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International audience; Nacre, also called mother-of-pearl, is a naturally occurring biomineral, largely studied by chemists, structural biologists, and physicists to understand its outstanding and diverse properties. Nacre is constituted of aragonite nanograins surrounded by organic matrix, and it has been established that the organic matrix is responsible for initiating and guiding the biomineralization process. The first challenge to study the organic matrix of nacre lays in its separation from the biomineral. Several extraction methods have been developed so far. They are categorized as either strong (e.g., decalcification) or soft (e.g., water, ethanol) and they allow specific extractions of targeted compounds. The structure of the nacreous organic matrix is complex, and it provides interesting clues to describe the mineralization process. Proteins, sugars, lipids, peptides, and other molecules have been identified and their role in mineralization investigated. Moreover, the organic matrix of nacre has shown interesting properties for human health. Several studies are investigating its activity on bone mineralization and its properties for skin care. In this review, we focus on the organic constituents, as lipids, sugars, and small metabolites which are less studied since present in small quantities.

As Associations of researchers active in advocacy activities, we are deeply humbled by the courage shown by Iranian people, and especially women, since the start of protests on September 16. As Associations which advocate for human rights, we wish to express our unreserved solidarity towards the women of Iran and Afghanistan, and all oppressed women living in the world, who suffer with their connationals from privation of human rights, and are further discriminated against because of their gender. As Associations which advocate for freedom to do research for all, we extend our solidarity to all researchers working in regions where academic and scientific freedom is not recognized and guaranteed, and where research can be a life-risk job. As Associations which advocate for research ethics and integrity, we support the freedom to do research for all researchers who adopt their research methods to question the existing social, economic and political status quo, independently from their national origin, their cultural identity and ideological background. Research as a crime The ongoing protests in Iran have raised the world public opinion’s attention over violation of human rights once again. We know that violation of human rights is a daily reality for people living in many countries. Many of them are researchers. Since the Islamic Revolution, a large number of researchers have been arrested, detained and tortured by the Iranian government because of their research activity and international networks. A case which has gained international attention, especially thanks to Amnesty International, is that of Ahmad Reza Djalali. But there are many cases to be mentioned one by one here: the phrase “academic prisoners” is used to indicate them collectively. Of course, it is not an exclusive Iranian practice: in Egypt in 2016, the Italian PhD candidate Giulio Regeni was arrested, tortured and killed, while Patrick Zaki is currently facing trial, as too many of his connationals. To be women and scholars is even more dangerous, especially in political contexts as the Iranian and Afghan ones, where the Institutions are enforcing measures that restrict women’s freedom and rights as humans, before that as scholars, as made evident by the recent decision of Afghan authorities to prevent women from accessing education. A criminalization of research to various degrees can be seen in other countries as well, for example in Turkey or in Poland and academic freedom is strongly threatened in other countries like in Hungary. Research as a tool for political change The relevance of the status of women and of that of gender roles in society is strongly highlighted by the case of the conspiracy theories on a so-called “gender ideology”. This ideology spreads widely, including in Europe, where political movements call to “protect the traditional family” or the “respect of the religious faith” in order to take action against the academic system and to restrict all scientific research linked with gender studies. We believe that because research is based on freedom of thought and expression, it provides citizens with ways to analyse and criticise social, economic, and political developments. Thus, it is dangerous for authoritarian regimes and for governments that, without being fully authoritarian, push their country towards a progressive restriction of freedoms. We believe that research practice and findings can always have political implications, and thus can be equally important tools for advocacy. For this reason, academic and scientific freedom must be protected, as a founding element of democracy, from those who want to silence it and control it. It is thus crucial that Research Performing and Research Funding Organisations, as well as individual researchers, make it their priority to respect and value academic integrity, while actively guaranteeing academic freedom as a human right. At the same time, we can not advocate for academic and scientific freedom without supporting and protecting the freedom of thought and of expression as citizens: scholars are not separated from society, and we believe that their knowledge must be accepted also in the public debate as intellectuals, and not only as specialist workers restricted to their own field. Among all cases, we cite here as an example the one that involved Turkish scholar Şebnem Korur Fincancı, highlighted by the Academic Freedom Monitoring Project of Scholars at Risk. European researchers advocate for concrete support to researchers persecuted for their research activity As researchers’ associations who advocate to protect research ethics and integrity, and against any restrictions to academic freedom,we believe that the global academic community needs to be open to different approaches. As European-based Associations, we feel the need to highlight our support for the freedom of all scholars to carry out research from their chosen cultural and/or political perspective in a safe and respectful environment. This is even more important for those scholars who are based in, or come from, non- Western countries: their perspective can be novel to the majority of the European academic community, and thus they may be more exposed to epistemic violence or injustice. We all need to ensure that this does not happen.

Introduction: Bone fractures remain a common injury. Nonunion fractures are often a serious complication where delays in tissue regeneration occur. The use of pulsed electromagnetic fields (PEMFs) ...

Osteoporosis is a skeletal disease characterized by bone loss and bone microarchitectural deterioration. The combination of smart materials and stem cells represents a new therapeutic approach. In the present study, highly porous scaffolds are prepared by combining the conducting polymer PEDOT:PSS with collagen type I, the most abundant protein in bone. The inclusion of collagen proves to be an effective way to modulate their mechanical properties and it induces an increase in scaffolds’ electrochemical impedance. The biomimetic scaffolds support neural crest-derived stem cell osteogenic differentiation, with no need for scaffold pre-conditioning contrarily to other reports.

Bioelectronics have made strides in improving clinical diagnostics and precision medicine. The potential of bioelectronics for bidirectional interfacing with biology through continuous, label-free monitoring on one side and precise control of biological activity on the other has extended their application scope to

Bone adaptation to spaceflight results in bone loss at weight bearing sites following the absence of the stimulus represented by ground force. The rodent hindlimb unloading model was designed to mimic the loss of mechanical loading experienced by astronauts in spaceflight to better understand the mechanisms causing this disuse-induced bone loss. The model has also been largely adopted to study disuse osteopenia and therefore to test drugs for its treatment. Loss of trabecular and cortical bone is observed in long bones of hindlimbs in tail-suspended rodents. Over the years, osteocytes have been shown to play a key role in sensing mechanical stress/stimulus via the ECM-integrin-cytoskeletal axis and to respond to it by regulating different cytokines such as SOST and RANKL. Colder experimental environments (~20–22°C) below thermoneutral temperatures (~28–32°C) exacerbate bone loss. Hence, it is important to consider the role of environmental temperatures on the experimental outcomes. We provide insights into the cellular and molecular pathways that have been shown to play a role in the hindlimb unloading and recommendations to minimize the effects of conditions that we refer to as confounding factors.

Purpose of Review Osteocytes are considered to be the cells responsible for mastering the remodeling process that follows the exposure to unloading conditions. Given the invasiveness of bone biopsies in humans, both rodents and in vitro culture systems are largely adopted as models for studies in space missions or in simulated microgravity conditions models on Earth. Recent Findings After a brief recall of the main changes in bone mass and osteoclastic and osteoblastic activities in space-related models, this review focuses on the potential role of osteocytes in directing these changes. The role of the best-known signalling molecules is questioned, in particular in relation to osteocyte apoptosis. Summary The mechanotransduction actors identified in spatial conditions and the problems related to fluid flow and shear stress changes, probably enhanced by the alteration in fluid flow and lack of convection during spaceflight, are recalled and discussed.

Bone exhibits piezoelectric properties. Thus, electrical stimulations such as pulsed electromagnetic fields (PEMFs) and stimuli-responsive piezoelectric properties of scaffolds have been investigated separately to evaluate their efficacy in supporting osteogenesis. However, current understanding of cells responding under the combined influence of PEMF and piezoelectric properties in scaffolds is still lacking. Therefore, in this study, we fabricated piezoelectric scaffolds by functionalization of polycaprolactone-tricalcium phosphate (PCL-TCP) films with a polyvinylidene fluoride (PVDF) coating that is self-polarized by a modified breath-figure technique. The osteoinductive properties of these PVDF-coated PCL-TCP films on MC3T3-E1 cells were studied under the stimulation of PEMF. Piezoelectric and ferroelectric characterization demonstrated that scaffolds with piezoelectric coefficient d₃₃ = −1.2 pC/N were obtained at a powder dissolution temperature of 100 °C and coating relative humidity (RH) of 56%. DNA quantification showed that cell proliferation was significantly enhanced by PEMF as low as 0.6 mT and 50 Hz. Hydroxyapatite staining showed that cell mineralization was significantly enhanced by incorporation of PVDF coating. Gene expression study showed that the combination of PEMF and PVDF coating promoted late osteogenic gene expression marker most significantly. Collectively, our results suggest that the synergistic effects of PEMF and piezoelectric scaffolds on osteogenesis provide a promising alternative strategy for electrically augmented osteoinduction. The piezoelectric response of PVDF by PEMF, which could provide mechanical strain, is particularly interesting as it could deliver local mechanical stimulation to osteogenic cells using PEMF. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Published version This research was funded by Ministry of Education-Singapore, grant MOE2016-T2-2-108; Nanyang Technological University, CHAIR PROFESSORSHIPS grant; Agency for Science, Technology, and Research, grant AMBM, A18A8b0059.

&nbsp, Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of viable, autologous bone grafts is limited making alternative cell-based strategies a promising therapeutic alternative. Adipose-derived stem cells (ASCs) are a readily available population of mesenchymal stem/stromal cells (MSCs) that can be isolated within minimally invasive surgery. This ease of availability and their ability to undergo osteogenic differentiation makes ASCs promising candidates for cell-based therapies for bone fractures. Recent studies have suggested that both exposure to electrical fields and cultivation in 3D can positively affect osteogenic potential of MSCs. To elucidate the osteoinductive potential of a combination of these biophysical cues on ASCs, cells were embedded within anionic nanofibrillar cellulose (aNFC) hydrogels and exposed to electrical stimulation (ES) for up to 21 days. ES was applied to ASCs in 2D and 3D at a voltage of 0.1 V/cm with a duration of 0.04 ms, and a frequency of 10 Hz for 30 min per day. Exposure of ASCs to ES in 3D resulted in high alkaline phosphatase (ALP) activity and in an increased mineralisation evidenced by Alizarin Red S staining. Moreover, ES in 3D aNFC led to an increased expression of the osteogenic markers osteopontin and osteocalcin and a rearrangement and alignment of the actin cytoskeleton. Taken together, our data suggest that a combination of ES with 3D cell culture can increase the osteogenic potential of ASCs. Thus, exposure of ASCs to these biophysical cues might improve the clinical outcomes of regenerative therapies in treatment of osteoporotic fractures.

Conducting polymer scaffolds can promote cell growth by electrical stimulation, which is advantageous for some specific type of cells such as neurons, muscle, or cardiac cells. As an additional feature, the measure of their impedance has been demonstrated as a tool to monitor cell growth within the scaffold. In this work, we present innovative conducting polymer porous scaffolds based on poly(3,4-ethylenedioxythiophene) (PEDOT):xanthan gum instead of the well-known PEDOT:polystyrene sulfonate scaffolds. These novel scaffolds combine the conductivity of PEDOT and the mechanical support and biocompatibility provided by a polysaccharide, xanthan gum. For this purpose, first, the oxidative chemical polymerization of 3,4-ethylenedioxythiophene was carried out in the presence of polysaccharides leading to stable PEDOT:xanthan gum aqueous dispersions. Then, by a simple freeze-drying process, porous scaffolds were prepared from these dispersions. Our results indicated that the porosity of the scaffolds and mechanical properties are tuned by the solid content and formulation of the initial PEDOT:polysaccharide dispersion. Scaffolds showed interconnected pore structure with tunable sizes ranging between 10 and 150 μm and Young's moduli between 10 and 45 kPa. These scaffolds successfully support three-dimensional cell cultures of MDCK II eGFP and MDCK II LifeAct epithelial cells, achieving good cell attachment with very high degree of pore coverage. Interestingly, by measuring the impedance of the synthesized PEDOT scaffolds, the growth of the cells could be monitored.

Stem cell osteogenic differentiation is a complex process, associated with a number of events such as the secretion of collagen type I, osteopontin, osteonectin, osteocalcin and Bone Morphogenic Protein 2 (BMP-2). These molecules can be used as markers to monitor stem cell fate while studying the effects of a specific osteogenic differentiation treatment (e.g. electrical stimulation). Currently available techniques, such as the evaluation of the expression levels of specific genes and end-point biochemical assays, do not allow real-time monitoring of cellular processes, therefore overlooking potentially interesting information. This study explores a promising functionalization strategy towards on-line electrical monitoring of stem cell osteogenic differentiation process, using an organic electrochemical transistor (OECT) to detect cytokines of interest, secreted by cells during the osteogenic differentiation process, such as BMP-2. In this work, antibodies against BMP-2 were anchored on the poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) gate electrode of an OECT. The biofunctionalization process was evaluated using multiple techniques such as atomic force microscopy, electrochemical Raman spectroscopy, quartz crystal microbalance. Electrode properties were assessed by running chronoamperometric studies, as well as by characterizing the PEDOT:PSS thin film resistance to ion flow by electrochemical impedance spectroscopy and OECT performance using transient (AC) measurements. Finally, a proof-of-concept, biosensor measurement was performed to test our functionalization strategy for sensing, proving that the antibody-functionalized OECTs were able to detect recombinant BMP-2 at levels that are comparable to those used for in vitro stimulation of bone regeneration via soluble osteoinductive factors.

Cell fate is largely determined by interactions that occur at the interface between cells and their surrounding microenvironment. For this reason, especially in the field of tissue-engineering, there is a growing interest in developing techniques that allow evaluating cell–material interaction at the nanoscale, particularly focusing on cell adhesion processes. While for 2D culturing systems a consolidated series of tools already satisfy this need, in 3D environments, more closely recapitulating complex in vivo structures, there is still a lack of procedures furthering the comprehension of cell–material interactions. Here, the use of scanning electron microscopy coupled with a focused ion beam (SEM/FIB) for the characterization of cell interactions with 3D scaffolds obtained by different fabrication techniques is reported for the first time. The results clearly show the capability of the developed approach to preserve and finely resolve scaffold–cell interfaces highlighting details such as plasma membrane arrangement, extracellular matrix architecture and composition, and cellular structures playing a role in cell adhesion to the surface. It is anticipated that the developed approach will be relevant for the design of efficient cell-instructive platforms in the study of cellular guidance strategies for tissue-engineering applications as well as for in vitro 3D models.

Cell fate is largely determined by interactions that occur at the interface between cells and their surrounding microenvironment. For this reason, especially in the field of cell- and tissue-engineering, there is a growing interest in developing characterization techniques that allow a deep evaluation of cell-material interaction at the nanoscale, particularly focusing on cell adhesion processes. While for 2D culturing systems a consolidated series of tools already satisfy this need, in 3D environments, more closely recapitulating complex in vivo structures, there is still a lack of procedure furthering the comprehension of cell-material interactions. Here, we report for the first time the use of a SEM/FIB system for the characterization of cellular adhesion in 3D scaffolds fabricated by means of different techniques. Our results clearly show the capability of the developed approach to finely resolve both scaffold-cells interface and nanometer scale features of cell bodies involved in the upregulation of cellular behavior. These results are relevant for studying cellular guidance strategies and for the consequent design of more efficient cell-instructive platforms for tissue-engineering applications as well as for in vitro 3D models.

The use of adult stem/progenitor cells is a challenge in current research about kidney functional regeneration. In this framework, material-induced stem cell differentiation can become a new paradigm to promote advances in therapies. Here, the effects of both isotropic and anisotropic fibrous topographies on the podocyte differentiation of adult renal stem cells (RSCs) from human donors are investigated. The proliferation rate of RSCs is analyzed, immunofluorescence and genetic analyses of specific podocyte markers (Wilms' tumor 1 gene, nephrin, and podocin) are performed to assess the differentiation level on the scaffolds. The studied markers are over-expressed in RSCs cultured on aligned fibers compared to cells cultured on either protein-functionalized films or randomly oriented fibers. In addition, RSCs cultured on aligned fibers are found to differentiate toward podocyte precursors even in basal medium conditions, thus highlighting scaffold-induced commitment without exogenous chemicals or cellular reprogramming. Aligned polymer fiber scaffolds which provide instructive cues for RSC differentiation might lead to new biomimetic systems for renal stem cell engineering.

Ultrasoft, flexible nanoelectronics enables electrical monitoring and chemical alteration of the behaviour of stem-cell-derived cardiomyocytes.

The time is right for to highlight the importance of (bio)materials for 3D cell biology. Materials used in 3D cell biology are crucial for both in vitro and in vivo applications in diverse research fields such as tissue engineering and in vitro organ/tissue models development. More than ever, cell biology is benefitting from developments in materials science and related technologies to advance our basic understanding of cell biology and given rise to novel solutions for problems in diagnostics and therapeutics.

Donata Iandolo and Goncalo Silva on the need for an open discussion on mental health in academia.

A novel patterning technique of conductive polymers produced by vapor phase polymerization is demonstrated. The method involves exposing an oxidant film to UV light which changes the local chemical environment of the oxidant and subsequently the polymerization kinetics. This procedure is used to control the conductivity in the conjugated polymer poly(3,4-ethylenedioxythiophene): tosylate by more than six orders of magnitude in addition to producing high-resolution patterns and optical gradients. The mechanism behind the modulation in the polymerization kinetics by UV light irradiation as well as the properties of the resulting polymer are investigated. Funding Agencies|Knut and Alice Wallenberg Foundation [KAW 2011.0050, KAW 2014.0041, KAW 2012.0302]

Bones have been shown to exhibit piezoelectric properties, generating electrical potential upon mechanical deformation and responding to electrical stimulation with the generation of mechanical stress. Thus, the effects of electrical stimulation on bone tissue engineering have been extensively studied. However, in bone regeneration applications, only few studies have focused on the use of electroactive 3D biodegradable scaffolds at the interphase with stem cells. Here a method is described to combine the bone regeneration capabilities of 3D-printed macroporous medical grade polycaprolactone (PCL) scaffolds with the electrical and electrochemical capabilities of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). PCL scaffolds have been highly effective in vivo as bone regeneration grafts, and PEDOT is a leading material in the field of organic bioelectronics, due to its stability, conformability, and biocompatibility. A protocol is reported for scaffolds functionalization with PEDOT, using vapor-phase polymerization, resulting in a conformal conducting layer. Scaffolds' porosity and mechanical stability, important for in vivo bone regeneration applications, are retained. Human fetal mesenchymal stem cells proliferation is assessed on the functionalized scaffolds, showing the cytocompatibility of the polymeric coating. Altogether, these results show the feasibility of the proposed approach to obtain electroactive scaffolds for electrical stimulation of stem cells for regenerative medicine. Funding agencies: Knut and Alice Wallenberg Foundation [KAW 2012.0302]; Nanyang Technological University

This work reports the design of a live-cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue-like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co-culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.

Low temperature aqueous chemical synthesis (LT-ACS) of zinc oxide (ZnO) nanorods (NRs) has been attracting considerable research interest due to its great potential in the development of light-emit ...