Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopaedic devices. In this study, the FDA approved plastic polycaprolactone, was embossed with nanometric grooves and the response of primary and immortalised osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion, they formed more focal complexes and a lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalised cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin mediated FAK activation

Surface-modified piezoelectric copolymer poly(vinylidene fluoride–trifluoroethylene) supporting physiological extracellular matrixes to enhance mesenchymal stem cell adhesion for nanoscale mechanical stimulation

There is an unmet clinical need to provide viable bone grafts for clinical use. Autologous bone, one of the most commonly transplanted tissues, is often used but is associated with donor site morbidity. Tissue engineering strategies to differentiate an autologous cell source, such as mesenchymal stromal cells (MSCs), into a potential bone-graft material could help to fulfill clinical demand. However, osteogenesis of MSCs can typically require long culture periods that are impractical in a clinical setting and can lead to significant cost. Investigation into strategies that optimize cell production is essential. Here, we use the piezoelectric copolymer poly(vinylidene fluoride–trifluoroethylene) (PVDF-TrFE), functionalized with a poly(ethyl acrylate) (PEA) coating that drives fibronectin network formation, to enhance MSC adhesion and to present growth factors in the solid phase. Dynamic electrical cues are then incorporated, via a nanovibrational bioreactor, and the MSC response to electromechanical stimulation is investigated

Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor

Bone grafts are one of the most commonly transplanted tissues. However, autologous grafts are in short supply, and can be associated with pain and donor-site morbidity. The creation of tissue-engineered bone grafts could help to fulfil clinical demand and provide a crucial resource for drug screening. Here, we show that vibrations of nanoscale amplitude provided by a newly developed bioreactor can differentiate a potential autologous cell source, mesenchymal stem cells (MSCs), into mineralized tissue in 3D. We demonstrate that nanoscale mechanotransduction can stimulate osteogenesis independently of other environmental factors, such as matrix rigidity. We show this by generating mineralized matrix from MSCs seeded in collagen gels with stiffness an order of magnitude below the stiffness of gels needed to induce bone formation in vitro. Our approach is scalable and can be compatible with 3D scaffolds

Special focus on nanoscale regeneration

No abstract available

Chirality-sorted carbon nanotube films as high capacity electrode materials

Carbon nanomaterials show great promise for a wide range of applications due to their excellent physicochemical and electrical properties. Since their discovery, the state-of-the-art has expanded the scope of their application from scientific curiosity to impactful solutions. Due to their tunability, carbon nanomaterials can be processed into a wide range of formulations and significant scope exists to couple carbon structures to electronic and electrochemical applications. In this paper, the electrochemical performance of various types of CNT films, which differ by the number of walls, diameter, chirality and surface chemistry is presented. Especially, chirality-sorted (6,5)- and (7,6)-based CNT films are shown to possess a high charge storage capacity (up to 621.91 mC cm−2), areal capacitance (262 mF cm−2), significantly increased effective surface area and advantageous charge/discharge characteristics without addition of any external species, and outperform many other high capacity materials reported in the literature. The results suggest that the control over the CNT structure can lead to the manufacture of macroscopic CNT devices precisely tailored for a wide range of applications, with the focus on energy storage devices and supercapacitors. The sorted CNT macroassemblies show great potential for energy storage technologies to come from R&D laboratories into real life.K. K. and D. J. would like to thank National Science Center, Poland (under the Polonez program, grant agreement UMO-2015/19/P/ST5/03799) and the European Union\u27s Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreements 665778 and 713690). D. J. would also like to acknowledge the Rector of the Silesian University of Technology in Gliwice for funding the research in the framework of Pro-Quality grant (04/020/RGJ18/0057). This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 13/RC/2073. M. J. Biggs is also an SFI, Starting Investigator SIRG COFUND fellow (11/SIRG/B2135). Authors acknowledge ESPEFUM laboratory (at Institute of Physics – CSE, Silesian University of Technology) for access to XPS experimental setup

In vitro attenuation of astrocyte activation and neuroinflammation through ibuprofen-doping of poly(3,4-ethylenedioxypyrrole) formulations

Neuroinflammation is often associated with poor functional recovery and may contribute to or initiate the development of severe neurological disorders, such as epilepsy, Parkinson\u27s disease or Alzheimer\u27s disease. Ibuprofen (IBU), being one of the most commonly used non-steroidal anti-inflammatory drugs, is known to possess neuroprotective activity and serve as a promising therapeutic for the treatment of neuroinflammation. In this study, the potential of an IBU-loaded poly(3,4-ethylenedioxypyrrole) (PEDOP) matrix has been assessed as a neural interface material with an aim to control astrocyte activation and suppress neuroinflammation in vitro. Three types of drug immobilization protocols were investigated, leading to the fabrication of IBU-loaded PEDOP matrices exhibiting a broad spectrum of electrical characteristics, drug release profiles, as well as biological responses. Among all investigated PEDOP formulations, PEDOP matrices formed through a three-step immobilization protocol exhibited the highest charge storage capacity (30 ± 1 mC/cm2) as well as a double layer capacitance of 645.0 ± 51.1 µF, associated with a relatively enlarged surface area. Demonstrating a total drug loading capacity of 150 µg/ml and a release rate constant of 0.15 1/h, this coating formulation may be employed as a safe electrical conducting drug eluting system.This publication has emanated from research conducted with the financial support of Science Foundation Ireland and is cofunded under the European Regional Development Fund under Grant Number 13/RC/2073. This project has received funding from the European Union\u27s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 713690 and SFI Technology Innovation Development Programme, grant no.15/TIDA/2992. This work has been supported by the Polish National Science Centre in the framework of Sonata 2016/23/D/ST5/01306. 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\u27s Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007-2013

The synergistic effects of gold particles and dexamethasone on the electrochemical and biological performance of PEDOT neural interfaces

Although neural devices have shown efficacy in the treatment of neurodegenerative diseases, their functionality is limited by the inflammatory state and glial scar formation associated with chronic implantation. The aim of this study was to investigate neural electrode performance following functionalization with an anti-inflammatory coating derived from a conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) matrix doped with dexamethasone (Dex) and decorated with Au particles. Pristine PEDOT, PEDOT-Dex and their gold-decorated analogues (PEDOT/Au and PEDOT-Dex/Au) were formulated by electrochemical deposition and characterized with respect to electrode electrochemical properties, surface morphology and biocompatibility towards primary neural cells. Through a process of gold deposition, it was possible to eliminate the initial burst release observed in PEDOT-Dex and maintain a stable, stepwise increase in Dex elution over 7 days. The released amounts of Dex exceeded the concentrations considered as therapeutic for both PEDOT-Dex and PEDOT-Dex/Au. The results clearly indicated that the presence of either Dex or Au particles facilitated the outgrowth of neurites. Finally, it was shown that the application of composite materials, such as PEDOT-Dex/Au, is an efficient way to improve the efficacy of neural interfaces in vitro.This publication has emanated from research conducted with the financial support of the Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 13/RC/2073. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Maria Skłodowska-Curie grant agreement No 713690 and SFI Technology Innovation Development Programme, grant no. 15/TIDA/2992. This work has been supported by the National Science Centre in Poland in the framework of Sonata 2016/23/D/ST5/01306. The authors acknowledge the facilities and scientific and technical assistance of the Centre for Microscopy and 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

In vitro attenuation of astrocyte activation and neuroinflammation through ibuprofen-doping of poly(3,4-ethylenedioxypyrrole) formulations

Neuroinflammation is often associated with poor functional recovery and may contribute to or initiate the development of severe neurological disorders, such as epilepsy, Parkinson's disease or Alzheimer's disease. Ibuprofen (IBU), being one of the most commonly used non-steroidal anti-inflammatory drugs, is known to possess neuroprotective activity and serve as a promising therapeutic for the treatment of neuroinflammation. In this study, the potential of an IBU-loaded poly(3,4-ethylenedioxypyrrole) (PEDOP) matrix has been assessed as a neural interface material with an aim to control astrocyte activation and suppress neuroinflammation in vitro. Three types of drug immobilization protocols were investigated, leading to the fabrication of IBU-loaded PEDOP matrices exhibiting a broad spectrum of electrical characteristics, drug release profiles, as well as biological responses. Among all investigated PEDOP formulations, PEDOP matrices formed through a three-step immobilization protocol exhibited the highest charge storage capacity (30 ± 1 mC/cm2) as well as a double layer capacitance of 645.0 ± 51.1 µF, associated with a relatively enlarged surface area. Demonstrating a total drug loading capacity of 150 µg/ml and a release rate constant of 0.15 1/h, this coating formulation may be employed as a safe electrical conducting drug eluting system.This publication has emanated from research conducted with the financial support of Science Foundation Ireland and is cofunded under the European Regional Development Fund under Grant Number 13/RC/2073. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 713690 and SFI Technology Innovation Development Programme, grant no.15/TIDA/2992. This work has been supported by the Polish National Science Centre in the framework of Sonata 2016/23/D/ST5/01306. 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.peer-reviewe