the natural bone remodeling process. The blocks in use currently have random and tortuous pore structures. The present work explores the usefulness of cage-like HA ceramic design with end-to-end open pores, with the help of in vitro cell culture methods. Such a structure, on implantation, will take up the blood factors and cells and host the bone remodeling process inside the bulk of the cage, leading to early healing. In the study, HA samples with aligned through-pores were prepared and explored in vitro, with a focus on how the pores host the cells inside and to what level the cells maintain their activity. Human osteoblast-like cells (HOS) were used, at different seeding and culturing approaches. Cell seeding was done through (i) conventional large volume cell suspension, (ii) a confined mini chamber with a limited volume of cell suspension, and (iii) placing a concentrated drop of cell suspension directly on top of the scaffold. The third approach gave the best cell adhesion and proliferation, and hence used for further explorations. A dynamic culture system was designed in-house by bifurcating the cell culture wells using vertical inserts, holding the samples horizontally with their ends open to both sides, and making the media flow across using a rocker platform. The HOS cell adhesion, viability and proliferation were tested in the HA cages, in static and dynamic culture conditions, with conventional porous ceramics as the control. The cell infiltration was deeper and the cell viability over a period of 7 days was significantly higher in dynamic culture conditions in the test samples.     

Fabrication and characterization of In doped Li13.9Sr0.1Zn(GeO4+δ)4 electrolytes for proton-conducting solid oxide fuel cells

Li_13.9Sr_0.1Zn(GeO_4+δ)₄ (LSZG) materials can exhibit proton conduction by Li⁺/H⁺ ion exchange in hydrogen atmosphere. It can be used in solid oxide fuel cells (SOFCs) as an electrolyte. In this study, In³⁺ doped LSZG powders are synthesized by sol-gel method. X-ray diffraction, scanning electron microscopy, thermal gravimetric analyzer, and electrochemical impedance spectroscopy are used to investigate the effects of In doping on LSZG. All Li_13.9-xIn_xSr_0.1Zn(GeO_4+δ)₄ (LISZG, 0 ≤ x ≤ 0.3) ceramics exhibit the same phase with LSZG. The dopant of In promotes the sintering activity and Li⁺/H⁺ ion exchange rate of LSZG. The optimum doping of In is x = 0.2. At 600 °C, Li_13.7In_0.2Sr_0.1Zn(GeO_4+δ)₄ (0.2LISZG) shows a proton conductivity of 0.094 S/cm under 0.9 V direct current bias voltage. In addition, the single cell based on 0.2LISZG electrolyte is prepared, and it has been demonstrated that the practical utilization of 0.2LISZG in IT-SOFCs is feasible.     

Effect of sintering conditions on structural and morphological properties of Y- and Co-doped BaZrO3 proton conductors

BaZrO₃-based materials doped with a trivalent cation have excellent chemical stability and relatively high proton conductivity which makes them potential proton conducting oxide materials for various electrochemical device applications such as hydrogen processing, high-temperature electrolysis, and solid electrolyte in fuel cells. However, BaZrO₃ showed poor sinterability, requiring high sintering temperatures (1700–2100 °C) with longtime sintering (20–100 h) to achieve the desired microstructure and grain growth. This sintering problem can be solved by slightly doping BaZrO₃ with a sintering aid element. Therefore, in this study, two different zirconate proton conductors: BaZr_0·9Y_0·1O_3-α (BZY) and BaZr_0·955Y_0·03Co_0·015O_3-α (BZYC) were sintered in an air atmosphere and an oxygen atmosphere for 20 h in the temperature range of 1500–1640 °C. The sinterability was evaluated by analyzing the XRD diffraction patterns, lattice constant, lattice strain, crystallite size, relative density, open porosity, closed porosity, surface morphology, grain size, and grain boundary distribution, using the XRD, SEM, EDX, and Archimedes density measurement methods. It is concluded that in an oxygen atmosphere, sintering aid Co not only improves the relative density but also produces highly dense fine particles with clear grain boundaries which are promising for electrochemical hydrogen device applications.     

Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

Neutrophils in Tuberculosis: Cell Biology,Cellular Networking and Multitasking in Host Defense

Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis.     

Association of solid fuel use with risk of stunting in children living in China

Stunting adversely affects physical and mental outcomes of children. It has not been examined whether household air pollution from solid fuel combustion is a risk factor for stunting in children. In a total of 41,439 children aged 6-17 across China, height was measured using a unified protocol. Multivariable linear regression models and logistic regression models were used to assess the associations of solid fuel use for cooking/heating with stunting in children. Adjusted for covariates, cooking/heating with solid fuel was significantly associated with a lower z-score for height for age and sex (β = −0.21 [−0.32 to −0.09] and −0.17 [−0.31 to −0.03], respectively) and an increased risk of stunting with an estimated ORs of 1.34 [1.07~1.68] and 1.37 [1.02~1.83], respectively. The risk of stunting associated with solid fuel use was statistically significant in high-age children. And the effect was greater on girls than on boys, though the difference was not statistically significant. Our study suggested that Chinese children living in households using solid fuel had a significantly higher risk of stunting than those living in households using cleaner fuel.     

Constructing developable surfaces by wrapping cones and cylinders

We model developable surfaces by wrapping a planar figure around cones and cylinders. Complicated developables can be constructed by successive mappings using cones and cylinders of different sizes and shapes. We also propose an intuitive control mechanism, which allows a user to select an arbitrary point on the planar figure and move it to a new position. Numerical techniques are then used to find a cone or cylinder that produces the required mapping. Several examples demonstrate the effectiveness of our technique.     

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1–14 days) and thyroid hormone hypertrophic medium (T3, 15–28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs’ therapeutic effect on cartilage regeneration and hypertrophy suppression.     

La0.6Sr0.4Co0.2Fe0.8O3-δ nanofiber cathode for intermediate-temperature solid oxide fuel cells by water-based sol-gel electrospinning: Synthesis and electrochemical behaviour

Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La_0.6Sr_0.4Co_0.2Fe_0.8O_3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce_0.9Gd_0.1O_1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance R_p is 1.0 Ω cm². Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h.