Flexible, Transparent, and Cytocompatible Nanostructured Indium Tin Oxide Thin Films for Bio-optoelectronic Applications.

Electrical stimulation has been used successfully for several decades for the treatment of neurodegenerative disorders, including motor disorders, pain, and psychiatric disorders. These technologies typically rely on the modulation of neural activity through the focused delivery of electrical pulses. Recent research, however, has shown that electrically triggered neuromodulation can be further enhanced when coupled with optical stimulation, an approach that can benefit from the development of novel electrode materials that combine transparency with excellent electrochemical and biological performance.

In vitro analysis of a physiological strain sensor formulated from a PEDOT:PSS functionalized carbon nanotube-poly(glycerol sebacate urethane) composite.

Biodegradable strain sensors able to undergo controlled degradation following implantation have recently received significant interest as novel approaches to detect pathological tissue swelling or non-physiological stresses. In this study, the physicomechanical, electrochemical and active pressure sensing behavior of an electrically conductive and biodegradable poly(glycerol sebacate urethane) (PGSU) composite, reinforced with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) functionalized carbon nanotubes (CNTs), was evaluated in vitro. Analysis of these PGSU-CNTs composites demonstrated that the incorporation of functionalized CNTs into a biodegradable elastomer resulted in enhanced mechanical strength, conductivity and tailored matrix biodegradation.

Electrical percolation in extrinsically conducting, poly(ε-decalactone) composite neural interface materials.

By providing a bidirectional communication channel between neural tissues and a biomedical device, it is envisaged that neural interfaces will be fundamental in the future diagnosis and treatment of neurological disorders. Due to the mechanical mismatch between neural tissue and metallic neural electrodes, soft electrically conducting materials are of great benefit in promoting chronic device functionality. In this study, carbon nanotubes (CNT), silver nanowires (AgNW) and poly(hydroxymethyl 3,4-ethylenedioxythiophene) microspheres (MSP) were employed as conducting fillers within a poly(ε-decalactone) (EDL) matrix, to form a soft and electrically conducting composite.

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 utilize these progenitor cells are particularly promising.

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.

Boron Nitride Nanotube Addition Enhances the Crystallinity and Cytocompatibility of PVDF-TrFE.

Analysis of the cellular response to piezoelectric materials has been driven by the discovery that many tissue components exhibit piezoelectric behavior . In particular, polyvinylidene fluoride and the trifluoroethylene co-polymer (PVDF-TrFE) have been identified as promising piezo and ferroelectric materials with applications in energy harvesting and biosensor devices. Critically, the modulation of the structural and crystalline properties of PVDF-TrFE through annealing processes and the addition of particulate or fibrous fillers has been shown to modulate significantly the materials electromechanical properties.

Analysis of a poly(ε-decalactone)/silver nanowire composite as an electrically conducting neural interface biomaterial.

Background: Advancement in polymer technologies, facilitated predominantly through chemical engineering approaches or through the identification and utilization of novel renewable resources, has been a steady focus of biomaterials research for the past 50 years. Aliphatic polyesters have been exploited in numerous biomedical applications including the formulation of soft-tissue sutures, bone fixation devices, cardiovascular stents etc. Biomimetic 'soft' polymer formulations are of interest in the design of biological interfaces and specifically, in the development of implantable neuroelectrode systems intended to interface with neural tissues.

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.

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.

Attenuated Glial Reactivity on Topographically Functionalized Poly(3,4-Ethylenedioxythiophene):P-Toluene Sulfonate (PEDOT:PTS) Neuroelectrodes Fabricated by Microimprint Lithography.

Following implantation, neuroelectrode functionality is susceptible to deterioration via reactive host cell response and glial scar-induced encapsulation. Within the neuroengineering community, there is a consensus that the induction of selective adhesion and regulated cellular interaction at the tissue-electrode interface can significantly enhance device interfacing and functionality in vivo. In particular, topographical modification holds promise for the development of functionalized neural interfaces to mediate initial cell adhesion and the subsequent evolution of gliosis, minimizing the onset of a proinflammatory glial phenotype, to provide long-term stability.

Publisher Correction: Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor.

In the version of this Article originally published, in Fig. 4f, the asterisk was missing; in Fig. 6a-c, the labels 'Wnt/β-catenin signalling', 'Wnt/Ca pathway' and 'ERK' and their associated lines/arrows were missing; and in Fig.

The Functional Response of Mesenchymal Stem Cells to Electron-Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity.

Cells directly probe and respond to the physicomechanical properties of their extracellular environment, a dynamic process which has been shown to play a key role in regulating both cellular adhesive processes and differential cellular function. Recent studies indicate that stem cells show lineage-specific differentiation when cultured on substrates approximating the stiffness profiles of specific tissues. Although tissues are associated with a range of Young's modulus values for bulk rigidity, at the subcellular level, tissues are comprised of heterogeneous distributions of rigidity.

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.

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

Neuroprosthetic technologies for therapeutic neuromodulation have seen major advances in recent years but these advances have been impeded due to electrode failure or a temporal deterioration in the device recording or electrical stimulation potential. This deterioration is attributed to an intrinsic host tissue response, namely glial scarring or gliosis, which prevents the injured neurons from sprouting, drives neurite processes away from the neuroelectrode and increases signal impedance by increasing the distance between the electrode and its target neurons. To address this problem, there is a clinical need to reduce tissue encapsulation of the electrodes in situ and improve long-term neuroelectrode function.

Diatoms: a biotemplating approach to fabricating drug delivery reservoirs.

Biotemplating is a rapidly expanding subfield that utilizes nature-inspired systems and structures to create novel functional materials, and it is through these methods that the limitations of current engineering practices may be advanced. The diatom is an exceptional template for drug delivery applications, owing largely to its highly-ordered pores, large surface area, species-specific architecture, and flexibility for surface modifications. Diatoms have been studied in a wide range of biomedical applications and their potential as the next frontier of drug delivery has yet to be fully exploited.

Biofunctionalisation of electrically conducting polymers.

During a single decade of research, evidence has emerged that glial scar formation around the electro-tissue interface drives neural loss and increases the signal impedance of the electrodes, compromising the efficiency of the stimulating systems. Studies with conducting polymers (CPs) as electrode coatings have shown enhanced tissue integration and electrode performance in situ through biochemical and physicomechanical functionalisation. In this review, recent findings on CP modifications are provided in the context of neurospecific biomaterials, shedding light on the valuable impact of multifunctionalised strategies for biomedical applications.

The role of microtopography in cellular mechanotransduction.

Mechanotransduction is crucial for cellular processes including cell survival, growth and differentiation. Topographically patterned surfaces offer an invaluable non-invasive means of investigating the cell response to such cues, and greater understanding of mechanotransduction at the cell-material interface has the potential to advance development of tailored topographical substrates and new generation implantable devices. This study focuses on the effects of topographical modulation of cell morphology on chromosomal positioning and gene regulation, using a microgrooved substrate as a non-invasive mechanostimulus.

Nanotopographical control of stem cell differentiation.

Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells.

Using immuno-scanning electron microscopy for the observation of focal adhesion-substratum interactions at the nano- and microscale in S-phase cells.

It is becoming clear that the nano/microtopography of a biomaterial in vivo is of first importance in influencing focal adhesion formation and subsequent cellular behaviour. When considering next-generation biomaterials, where the material's ability to elicit a regulated cell response will be key to device success, focal adhesion analysis is an useful indicator of cytocompatibility and can be used to determine functionality. Here, a methodology is described to allow simultaneous high-resolution imaging of focal adhesion sites and the material topography using field emission scanning electron microscopy.

Nanotopographical modification: a regulator of cellular function through focal adhesions.

Unlabelled: As materials technology and the field of biomedical engineering advances, the role of cellular mechanisms, in particular adhesive interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device design has evolved from the exquisite ability of biological systems to respond to topographical features or chemical stimuli, a process that has led to the development of next-generation biomaterials for a wide variety of clinical disorders. In vitro studies have identified nanoscale features as potent modulators of cellular behavior through the onset of focal adhesion formation.

The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+ enriched skeletal stem cells.

The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways.

Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage.

Polymeric medical devices widely used in orthopedic surgery play key roles in fracture fixation and orthopedic implant design. Topographical modification and surface micro-roughness of these devices regulate cellular adhesion, a process fundamental in the initiation of osteoinduction and osteogenesis. Advances in fabrication techniques have evolved the field of surface modification; in particular, nanotechnology has allowed the development of nanoscale substrates for the investigation into cell-nanofeature interactions.

Regulation of implant surface cell adhesion: characterization and quantification of S-phase primary osteoblast adhesions on biomimetic nanoscale substrates.

Integration of an orthopedic prosthesis for bone repair must be associated with osseointegration and implant fixation, an ideal that can be approached via topographical modification of the implant/bone interface. It is thought that osteoblasts use cellular extensions to gather spatial information of the topographical surroundings prior to adhesion formation and cellular flattening. Focal adhesions (FAs) are dynamic structures associated with the actin cytoskeleton that form adhesion plaques of clustered integrin receptors that function in coupling the cell cytoskeleton to the extracellular matrix (ECM).

Nanotopographical stimulation of mechanotransduction and changes in interphase centromere positioning.

We apply a recently developed method for controlling the spreading of cultured cells using electron beam lithography (EBL) to create polymethylmethacrylate (PMMA) substrata with repeating nanostructures. There are indications that the reduced cell spreading on these substrata, compared with planar PMMA, results from a reduced adhesivity since there are fewer adhesive structures and fewer of their associated stress fibres. The reduced cell spreading also results in a reduced nuclear area and a closer spacing of centrosomes within the nucleus, suggesting that the tension applied to the nucleus is reduced as would be expected from the reduction in stress fibres.