Wearable electronics are attracting increasing attention as recent developments in materials, mechanics, and manufacturing techniques create new opportunities for the integration of high-quality electronic systems into a single miniaturized Continuous monitoring of human physiological signals is critical to managing personal healthcare by early detection of health disorders. Wearable and implantable devices are attracting growing attention as they show great potential for real-time recording of physiological conditions and body motions. Conventional piezoelectric sensors have the advantage of potentially being self-powered, but have limitations due to their intrinsic lack of stretchability. Herein, a kirigami approach to realize a novel stretchable strain sensor is introduced through a network of cut patterns in a piezoelectric thin film, exploiting the anisotropic and local bending that the patterns induce. The resulting pattern simultaneously enhances the electrical performance of the film and its stretchability while retaining the mechanical integrity of the underlying materials. The power output is enhanced from the mechanoelectric piezoelectric sensing effect by introducing an intersegment, through-plane, electrode pattern. By additionally integrating wireless electronics, this sensing network could work in an entirely battery-free mode. The kirigami stretchable piezoelectric sensor is demonstrated in cardiac monitoring and wearable body tracking applications. The integrated soft, stretchable, and biocompatible sensor demonstrates excellent in vitro and ex vivo performances and provides insights for the potential use in myriad biomedical and wearable health monitoring applications.
In developmental biology, gradients of bioactive signals direct the formation of structural transitions in tissue that are key to physiological function. Failure to reproduce these native features in an in vitro setting can severely limit the success of bioengineered tissue constructs. In this report, we introduce a facile and rapid platform that uses magnetic field alignment of glycosylated superparamagnetic iron oxide nanoparticles, pre-loaded with growth factors, to pattern biochemical gradients into a range of biomaterial systems. Gradients of bone morphogenetic protein 2 in agarose hydrogels were used to spatially direct the osteogenesis of human mesenchymal stem cells and generate robust osteochondral tissue constructs exhibiting a clear mineral transition from bone to cartilage. Interestingly, the smooth gradients in growth factor concentration gave rise to biologically-relevant, emergent structural features, including a tidemark transition demarcating mineralized and non-mineralized tissue and an osteochondral interface rich in hypertrophic chondrocytes. This platform technology offers great versatility and provides an exciting new opportunity for overcoming a range of interfacial tissue engineering challenges.
In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.
Despite the rapid ongoing expansion in the use of nanomaterials, we still know little about their biological interaction and biodistribution within the human body. If medically relevant nanoparticles can cross specific cell barriers they may disseminate through the body beyond the original target and may reach particularly sensitive areas such as the foetus. This study utilised an in vitro barrier model of the placenta to explore toxicity, uptake and transport of iron oxide and silica nanoparticles. The findings indicate that these nanoparticles can transfer extensively across the placental barrier model but physico-chemical characteristics such as surface chemistry impact upon both uptake and transport. Iron oxide cytotoxicity was evident at lower doses and shorter exposure compared with silica and may be of clinical relevance. In vivo correlation of in vitro findings is essential but in vitro models may provide worst case-exposure estimates to help reduce the amount of testing required.
BackgroundOrganophosphate pesticides are widely used on food crops grown in the EU. While they have been banned from indoor use in the US for a decade due to adverse health effects, they are still the most prevalent pesticides in the EU, with Chlorpyrifos (CPF) being the most commonly applied. It has been suggested CPF affects neurodevelopment even at levels below toxicity guidelines. Younger individuals may be more susceptible than adults due to biological factors and exposure settings.MethodsA literature review was undertaken to assess the evidence for CPF contributing to neurodevelopmental disorders in infants and children. Other literature was consulted in order to formulate a causal chain diagram showing the origins, uptake, and neurological effects of animal and human exposure to CPF.The causal chain diagram and a questionnaire were distributed online to scientific experts who had published in relevant areas of research. They were asked to assess their confidence levels on whether CPF does in fact contribute to adverse neurodevelopment outcomes and rate their confidence in the scientific evidence. A second questionnaire queried experts as to which kind of policy action they consider justifiable based on current knowledge. In a special workshop session at the EuroTox congress in Dresden in 2009 the results of both questionnaires were further discussed with invited experts, as a basis for a policy brief with main messages for policy makers and stakeholders.ResultsMost experts who responded to the first questionnaire felt that there was already enough evidence to support a ban on indoor uses of CPF in the EU. However, most felt additional research is still required in several areas. The responses from the first questionnaire were used to formulate the second questionnaire addressing the feasibility of government action. In turn, these expert participants were invited to attend a special session at the EuroTox congress in Dresden in 2009.ConclusionsSome of the evidence that CPF contributes to neurodevelopmental disorders is still disputed among experts, and the overall sense is that further research and public awareness are warranted. There have been campaigns in North America making the potential exposure concerns known, but such information is not widely known in the EU. The ability of government action to produce change is strongly felt in some quarters while others believe better knowledge of consumer use trends would have a greater impact.
A better understanding of how properties of NPs define their interactions with cells, tissues and organs in exposed humans is a considerable scientific challenge, but one that must be addressed if there is to be safe and responsible use of biomedical NPs.
Nanogenotoxicity is a crucial endpoint in safety testing of nanomaterials as it addresses potential mutagenicity, which has implications for risks of both genetic disease and carcinogenesis. Within the NanoTEST project, we investigated the genotoxic potential of well-characterised nanoparticles (NPs): titanium dioxide (TiO2) NPs of nominal size 20 nm, iron oxide (8 nm) both uncoated (U-Fe3O4) and oleic acid coated (OC-Fe3O4), rhodamine-labelled amorphous silica 25 (Fl-25 SiO2) and 50 nm (Fl-50 SiO) and polylactic glycolic acid polyethylene oxide polymeric NPs - as well as Endorem® as a negative control for detection of strand breaks and oxidised DNA lesions with the alkaline comet assay. Using primary cells and cell lines derived from blood (human lymphocytes and lymphoblastoid TK6 cells), vascular/central nervous system (human endothelial human cerebral endothelial cells), liver (rat hepatocytes and Kupffer cells), kidney (monkey Cos-1 and human HEK293 cells), lung (human bronchial 16HBE14o cells) and placenta (human BeWo b30), we were interested in which in vitro cell model is sufficient to detect positive (genotoxic) and negative (non-genotoxic) responses. All in vitro studies were harmonized, i.e. NPs from the same batch, and identical dispersion protocols (for TiO2 NPs, two dispersions were used), exposure time, concentration range, culture conditions and time-courses were used. The results from the statistical evaluation show that OC-Fe3O4 and TiO2 NPs are genotoxic in the experimental conditions used. When all NPs were included in the analysis, no differences were seen among cell lines - demonstrating the usefulness of the assay in all cells to identify genotoxic and non-genotoxic NPs. The TK6 cells, human lymphocytes, BeWo b30 and kidney cells seem to be the most reliable for detecting a dose-response.
Until recently, bioprinting was largely limited to highly interdisciplinary research teams, as the process requires significant input from specialists in the fields of materials science, engineering, and cell biology. With the advent of commercially available high‐performance bioprinters, the field has become accessible to a wider range of research groups, who can now buy the hardware off the shelf instead of having to build it from scratch. As a result, bioprinting has rapidly expanded to address a wide array of research foci, which include organotypic in vitro models, complex engineered tissues, and even bioprinted microbial systems. Moreover, in the early days, the range of suitable bioinks was limited. Now, there is a plethora of viable options to suit many cell phenotypes. This rapidly evolving dynamic environment creates endless opportunities for scientists to design and construct highly complex biological systems. However, this scientific diversity presents its own set of challenges, such as defining standardized protocols for characterizing bioprinted structures, which is essential for eventual organ replacement. In this progress report, the current state‐of‐the‐art in the field of bioprinting is discussed, with a special emphasis on recent hardware developments, bioprinting for regenerative medicine, and late‐breaking nontraditional topics.
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