Antioxidant functionalized polymer capsules to prevent oxidative stress

Polymeric capsules exhibit significant potential for therapeutic applications as microreactors, where the bio-chemical reactions of interest are efficiently performed in a spatial and time defined manner due to the encapsulation of an active biomolecule (e.g., enzyme) and control over the transfer of reagents and products through the capsular membrane. In this work, catalase loaded polymer capsules functionalized with an external layer of tannic acid (TA) are fabricated via a layer-by-layer approach using calcium carbonate as a sacrificial template. The capsules functionalised with TA exhibit a higher scavenging capacity for hydrogen peroxide and hydroxyl radicals, suggesting that the external layer of TA shows intrinsic antioxidant properties, and represents a valid strategy to increase the overall antioxidant potential of the developed capsules. Additionally, the hydrogen peroxide scavenging capacity of the capsules is enhanced in the presence of the encapsulated catalase. The capsules prevent oxidative stress in an in vitro inflammation model of degenerative disc disease. Moreover, the expression of matrix metalloproteinase-3 (MMP-3), and disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), which represents the major proteolytic enzymes in intervertebral disc, are attenuated in the presence of the polymer capsules. This platform technology exhibits potential to reduce oxidative stress, a key modulator in the pathology of a broad range of inflammatory diseases.This publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Programme under Grant Number 13/RC/2073. A.L. and J.R.S. would like to acknowledge the Basque Government (Department of Education, Language Policy and Culture) for a postdoctoral grant and project GIC IT-632-13 respectively. The Spanish Ministry of Industry and Competitiveness for project MAT 2013-45559-P is also acknowledged. S.T., M.L. and C.P. gratefully acknowledge the financial support provided by the University of Basel and the Swiss National Science Foundation (SNSF). A.P. and J.R.S would like to acknowledge the European Cooperation in Science and Technology (COST) Action iPROMEDAI project (TD 1305)

Effects of isothermal crystallization on the mechanical properties of a elastomeric medium chain length polyhydroxyalkanoate

In the present study, the relationship between molecular structure and mechanical properties for a medium chain length polyhydroxyalkanoate (mcl-PHA) composed of 3-hydroxyoctanoate and 3-hydroxyhexanoate was elucidated. The mcl-PHA was crystallized from the melt at four different temperatures between its glass transition and melting point (37, 21, 3 and −21 °C) and its molecular structure was analysed by means of differential scanning calorimetry (DSC) and wide-angle X-ray diffractometry (WAXD). The mechanical properties, which were analysed via tensile-tests and dynamic mechanical analysis (DMA), were clearly affected by the selected crystallization temperature and corresponding molecular structure of the polymer. In this sense, samples crystallized at 37, 21 and 3 °C displayed higher secant moduli calculated at 2% (E2% ∼ 20 MPa) than the sample crystallized at −21 °C (E2% ∼ 7 MPa) due to their higher crystallinity. Even if samples crystallized at 37, 21 and 3 °C had very similar degree of crystallinity, their secant moduli calculated at 50, 100 and 200% (E50%, E100% and E200%) and yield strength (σy) were clearly affected by the selected crystallization temperature, showing a positive correlation (i.e., higher crystallization temperatures and corresponding more ordered crystalline domains with narrower crystal distributions resulted in higher E50%, E100% and E200% values).The authors are thankful for funds from the Basque Government, Department of Education, Universities and Research (GIC12/161-IT-632-13) and the Spanish Ministry of Innovation and Competitiveness MINECO (MAT2013-45559-P)

A Self-Powered Piezo-Bioelectric Device Regulates Tendon Repair-Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motion-powered electromechanical stimulation of tendon tissue through piezo-bioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathy-associated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes.The work was supported by grants to MJPB from Science Foundation Ireland (16/BBSRC/3317), to MAFY from H2020 Marie Skłodowska-Curie Actions (898737) and grant from Science Foundation Ireland (SFI), co-funded under the European Regional Development Fund through Grant numbers 13/RC/2073 and 13/RC/2073_P2. The authors thank Dr. Oliver Carroll for technical assistance. SGIker technical services (UPV/EHU) are gratefully acknowledged for XRD and XPS support. The authors acknowledge the facilities and scientific and technical assistance of the Centre for Microscopy & Imaging at the National University of Ireland Galway, a facility that is funded by NUIG and the Irish Government's Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007–2013

Nanoscale neuroelectrode modification via sub-20 nm silicon nanowires through self-assembly of block copolymers

Neuroelectrodes are susceptible to deterioration via scar encapsulation following implantation. Biologically relevant nanosurfaces which mimic the biological length scale may prevent this deterioration via the modulation of protein adsorption and cell adhesion. Furthermore, nanotopography may significantly enhance electrode performance via enhanced charge transfer. Here we describe a self-assembly process for the production of aligned and dense arrays of silicon nanopillars using block copolymers[1]. We discuss the effect of the surface modifications on cell-substrate interaction in vitro and how they may enhance electrode charge transfer and improve neuron/electrode integratio

Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets

Translation of transplanted alginate-encapsulated pancreatic islets to treat type 1 diabetes has been hindered by inconsistent long-term efficacy. This loss of graft function can be partially attributed to islet dysfunction associated with the destruction of extracellular matrix (ECM) interactions during the islet isolation process as well as immunosuppression-associated side effects. This study aims at recapitulating islet-ECM interactions by the direct functionalization of alginate with the ECM-derived peptides RGD, LRE, YIGSR, PDGEA, and PDSGR. Peptide functionalization is controlled in a concentration-dependent manner and its presentation is found to be homogeneous across the microcapsule environment. Preweaned porcine islets are encapsulated in peptide-functionalized alginate microcapsules, and those encapsulated in RGD-functionalized alginate displays enhanced viability and glucose-stimulated insulin release. Effects are RGD-specific and not observed with its scrambled control RDG nor with LRE, YIGSR, PDGEA, and PDSGR. This study supports the sustained presentation of ECM-derived peptides in helping to maintain health of encapsulated pancreatic islets and may aid in prolonging longevity of encapsulated islet grafts

Polyhydroxyalkanoate/carbon nanotube nanocomposites: Flexible electrically conducting elastomers for neural applications

14Aim: Medium chain length-polyhydroxyalkanoate/multi-walled carbon nanotube (MWCNTs) nanocomposites with a range of mechanical and electrochemical properties were fabricated via assisted dispersion and solvent casting, and their suitability as neural interface biomaterials was investigated. Materials & methods: Mechanical and electrical properties of medium chain length-polyhydroxyalkanoate/MWCNTs nanocomposite films were evaluated by tensile test and electrical impedance spectroscopy, respectively. Primary rat mesencephalic cells were seeded on the composites and quantitative immunostaining of relevant neural biomarkers, and electrical stimulation studies were performed. Results: Incorporation of MWCNTs to the polymeric matrix modulated the mechanical and electrical properties of resulting composites, and promoted differential cell viability, morphology and function as a function of MWCNT concentration. Conclusion: This study demonstrates the feasibility of a green thermoplastic MWCNTs nanocomposite for potential use in neural interfacing applications.reservedmixedVallejo-Giraldo, Catalina; Pugliese, Eugenia; Larrañaga, Aitor; Fernandez-Yague, Marc A; Britton, James J; Trotier, Alexandre; Tadayyon, Ghazal; Kelly, Adriona; Rago, Ilaria; Sarasua, Jose-Ramon; Dowd, Eilís; Quinlan, Leo R; Pandit, Abhay; Biggs, Manus J.P.Vallejo Giraldo, Catalina; Pugliese, Eugenia; Larrañaga, Aitor; Fernandez Yague, Marc A; Britton, James J; Trotier, Alexandre; Tadayyon, Ghazal; Kelly, Adriona; Rago, ILARIA, CARMELA; Sarasua, Jose Ramon; Dowd, Eilís; Quinlan, Leo R; Pandit, Abhay; Biggs, Manus J. P

Nanovibrational Stimulation of Mesenchymal Stem Cells Induces Therapeutic Reactive Oxygen Species and Inflammation for Three- Dimensional Bone Tissue Engineering

There is a pressing clinical need to develop cell-based bone therapies due to a lack of viable, autologous bone grafts and a growing demand for bone grafts in musculoskeletal surgery. Such therapies can be tissue engineered and cellular, such as osteoblasts combined with a material scaffold. Because mesenchymal stem cells (MSCs) are both available and fast growing compared to mature osteoblasts, therapies that utilise these progenitor cells are particularly promising. We have developed a nanovibrational bioreactor that can convert MSCs into bone-forming osteoblasts in 2D and 3D but the mechanisms involved in this osteoinduction process remain unclear. Here, to elucidate this mechanism, we use increasing vibrational amplitude, from 30 nm (N30) to 90 nm (N90) amplitudes at 1000 Hz, and assess MSC metabolite, gene and protein changes. These approaches reveal that dose-dependent changes occur in MSCs’ responses to increased vibrational amplitude, particularly in adhesion and mechanosensitive ion channel expression, and that energetic metabolic pathways are activated, leading to low-level reactive oxygen species (ROS) production and to low-level inflammation, as well as to ROS- and inflammation-balancing pathways. These events are analogous to those that occur in the natural bone-healing processes. We have also developed a tissue engineered MSC-laden scaffold designed using cells’ mechanical memory, driven by the stronger N90 stimulation. These new mechanistic insights and cell-scaffold design are underpinned by a process that is free of inductive chemicals

Effects of Polydopamine Functionalization on Boron Nitride Nanotube Dispersion and Cytocompatibility

Boron nitride nanotubes (BNNTs) have unique physical properties, of value in biomedical applications; however, their dispersion and functionalization represent a critical challenge in their successful employment as biomaterials. In the present study, we report a process for the efficient disentanglement of BNNTs via a dual surfactant/polydopamine (PD) process. High-resolution transmission electron microscopy (HR-TEM) indicated that individual BNNTs become coated with a uniform PD nanocoating, which significantly enhanced dispersion of BNNTs in aqueous solutions. Furthermore, the cytocompatibility of PD-coated BNNTs was assessed in vitro with cultured human osteoblasts (HOBs) at concentrations of 1, 10, and 30 μg/mL and over three time-points (24, 48, and 72 h). In this study it was demonstrated that PD-functionalized BNNTs become individually localized within the cytoplasm by endosomal escape and that concentrations of up to 30 μg/mL of PD-BNNTs were cytocompatible in HOBs cells following 72 h of exposure

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial (vol 321, pg 2292, 2019)

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