Using chondroitin sulfate to improve the viability and biosynthesis of chondrocytes encapsulated in interpenetrating network (IPN) hydrogels of agarose and poly(ethylene glycol) diacrylate

We recently introduced agarose-poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN) hydrogels to cartilage tissue engineering that were able to encapsulate viable cells and provide a significant improvement in mechanical performance relative to its two constituent hydrogels. The goal of the current study was to develop a novel synthesis protocol to incorporate methacrylated chondroitin sulfate (MCS) into the IPN design hypothesized to improve cell viability and biosynthesis. The IPN was formed by encapsulating porcine chondrocytes in agarose, soaking the construct in a solution of 1:10 MCS:PEGDA, which was then photopolymerized to form a copolymer network as the second network. The IPN with incorporated CS (CS-IPN) (~0.5 wt%) resulted in a 4- to 5-fold increase in the compressive elastic modulus relative to either the PEGDA or agarose gels. After 6 weeks of in vitro culture, more than 50% of the encapsulated chondrocytes remained viable within the CS-modified IPN, in contrast to 35% viability observed in the unmodified. At week 6, the CS-IPN had significantly higher normalized GAG contents (347 ± 34 µg/µg) than unmodified IPNs (158 ± 27 µg/µg, P < 0.05). Overall, the approach of incorporating biopolymers such as CS from native tissue may provide favorable micro-environment and beneficial signals to cells to enhance their overall performance in IPNs

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells

Enabling Surgical Placement of Hydrogels through Achieving Paste-Like Rheological Behavior in Hydrogel Precursor Solutions

Hydrogels are a promising class of materials for tissue regeneration, but they lack the ability to be molded into a defect site by a surgeon because hydrogel precursors are liquid solutions that are prone to leaking during placement. Therefore, although the main focus of hydrogel technology and developments are on hydrogels in their crosslinked form, our primary focus is on improving the fluid behavior of hydrogel precursor solutions. In this work, we introduce a method to achieve paste-like hydrogel precursor solutions by combining hyaluronic acid nanoparticles with traditional crosslinked hyaluronic acid hydrogels. Prior to crosslinking, the samples underwent rheological testing to assess yield stress and recovery using linear hyaluronic acid as a control. The experimental groups containing nanoparticles were the only solutions that exhibited a yield stress, demonstrating that the nanoparticulate rather than the linear form of hyaluronic acid was necessary to achieve paste-like behavior. The gels were also photocrosslinked and further characterized as solids, where it was demonstrated that the inclusion of nanoparticles did not adversely affect the compressive modulus and that encapsulated bone marrow-derived mesenchymal stem cells remained viable. Overall, this nanoparticle-based approach provides a platform hydrogel system that exhibits a yield stress prior to crosslinking, and can then be crosslinked into a hydrogel that is capable of encapsulating cells that remain viable. This behavior may hold significant impact for hydrogel applications where a paste-like behavior is desired in the hydrogel precursor solution

Masonry dams : analysis of the historical profiles of Sazilly, Delocre and Rankine

The significant advances in masonry dam design that took place in the second half of the 19th century are analyzed and discussed within the context of the historical development of dam construction. Particular reference is made to the gravity dam profiles proposed by Sazilly, Delocre and Rankine, who pioneered the application of engineering concepts to dam design, basing the dam profile on the allowable stresses for the conditions of empty and full reservoir. These historical profiles are analyzed taking into consideration the present safety assessment procedures, by means of a numerical application developed for this purpose, based on limit analysis equilibrium methods, which considers the sliding failure mechanisms, the most critical for these structures. The study underlines the key role of uplift pressures, which was only addressed by Lévy after the accident of Bouzey dam, and provides a critical understanding of the original design concepts, which is essential for the rehabilitation of these historical structures.This work has been funded by FCT (Portuguese Foundation for Science and Technology) through the PhD grant SFRH/BD/43585/2008, for which the first author is grateful

Masks for COVID-19.

Sustainable solutions on fabricating and using a face mask to block the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread during this coronavirus pandemic of 2019 (COVID-19) are required as society is directed by the World Health Organization (WHO) toward wearing it, resulting in an increasingly huge demand with over 4 000 000 000 masks used per day globally. Herein, various new mask technologies and advanced materials are reviewed to deal with critical shortages, cross-infection, and secondary transmission risk of masks. A number of countries have used cloth masks and 3D-printed masks as substitutes, whose filtration efficiencies can be improved by using nanofibers or mixing other polymers into them. Since 2020, researchers continue to improve the performance of masks by adding various functionalities, for example using metal nanoparticles and herbal extracts to inactivate pathogens, using graphene to make masks photothermal and superhydrophobic, and using triboelectric nanogenerator (TENG) to prolong mask lifetime. The recent advances in material technology have led to the development of antimicrobial coatings, which are introduced in this review. When incorporated into masks, these advanced materials and technologies can aid in the prevention of secondary transmission of the virus

Governing social orders, unfolding rationality, and Jesuit accounting practices:A procedural approach to institutional logics

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CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases