An aging evaluation of the bearing performances of glass fiber composite laminate in salt spray fog environment

The aim of the present paper is to assess the bearing performance evolution of pinned, glass-composite laminates due to environmental aging in salt-spray fog tests. Glass fibers/epoxy pinned laminates were exposed for up to 60 days in salt-spraying, foggy environmental conditions (according to ASTM B117 standard). In order to evaluate the relationship between mechanical failure mode and joint stability over increasing aging time, different single lap joints, measured by the changing hole diameter (D), laminate width (W) and hole free edge distance (E), were characterized at varying aging steps. Based on this approach, the property-structure relationship of glass-fibers/epoxy laminates was assessed under these critical environmental conditions. Furthermore, an experimental 2D failure map, clustering main failure modes in the plane E/D versus W/D ratios, was generated, and its cluster variation was analyzed at each degree of aging

Bone Resorption by Osteoclasts: Molecular Mechanism of Pyk2 dephosphorylation by Dynamin

poster abstractOsteoporosis is a bone disease that affects hundreds of millions of people worldwide and is characterized by low bone mass and structural deterioration of bone tissue which increases the risk of bone fracture, frailty, morbidity and mortality. Excessive bone loss is caused by osteoclasts which degrade the organic and inorganic components of bone. The specific aim of this study is to identify and characterize the signaling proteins in osteoclasts that are responsible for the bone resorbing activity of these cells. The non-receptor tyrosine kinase, Pyk2, is highly expressed in osteoclasts. Mice lacking Pyk2 have an increase in bone mass due to impairment in osteoclast function. It has been demonstrated that phosphorylation of Pyk2 at Y402 is very important for osteoclast spreading and bone resorption. Our group also reported that the GTPase dynamin controls osteoclast bone resorption in part by leading to the dephosphorylation of Pyk2, thus decreasing Pyk2’s kinase activity. In the current study we examined the intracellular mechanism by which dynamin regulates Pyk2 dephosphorylation. Our findings demonstrated that Pyk2 dephosphorylation is predominately due to GTPase activity of dynamin since expression of dynamin mutants that have reduced affinity for GTP or exhibit defective GTPase activity resulted in an increase in Pyk2 Y402 phosphorylation. We also found that that Pyk2 phosphorylation was rescued in the presence of phenyl arsine oxide (PAO), a chemical inhibitor of tyrosine phosphatases and our preliminary results indicate that the tyrosine phosphatase PTP-PEST is involved in the dynamin-mediated dephosphorylation of Pyk2. Understanding the intracellular mechanism that regulates osteoclast function may lead to the identification of novel proteins that can be targeted by anti-resorptive therapies to treat bone related diseases. Over the past few decades, bisphosphonates have played a significant role in the treatment of osteoporosis. Unfortunately, osteonecrosis of the jaw has been recently described as a harmful side effect of bisphosphonate therapy, emphasizing the need to develop alternative approaches to treat osteoporosis. Novel therapeutic approaches may one day involve inhibitors to tyrosine kinases such as Pyk2 or involve combination therapies where inhibitors are paired with bisphosphonates as a way to boost the efficacy of anti-resorptive therapies with fewer side-effects

Focal Adhesion Kinases in Adhesion Structures and Disease

Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases

Enhancement of osteoblast activity on nanostructured NiTi/hydroxyapatite coatings on additive manufactured NiTi metal implants by nanosecond pulsed laser sintering

Background: The osteoinductive behaviors of nitinol (NiTi)-based metal implants for bone regeneration are largely dependent on their surface composition and topology. Continuous-mode laser sintering often results in complete melting of the materials and aggregation of particles, which lack control of heat transfer, as well as microstructural changes during sintering of the nanocomposite materials. Methods: In the current study, in situ direct laser deposition was used to additively manufacture three-dimensional NiTi structures from Ni and Ti powders. The mechanical property of NiTi has been shown to be similar to bone. Nanosecond pulsed laser sintering process was then utilized to generate a nanoporous composite surface with NiTi alloy and hydroxyapatite (HA) by ultrafast laser heating and cooling of Ni, Ti, and HA nanoparticles mixtures precoated on the 3D NiTi substrates; HA was added in order to improve the biocompatibility of the alloy. We then studied the underlying mechanism in the formation of NiTi/HA nanocomposite, and the synergistic effect of the sintered HA component and the nanoporous topology of the composite coating. In addition, we examined the activity of bone-forming osteoblasts on the NiTi/HA surfaces. For this, osteoblast cell morphology and various biomarkers were examined to evaluate cellular activity and function. Results: We found that the nanoscale porosity delivered by nanosecond pulsed laser sintering and the HA component positively contributed to osteoblast differentiation, as indicated by an increase in the expression of collagen and alkaline phosphatase, both of which are necessary for osteoblast mineralization. In addition, we observed topological complexities which appeared to boost the activity of osteoblasts, including an increase in actin cytoskeletal structures and adhesion structures. Conclusion: These findings demonstrate that the pulsed laser sintering method is an effective tool to generate biocompatible coatings in complex alloy-composite material systems with desired composition and topology. Our findings also provide a better understanding of the osteoinductive behavior of the sintered nanocomposite coatings for use in orthopedic and bone regeneration applications

Validazione esterna di una scala di grading delle malformazioni artero-venose rotte (RAGS) in una coorte multicentrica di adulti

Introduzione. La scala di valutazione del gradind delle MAV rotte (RAGS) è stata recentemente validata nella popolazione pediatrica. Il nostro studio è finalizzato a valutarne la sua efficacia in una coorte multicentrica di adulti comparandola con altre scale comunemente utilizzate. Materiali e metodi. Abbiamo effettuato un'analisi retrospettiva sui pazienti ricoverati per MAV rotte in 5 dipartimenti di neurochirurgia dal 2012 al 2019. Nei pazienti inclusi è stata effettuata un'analisi di regressione standard e dell'area sottesa alla curva AUROC delle seguenti scale: emorragia intracerebrale (ICH), ICH associata a MAV (AVICH), Spetzler-Martin (SM), SM Supplementare (Supp-SM), Hunt e Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS) e RAGS al fine di valutare il valore predittivo nella variazioni cliniche stimate con la scala di Rankin modificata (mRS) categoriale e dicotomizzata in tre periodi di follow-up: entro i 6 mesi, da 6 mesi a 1 anno e oltre 1 anno.Risultati. Sono stati inclusi 61 pazienti con un'età media di 43,6 anni. Nella nostra analisi RAGS è risultata superiore alle altre scale prese in esame in tutti e tre i periodi follow-up. RAGS ha presentato un AUROC rispettivo nei tre periodi di follow-up di 0,78 (entro 6 mesi), 0,74 (tra 6 e 12 mesi) e 0,71(oltre 12 mesi) quando è stata applicata la mRS categoriale ed ha presentato un AUROC rispettivo di 0,79, 0,76 e 0,73 quando è stata applicata la mRS dicotomizzata. Conclusioni. RAGS costituisce una scala affidabile che predice i risultati clinici nelle MAV rotte negli adulti. Inoltre, RAGS ha dimostrato di mantenere il suo valore predittivo anche se applicata a dipartimenti di neurochirurgia con preferenze di trattamento diverse

Morphological and Structural Evaluation of Hydration/Dehydration Stages of MgSO4 Filled Composite Silicone Foam for Thermal Energy Storage Applications

Salt hydrates, such as MgSO4·7H2O, are considered attractive materials for thermal energy storage, thanks to their high theoretical storage density. However, pure salt hydrates present some challenges in real application due to agglomeration, corrosion and swelling problems during hydration/dehydration cycles. In order to overcome these limitations, a composite material based on silicone vapor-permeable foam filled with the salt hydrate is here presented. For its characterization, a real-time in situ environmental scanning electron microscopy (ESEM) investigation was carried out in controlled temperature and humidity conditions. The specific set-up was proposed as an innovative method in order to evaluate the morphological evolution of the composite material during the hydrating and dehydrating stages of the salt. The results evidenced an effective micro-thermal stability of the material. Furthermore, dehydration thermogravimetric/differential scanning calorimetric (TG/DSC) analysis confirmed the improved reactivity of the realized composite foam compared to pure MgSO4·7H2O.This work was partially funded by the Ministerio de Ciencia, Innovación y Universidades de España (RTI2018-093849-B-C31). This work was partially supported by ICREA under the ICREA Academia program

Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts

Bone loss is caused by the dysregulated activity of osteoclasts which degrade the extracellular bone matrix. The tyrosine kinase Pyk2 is highly expressed in osteoclasts, and mice lacking Pyk2 exhibit an increase in bone mass, in part due to impairment of osteoclast function. Pyk2 is activated by phosphorylation at Y402 following integrin activation, but the mechanisms leading to Pyk2 dephosphorylation are poorly understood. In the current study, we examined the mechanism of action of the dynamin GTPase on Pyk2 dephosphorylation. Our studies reveal a novel mechanism for the interaction of Pyk2 with dynamin, which involves the binding of Pyk2's FERM domain with dynamin's plextrin homology domain. In addition, we demonstrate that the dephosphorylation of Pyk2 requires dynamin's GTPase activity and is mediated by the tyrosine phosphatase PTP-PEST. The dephosphorylation of Pyk2 by dynamin and PTP-PEST may be critical for terminating outside-in integrin signaling, and for stabilizing cytoskeletal reorganization during osteoclast bone resorption

Tailored Torsion and Bending-Resistant Avian-Inspired Structures

The escalating demand for torsion- and bending-resistant structures paired with the need for more efficient use of materials and geometries, have led to novel bio-inspired ingenious solutions. However, lessons from Nature could be as inspiring as they are puzzling: plants and animals offer an enormous range of promising but hierarchically complex configurations. Avian bones are prominent candidates for addressing the torsional and bending issue. They present a unique intertwining of simple components: helicoidal ridges and crisscrossing struts, able to bear flexural and twisting actions of winds. Here, it is set how to harmonically move from the natural to the engineering level to formalize and analyze the biological phenomena under controlled design conditions. The effect of ridges and struts is isolated and combined toward tailored torsion and bending-resistant arrangements. Then the biological level is revisited to extrapolate the avian allometric design approach and is translated into multiscale lightweight structures at the engineering level. This study exploits the complexity of Nature and the scalability that characterizes the evolutionary design of bird bones through the design and fabrication versatility allowed by additive manufacturing technologies. This paves the way for exploring the transferability of the proposed solution at multiple engineering scales

A Pyk2 Inhibitor Incorporated into a PEGDA-Gelatin Hydrogel Promotes Osteoblast Activity and Mineral Deposition

Pyk2 is a non-receptor tyrosine kinase that belongs to the family of focal adhesion kinases. Studies from our laboratory and others demonstrated that mice lacking the Pyk2 gene (Ptk2B) have high bone mass, which was due to increased osteoblast activity, as well as decreased osteoclast activity. It was previously reported that a chemical inhibitor that targets both Pyk2 and its homolog FAK, led to increased bone formation in ovariectomized rats. In the current study, we developed a hydrogel containing poly(ethylene glycol) diacrylate (PEGDA) and gelatin which was curable by visible-light and was suitable for the delivery of small molecules, including a Pyk2-targeted chemical inhibitor. We characterized several critical properties of the hydrogel, including viscosity, gelation time, swelling, degradation, and drug release behavior. We found that a hydrogel composed of PEGDA1000 plus 10% gelatin (P1000:G10) exhibited Bingham fluid behavior that can resist free flowing before in situ polymerization, making it suitable for use as an injectable carrier in open wound applications. The P1000:G10 hydrogel was cytocompatible and displayed a more delayed drug release behavior than other hydrogels we tested. Importantly, the Pyk2-inhibitor-hydrogel retained its inhibitory activity against the Pyk2 tyrosine kinase, and promoted osteoblast activity and mineral deposition in vitro. Overall, our findings suggest that a Pyk2-inhibitor based hydrogel may be suitable for the treatment of craniofacial and appendicular skeletal defects and targeted bone regeneration