Application of texture analysis methods for the characterization of cultured meat.

Mechanical characterization supposes a key step in the development of cultured meat to help mimicking the sensorial properties of already existing commercial products based on traditional meat. This work presents two well stablished methods that can help studying cultured meat mechanical characteristics: texture profile analysis (double compression test) and rheology. These techniques provide data about the elastic and viscous behaviour of the samples but also values about other texture characteristics such as springiness, cohesiveness, chewiness and resilience. In this work, we present a comparison of cultured meat-based samples with commercial of the shelf common meat products (sausage, turkey and chicken breast). Results show that both Young's and Shear modulus in the cultured meat samples can be compared to commercial products in order to understand its properties. The texture characteristics for the cultured meat studied, show values within the range of commercial products. These results demonstrate the applicability of this methodology for the adjustment of mechanical properties of cultured meat products.

Cytotoxicity of Nucleotide-Stabilized Graphene Dispersions on Osteosarcoma and Healthy Cells: On the Way to Safe Theranostics Agents.

An appealing strategy that overcomes the hydrophobicity of pristine graphene and favors its interaction with biological media is colloidal stabilization in aqueous medium with the support of a biomolecule, such as flavin mononucleotide (FMN), as exfoliating/dispersing agent. However, to establish FMN-stabilized graphene (PG-FMN) as suitable for use in biomedicine, its biocompatibility must be proved by a complete assessment of cytotoxicity at the cellular level. Furthermore, if PG-FMN is to be proposed as a theranostic agent, such a study should include both healthy and tumoral cells and its outcome should reveal the nanomaterial as selectively toxic to the latter. Here, we provide an in-depth comparative in vitro analysis of the response of Saos-2 human sarcoma osteoblasts (model tumor cells) and MC3T3-E1 murine preosteoblasts (undifferentiated healthy cells) upon incubation with different concentrations (10-50 µg mL-1) of PG-FMN dispersions constituted by flakes with different average lateral size (90 and 270 nm). Specifically, the impact of PG-FMN on the viability and cell proliferation, reactive oxygen species (ROS) production, and the cellular incorporation process, cell-cycle progression, and apoptosis has been evaluated. PG-FMN was found to be toxic to both types of cells by increasing ROS production and triggering cell-cycle arrest. The present results constitute a cautionary tale on the need to establish the effect of a nanomaterial not only on tumor cells but also on healthy ones before proposing it as anticancer agent.

Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization.

The preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effects were compared. Pegylated graphene oxide (GO-PEG, 200-500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (PG-FMN, 200-400 nm and 100-200 nm) were administered to macrophages, chosen as cellular model due to their key role in the processing of foreign materials and the regulation of inflammatory responses. The results showed that cellular uptake of GBNs was mainly influenced by their lateral size, while the inflammatory potential depended also on the type of functionalization. PG-FMN nanomaterials (both sizes) triggered significantly higher nitric oxide (NO) release, together with some intracellular metabolic changes, similar to those induced by the prototypical inflammatory stimulus LPS. NMR metabolomics revealed that macrophages incubated with smaller PG-FMN displayed increased levels of succinate, itaconate, phosphocholine and phosphocreatine, together with decreased creatine content. The latter two variations were also detected in cells incubated with larger PG-FMN nanosheets. On the other hand, GO-PEG induced a decrease in the inflammatory metabolite succinate and a few other changes distinct from those seen in LPS-stimulated macrophages. Assessment of TNF-α secretion and macrophage surface markers (CD80 and CD206) further corroborated the low inflammatory potential of GO-PEG. Overall, these findings revealed distinct phenotypic and metabolic responses of macrophages to different GBNs, which inform on their immunomodulatory activity and may contribute to guide their therapeutic applications.

Metabolomic response of osteosarcoma cells to nanographene oxide-mediated hyperthermia.

Nanographene oxide (nGO)-mediated hyperthermia has been increasingly investigated as a localized, minimally invasive anticancer therapeutic approach. Near InfraRed (NIR) light irradiation for inducing hyperthermia is particularly attractive, because biological systems mostly lack chromophores that absorb in this spectral window, facilitating the selective heating and destruction of cells which have internalized the NIR absorbing-nanomaterials. However, little is known about biological effects accompanying nGO-mediated hyperthermia at cellular and molecular levels. In this work, well-characterized pegylated nGO sheets with a hydrodynamic size of 300 nm were incubated with human Saos-2 osteosarcoma cells for 24 h and their internalization verified by flow cytometry and confocal microscopy. No effect on cell viability was observed after nGO uptake by Saos-2 cells. However, a proliferation delay was observed due to the presence of nGO sheets in the cytoplasm. 1H NMR metabolomics was employed to screen for changes in the metabolic profile of cells, as this could help to improve understanding of cellular responses to nanomaterials and provide new endpoint markers of effect. Cells internalizing nGO sheets showed noticeable changes in several metabolites compared to control cells, including decreased levels of several amino acids, taurine and creatine and increased levels of phosphocholine and uridine/adenosine nucleotides. After NIR irradiation, cells showed decreases in glutamate and uridine nucleotides, together with increases in glycerophosphocholine and adenosine monophosphate. Overall, this study has shown that the cellular metabolome sensitively responded to nGO exposure and nGO-mediated hyperthermia and that NMR metabolomics is a powerful tool to investigate treatment responses.

Eco-friendly profile of pegylated nano-graphene oxide at different levels of an aquatic trophic chain.

Nanographene oxide (nGO) has been recently proposed as a new antitumoral therapeutic agent, drug delivery carrier and gene transfection vehicle, among others. Treatment is carried out by hyperthermia induced by infrared irradiation. After treatment, the nanosystems will be inevitably excreted and released to the environment. To understand the potential impacts of pegylated nGO (nGO-PEG), three key species from different trophic levels were used: the green micro-algae Raphidocelis subcapitata (growth inhibition test), the cladocera Daphnia magna (acute and chronic tests), and the fish Danio rerio (fish embryo test). Besides a regular standard procedure to assess toxicity, and considering the mode of action of nGO-PEG in cancer treatment, a simultaneous infrared lamp exposure was carried out for D. magna and D. rerio. Additionally, and taking advantage of the phenotypic transparency of D. magna, nGO-PEG was fluorescently tagged to evaluate the potential uptake of nGO-PEG. The R. subcapitata growth inhibition test showed effects during the first 48 h, recovering till the end of the test (96 h). No acute or chronic effects were observed for D. magna, under standard or infrared light exposures although confocal microscope images showed nGO-PEG uptake. Very small percentages of mortality and abnormalities were observed in D. rerio exposed with and without the infrared lamp. Although low hazard may be expected for nGO-PEG in aquatic ecosystems, further studies with species with different life traits should be accomplished, in order to derive more accurate conclusions.

MC3T3-E1 pre-osteoblast response and differentiation after graphene oxide nanosheet uptake.

Nano-graphene oxide (GO) and its functionalized derivatives have aroused a great interest for drug delivery, tissue engineering and photothermal cancer therapy, but their biocompatibility has not yet been fully assessed. The aim of the present study was to evaluate the proliferation and differentiation of MC3T3-E1 pre-osteoblasts after the uptake of GO nanosheets (c.a. 400nm), functionalized with poly(ethylene glycol-amine) (PEG) and labelled with fluorescein isothiocyanate (FITC). Significant proliferation decrease and apoptosis increase were observed 3days after incorporation of FITC-PEG-GO by MC3T3-E1 cells. However, alterations on healthy pre-osteoblast differentiation into cells exhibiting osteoblast phenotype were not observed, as they showed normal alkaline phosphatase levels and matrix mineralization 12days after nanosheet uptake. The results suggest that 40µg/mL concentrations of these nanosheets would not affect the differentiation of healthy pre-osteoblasts, thus these PEG-GO nanosheets have potential to be used for biomedical applications after their internalization, as the induction of local hyperthermia on bone cancer.

Aqueous Exfoliation of Transition Metal Dichalcogenides Assisted by DNA/RNA Nucleotides: Catalytically Active and Biocompatible Nanosheets Stabilized by Acid-Base Interactions.

The exfoliation and colloidal stabilization of layered transition metal dichalcogenides (TMDs) in an aqueous medium using functional biomolecules as dispersing agents have a number of potential benefits toward the production and practical use of the corresponding two-dimensional materials, but such a strategy has so far remained underexplored. Here, we report that DNA and RNA nucleotides are highly efficient dispersants in the preparation of stable aqueous suspensions of MoS2 and other TMD nanosheets at significant concentrations (up to 5-10 mg mL-1). Unlike the case of common surfactants, for which adsorption on 2D materials is generally based on weak dispersive forces, the exceptional colloidal stability of the TMD flakes was shown to rely on the presence of relatively strong, specific interactions of Lewis acid-base type between the DNA/RNA nucleotide molecules and the flakes. Moreover, the nucleotide-stabilized MoS2 nanosheets were shown to be efficient catalysts in the reduction of nitroarenes (4-nitrophenol and 4-nitroaniline), thus constituting an attractive alternative to the use of expensive heterogeneous catalysts based on noble metals, and exhibited an electrocatalytic activity toward the hydrogen evolution reaction that was not impaired by the possible presence of nucleotide molecules adsorbed on their active sites. The biocompatibility of these materials was also demonstrated on the basis of cell proliferation and viability assays. Overall, the present work opens new vistas on the colloidal stabilization of 2D materials based on specific interactions that could be useful toward different practical applications.

3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine.

The current study reports on the manufacturing by rapid prototyping technique of three-dimensional (3D) scaffolds based on silicon substituted hydroxyapatite with Elastin-like Recombinamers (ELRs) functionalized surfaces. Silicon doped hydroxyapatite (Si-HA), with Ca10(PO4)5.7(SiO4)0.3(OH)1.7h0.3 nominal formula, was surface functionalized with two different types of polymers designed by genetic engineering: ELR-RGD that contain cell attachment specific sequences and ELR-SNA15/RGD with both hydroxyapatite and cells domains that interact with the inorganic phase and with the cells, respectively. These hybrid materials were subjected to in vitro assays in order to clarify if the ELRs coating improved the well-known biocompatible and bone regeneration properties of calcium phosphates materials. The in vitro tests showed that there was a total and homogeneous colonization of the 3D scaffolds by Bone marrow Mesenchymal Stromal Cells (BMSCs). In addition, the BMSCs were viable and able to proliferate and differentiate into osteoblasts. STATEMENT OF SIGNIFICANCE: Bone tissue engineering is an area of increasing interest because its main applications are directly related to the rising life expectancy of the population, which promotes higher rates of several bone pathologies, so innovative strategies are needed for bone tissue regeneration therapies. Here we use the rapid prototyping technology to allow moulding ceramic 3D scaffolds and we use different bio-polymers for the functionalization of their surfaces in order to enhance the biological response. Combining the ceramic material (silicon doped hydroxyapatite, Si-HA) and the Elastin like Recombinamers (ELRs) polymers with the presence of the integrin-mediate adhesion domain alone or in combination with SNA15 peptide that possess high affinity for hydroxyapatite, provided an improved Bone marrow Mesenchymal Stromal Cells (BMSCs) differentiation into osteoblastic linkage.

Optimized graphene oxide foam with enhanced performance and high selectivity for mercury removal from water.

This work explores the preparation of three-dimensional graphene oxide macroscopic structures, shaped by self-assembling single graphene oxide (3DGO) sheets with control of its surface chemistry by combining with nitrogen functional groups (3DGON), or with nitrogen and sulphur functional groups (3DGOSN), and their application in the removal of mercury (Hg(II)) from aqueous solutions. The chemical structure of the materials was assessed by using different characterization techniques: SEM, XPS and BET. Adsorption studies conducted in Hg(II) contaminated ultra-pure water reveal the enhanced ability of 3DGON for the adsorption of this metal, when compared to the other GO foams. A small dose of 3DGON (10 mg L(-1)) allows to remove up to 96% of Hg(II) after 24 h of contact time, leading to a residual concentration in solution close to the guideline value for drinking water (1 µg L(-1)). The ability of this material to adsorb Hg (II) was evaluated relatively to different experimental parameters such as pH, sorbent dose, time and effect on different competing metal ions. Real application was also evaluated by testing its performance in two different natural matrices, river and sea water, with very promising results.

Three-dimensional printed PCL-hydroxyapatite scaffolds filled with CNTs for bone cell growth stimulation.

A three-phase [nanocrystalline hydroxyapatite (HA), carbon nanotubes (CNT), mixed in a polymeric matrix of polycaprolactone (PCL)] composite scaffold produced by 3D printing is presented. The CNT content varied between 0 and 10 wt % in a 50 wt % PCL matrix, with HA being the balance. With the combination of three well-known materials, these scaffolds aimed at bringing together the properties of all into a unique material to be used in tissue engineering as support for cell growth. The 3D printing technique allows producing composite scaffolds having an interconnected network of square pores in the range of 450-700 µm. The 2 wt % CNT scaffold offers the best combination of mechanical behaviour and electrical conductivity. Its compressive strength of ∼4 MPa is compatible with the trabecular bone. The composites show typical hydroxyapatite bioactivity, good cell adhesion and spreading at the scaffolds surface, this combination of properties indicating that the produced 3D, three-phase, scaffolds are promising materials in the field of bone regenerative medicine. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1210-1219, 2016.

Breakdown into nanoscale of graphene oxide: confined hot spot atomic reduction and fragmentation.

Nano-graphene oxide (nano-GO) is a new class of carbon based materials being proposed for biomedical applications due to its small size, intrinsic optical properties, large specific surface area, and easy to functionalize. To fully exploit nano-GO properties, a reproducible method for its production is of utmost importance. Herein we report, the study of the sequential fracture of GO sheets onto nano-GO with controllable lateral width, by a simple, and reproducible method based on a mechanism that we describe as a confined hot spot atomic fragmentation/reduction of GO promoted by ultrasonication. The chemical and structural changes on GO structure during the breakage were monitored by XPS, FTIR, Raman and HRTEM. We found that GO sheets starts breaking from the defects region and in a second phase through the disruption of carbon bonds while still maintaining crystalline carbon domains. The breaking of GO is accompanied by its own reduction, essentially by the elimination of carboxylic and carbonyl functional groups. Photoluminescence and photothermal studies using this nano-GO are also presented highlighting the potential of this nanomaterial as a unique imaging/therapy platform.

Endocytic mechanisms of graphene oxide nanosheets in osteoblasts, hepatocytes and macrophages.

Nano-graphene oxide (GO) has attracted great interest in nanomedicine due to its own intrinsic properties and its possible biomedical applications such as drug delivery, tissue engineering and hyperthermia cancer therapy. However, the toxicity of GO nanosheets is not yet well-known and it is necessary to understand its entry mechanisms into mammalian cells in order to avoid cell damage and human toxicity. In the present study, the cellular uptake of pegylated GO nanosheets of ca. 100 nm labeled with fluorescein isothiocyanate (FITC-PEG-GOs) has been evaluated in the presence of eight inhibitors (colchicine, wortmannin, amiloride, cytochalasin B, cytochalasin D, genistein, phenylarsine oxide and chlorpromazine) that specifically affect different endocytosis mechanisms. Three cell types were chosen for this study: human Saos-2 osteoblasts, human HepG2 hepatocytes and murine RAW-264.7 macrophages. The results show that different mechanisms take part in FITC-PEG-GOs uptake, depending on the characteristics of each cell type. However, macropinocytosis seems to be a general internalization process in the three cell lines analyzed. Besides macropinocytosis, FITC-PEG-GOs can enter through pathways dependent on microtubules in Saos-2 osteoblasts, and through clathrin-dependent mechanisms in HepG2 hepatocytes and RAW-264.7 macrophages. HepG2 cells can also phagocytize FITC-PEG-GOs. These findings help to understand the interactions at the interface of GO nanosheets and mammalian cells and must be considered in further studies focused on their use for biomedical applications.

Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin-glutaraldehyde biopolymer-coated hydroxyapatite.

Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications.

[Rationalizing versus rationing in the practice of clinical nutrition; fourth Jesús Culebras lecture]. / Racionalización versus racionamiento en la práctica de la nutrición clínica; cuarta lección Jesús Culebras.

The current economic situation is the reason for this conference that will be split in two main areas: first, we will focus on general concepts on rationalizing versus rationing in health care, and secondly, on rationing in the practice of clinical nutrition. According to the Spanish Royal Academy of the Language, to rationalize is to organize the production or the work in a manner such the yields are increased or the costs are reduced with the least effort. However, to ration is the action and effect of rationing or limiting the consumption of something to prevent negative consequences. In Europe, the percentage of the Gross National Product dedicated to health care progressively decreases whereas the costs of health care are ever increasing. From the economic viewpoint, this would be the main reason why the health care authorities have no other option but rationing. Until what extent the ethical principle of justice is compatible with rationing? Ethically, it seems that in order to accept rationing, not only a fair distribution of the limited resources should be achieved, but also a rational use of them. If we accept that limiting the health care allowances is necessary, we should then answer some questions: is it ethical not to limit? Who decides what is medically necessary? How is it decided? With no coherent answers to these questions it is ethically difficult to accept rationing from a healthcare viewpoint. When dealing with rationing in the practice of clinical nutrition, we should focus on how rationing impacts on hyponutrition, and more particularly on disease-related hyponutrition, since this is the focus of Clinical Nutrition. Given its importance and its implications, in several countries, including Spain, actions integrated in the European Union strategy "Together for health: a Strategic Approach for the EU 2008-2013", are being performed aimed at taking decisions for preventing and managing hyponutrition. However, restrictions persist with the imperative necessity of using all the tools available to prevent hyponutrition in patients at risk, to early detect malnourished patients or patients at risk for hyponutrition, and to establish the most appropriate actions.

Racionalización versus racionamiento en la práctica de la nutrición clínica; cuarta lección Jesús Culebras / Rationalizing versus rationing in the practice of clinical nutrition; fourth Jesús Culebras lecture

La situación económica actual ha dado pie al tema de esta conferencia que se desarrollará en dos grandes apartados: primero, trataremos de ideas generales sobre la racionalización versus el racionamiento en la sanidad, y, posteriormente, del racionamiento en la práctica de la nutrición clínica. Racionalizar, según la Real Academia Española de la Lengua, es organizar la producción o el trabajo de manera que aumente los rendimientos o reduzca los costos con el mínimo esfuerzo. Mientras que por racionamiento se entiende la acción y efecto de racionar o limitar el consumo de algo para evitar consecuencias negativas. En Europa, el porcentaje del Producto Interior Bruto destinado a Sanidad cae progresivamente mientras el coste de la Sanidad no para de aumentar. Desde el punto de vista económico, éste sería el principal motivo por el que las autoridades sanitarias parece que no tienen más alternativa que racionar. ¿Hasta qué punto el principio ético de justicia es compatible con el racionamiento? Éticamente, parece que para aceptar el racionamiento debería cumplirse no sólo una distribución justa de los recursos limitados sino también el uso racional de los mismos. Si se acepta que el recorte en prestaciones sanitarias es necesario, deberíamos responder a diversas preguntas: ¿qué es lo ético no recortar?, ¿quién decide lo que es médicamente necesario?, ¿cómo se decide? Sin respuestas coherentes a estas preguntas resulta difícil, éticamente, aceptar el racionamiento a nivel sanitario. Al tratar el racionamiento en la práctica de la nutrición clínica, debemos centrarnos en cómo el racionamiento afecta a la desnutrición, y más concretamente de la desnutrición relacionada con la enfermedad, ya que ello centra el origen de la Nutrición Clínica. Por su importancia e implicaciones se están llevando a cabo, en diversos países entre ellos en España, acciones integradas en la estrategia de la Unión Europea: "Together for health: a Strategic Approach for the EU 2008-2013" encaminadas a tomar medidas dirigidas a prevenir y tratar la desnutrición. Pero a pesar de ello, las restricciones persisten, situándonos en la necesidad imperativa de utilizar todas las herramientas a nuestro alcance para prevenir el desarrollo de la desnutrición en los pacientes en riesgo, para detectar precozmente los pacientes con desnutrición o riesgo de desarrollarla y para establecer las medidas de actuación más adecuadas (AU)

The current economic situation is the reason for this conference that will be split in two main areas: first, we will focus on general concepts on rationalizing versus rationing in health care, and secondly, on rationing in the practice of clinical nutrition. According to the Spanish Royal Academy of the Language, to rationalize is to organize the production or the work in a manner such the yields are increased or the costs are reduced with the least effort. However, to ration is the action and effect of rationing or limiting the consumption of something to prevent negative consequences. In Europe, the percentage of the Gross National Product dedicated to health care progressively decreases whereas the costs of health care are ever increasing. From the economic viewpoint, this would be the main reason why the health care authorities have no other option but rationing. Until what extent the ethical principle of justice is compatible with rationing? Ethically, it seems that in order to accept rationing, not only a fair distribution of the limited resources should be achieved, but also a rational use of them. If we accept that limiting the health care allowances is necessary, we should then answer some questions: is it ethical not to limit? Who decides what is medically necessary? How is it decided? With no coherent answers to these questions it is ethically difficult to accept rationing from a healthcare viewpoint. When dealing with rationing in the practice of clinical nutrition, we should focus on how rationing impacts on hyponutrition, and more particularly on disease-related hyponutrition, since this is the focus of Clinical Nutrition. Given its importance and its implications, in several countries, including Spain, actions integrated in the European Union strategy "Together for health: a Strategic Approach for the EU 2008-2013", are being performed aimed at taking decisions for preventing and managing hyponutrition. However, restrictions persist with the imperative necessity of using all the tools available to prevent hyponutrition in patients at risk, to early detect malnourished patients or patients at risk for hyponutrition, and to establish the most appropriate actions (AU)

Comparison of synthetic dopamine-eumelanin formed in the presence of oxygen and Cu2+ cations as oxidants.

Eumelanin is not only a ubiquitous pigment among living organisms with photoprotective and antioxidant functions, but is also the subject of intense interest in materials science due to its photoconductivity and as a possible universal coating platform, known as "polydopamine films". The structure of eumelanin remains largely elusive, relying either on a polymeric model or on a heterogeneous aggregate structure. The structure of eumelanin as well as that of the closely related "polydopamine films" can be modified by playing on the nature of the oxidant used to oxidize dopamine or related compounds. In this investigation, we show that dopamine-eumelanins produced from dopamine in the presence of either air (O2 being the oxidant) or Cu(2+) cations display drastically different optical and colloidal properties in relation with a different supramolecular assembly of the oligomers of 5,6 dihydroxyindole, the final oxidation product of dopamine. The possible origin of these differences is discussed on the basis of Cu(2+) incorporation in Cu dopamine-eumelanin.

Nano-graphene oxide: a potential multifunctional platform for cancer therapy.

Nano-GO is a graphene derivative with a 2D atomic layer of sp² bonded carbon atoms in hexagonal conformation together with sp³ domains with carbon atoms linked to oxygen functional groups. The supremacy of nano-GO resides essentially in its own intrinsic chemical and physical structure, which confers an extraordinary chemical versatility, high aspect ratio and unusual physical properties. The chemical versatility of nano-GO arises from the oxygen functional groups on the carbon structure that make possible its relatively easy functionalization, under mild conditions, with organic molecules or biological structures in covalent or non-covalent linkage. The synergistic effects resulting from the assembly of well-defined structures at nano-GO surface, in addition to its intrinsic optical, mechanical and electronic properties, allow the development of new multifunctional hybrid materials with a high potential in multimodal cancer therapy. Herein, a comprehensive review of the fundamental properties of nano-GO requirements for cancer therapy and the first developments of nano-GO as a platform for this purpose is presented.

The effects of graphene oxide nanosheets localized on F-actin filaments on cell-cycle alterations.

Graphene oxide (GO) is considered to be a promising nanomaterial for biomedical applications due to its small two-dimensional shape besides its electrical and mechanical properties. However, only a few data concerning the cell responses to this material have been described and the GO biocompatibility has not been yet fully assessed. In the present study, graphene oxide nanosheets (GOs) decorated with 1-arm (1-GOs) and 6-arm (6-GOs) poly(ethylene glycol-amine) (PEG) have been incubated with cultured Saos-2 osteoblasts, MC3T3-E1 preosteoblasts and RAW-264.7 macrophages to analyze several key cell markers for in vitro biocompatibility evaluation. The results demonstrate that, after internalization, GO nanosheets are localized on F-actin filaments inducing cell-cycle alterations, apoptosis and oxidative stress in these cell types. The observed GOs effects must be considered in further studies focused on photothermal cancer therapy as a synergistic factor.

Biological performance of hydroxyapatite-biopolymer foams: in vitro cell response.

Uncoated and biopolymer-coated nanocrystalline hydroxyapatite (HA) macroporous foams are presented as promising candidates as scaffolds for bone tissue regeneration. To this end, foam degradability, the cytotoxic effects on osteoblast-like cells of foam degradation by-products and biocompatibility with osteoblast-like cells were assayed on the three-dimensional (3-D) foam surface. The results show that the 3-D interconnected architectural design of these HA foams allows excellent osteoblast internalization, proliferation and differentiation, exhibiting adequate colonization over the entire scaffold surface with an appropriate degradation rate without any cytotoxic effects.