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The activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation to kill infected target cells. For these issues, Th lymphocytes must be converted into Th effector cells after their stimulation through their surface receptors TCR/CD3 (by binding to peptide-major histocompatibility complex localized on antigen-presenting cells) and the CD4 co-receptor. After stimulation, Th cells proliferate and differentiate into subpopulations, like Th1, Th2 or Th17, with different functions during the adaptative immune response. Due to the central role of the activation of Th lymphocytes for an accurate adaptative immune response and considering recent preclinical advances in the use of nanomaterials to enhance T-cell therapy, we evaluated in vitro the effects of graphene oxide (GO) and two types of reduced GO (rGO15 and rGO30) nanostructures on the Th2 lymphocyte cell line SR.D10. This cell line offers the possibility of studying their activation threshold by employing soluble antibodies against TCR/CD3 and against CD4, as well as the simultaneous activation of these two receptors. In the present study, the effects of GO, rGO15 and rGO30 on the activation/proliferation rate of these Th2 lymphocytes have been analyzed by studying cell viability, cell cycle phases, intracellular content of reactive oxygen species (ROS) and cytokine secretion. High lymphocyte viability values were obtained after treatment with these nanostructures, as well as increased proliferation in the presence of rGOs. Moreover, rGO15 treatment decreased the intracellular ROS content of Th2 cells in all stimulated conditions. The analysis of these parameters showed that the presence of these GO and rGO nanostructures did not alter the response of Th2 lymphocytes. [ABSTRACT FROM AUTHOR]

Stimuli responsive materials are found in a broad range of applications, from energy harvesters to biomolecular sensors. Here, we report the production of poly (L-lactic acid) (PLLA) thin films that exhibit a mechanical stress responsive behaviour. By simply applying a mechanical stress through an AFM tip, a local electrical polarization was generated and measured by Kelvin Probe Force Microscopy. We showed that the magnitude of the stress generated electrical polarization can be manipulated by varying the thickness or crystallization state of the PLLA thin films. Besides exhibiting a mechanical stress-response behaviour with potential for energy harvesting and sensor applications, we show by AFM that these platforms react to mechanical forces with physiological relevance: interaction forces as low as a cell sheet migrating over a substrate or larger ones as the fluid induced stresses in bone tissue. In living tissues, as most mechanical stimuli are transduced as strain gradients for the anatomical structures, these mechanically responsive substrates can be used as ex vivo platforms to study the protein and cells response over a large range of electrical stimuli amplitude. As a proof of concept, selective adsorption of a human fibronectin was demonstrated by local patterning of the stimuli responsive PLLA films. Bioelectricity is inherent to the formation and repair of living tissues and electrical stimulation has been recognized for promoting regeneration. Given the proven beneficial effects of electric fields and the absence of a suitable method of stimulation, there is a clinical need for smart substrates, which can generate a polarization (charges) to promote tissue regeneration without the need of external devices. In this work, we report the fabrication of poly(L-lactic) acid platforms that exhibit a mechanical stress responsive behaviour when subjected to physiologically relevant forces. This behaviour can be tailored by varying the thickness or crystallization state of the PLLA films. We further demonstrate the biofunctionality of such platforms by exploiting the mechanically-induced charge for adhesion protein adsorption. [Display omitted] [ABSTRACT FROM AUTHOR]

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior. [ABSTRACT FROM AUTHOR]

Abstract: The use of functional materials, such as ferroelectrics, as platforms for tissue growth in situ or ex situ, is new and holds great promise. But the usage of materials in any bioapplication requires information on biocompatibility and desirably on bioactive behavior when bone tissue engineering is envisaged. Both requirements are currently unknown for many ferroelectrics. Herein the bioactivity of LiNbO3 and LiTaO3 is reported. The formation of apatite-like structures on the surface of LiNbO3 and LiTaO3 powders after immersion in simulated body fluid (SBF) for different soaking periods indicates their bioactive potential. The mechanism of apatite formation is suggested. In addition, the significant release of lithium ions from the ferroelectric powders in the very first minutes of soaking in SBF is examined and ways to overcome this likely hurdle addressed. [Copyright &y& Elsevier]