Double-Framed Thin Elastomer Devices

Elastomers and, in particular, polydimethylsiloxane (PDMS) are widely adopted as biocompatible mechanically compliant substrates for soft and flexible micro-nanosystems in medicine, biology, and engineering. However, several applications require such low thicknesses (e.g., <100 μm) that make peeling-off critical because very thin elastomers become delicate and tend to exhibit strong adhesion with carriers. Moreover, microfabrication techniques such as photolithography use solvents which swell PDMS, introducing complexity and possible contamination, thus limiting industrial scalability and preventing many biomedical applications. Here, we combine low-adhesion and rectangular carrier substrates, adhesive Kapton frames, micromilling-defined shadow masks, and adhesive-neutralizing paper frames for enabling fast, easy, green, contaminant-free, and scalable manufacturing of thin elastomer devices, with both simplified peeling and handling. The accurate alignment between the frame and shadow masks can be further facilitated by micromilled marking lines on the back side of the low-adhesion carrier. As a proof of concept, we show epidermal sensors on a 50 μm-thick PDMS substrate for measuring strain, the skin bioimpedance and the heart rate. The proposed approach paves the way to a straightforward, green, and scalable fabrication of contaminant-free thin devices on elastomers for a wide variety of applications.Elastomers and, in particular, polydimethylsiloxane (PDMS) are widely adopted as biocompatible mechanically compliant substrates for soft and flexible micro-nanosystems in medicine, biology, and engineering. However, several applications require such low thicknesses (e.g., <100 μm) that make peeling-off critical because very thin elastomers become delicate and tend to exhibit strong adhesion with carriers. Moreover, microfabrication techniques such as photolithography use solvents which swell PDMS, introducing complexity and possible contamination, thus limiting industrial scalability and preventing many biomedical applications. Here, we combine low-adhesion and rectangular carrier substrates, adhesive Kapton frames, micromilling-defined shadow masks, and adhesive-neutralizing paper frames for enabling fast, easy, green, contaminant-free, and scalable manufacturing of thin elastomer devices, with both simplified peeling and handling. The accurate alignment between the frame and shadow masks can be further facilitated by micromilled marking lines on the back side of the low-adhesion carrier. As a proof of concept, we show epidermal sensors on a 50 μm-thick PDMS substrate for measuring strain, the skin bioimpedance and the heart rate. The proposed approach paves the way to a straightforward, green, and scalable fabrication of contaminant-free thin devices on elastomers for a wide variety of applications

Design of biodegradable bi-compartmental microneedles for the stabilization and the controlled release of the labile molecule collagenase for skin healthcare.

Polymeric microneedles (MNs) have emerged as a novel class of drug delivery system thanks to their ability in penetrating the skin with no pain, encapsulate active proteins and in particular, proposed bicompartimental MNs can tune protein release

Mitostatin Is Down-Regulated in Human Prostate Cancer and Suppresses the Invasive Phenotype of Prostate Cancer Cells

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression

Prolonged activity of a recombinant manganese superoxide dismutase through a formulation of polymeric multi-layer nanoassemblies targeting cancer cells

A new isoform of human manganese superoxide dismutase (SOD) has been recently isolated and obtained in a synthetic recombinant form and termed rMnSOD. As compared to other SODs, this isoform exhibits a dramatically improved cellular uptake and an intense antioxidant and antitumoral activity. Unfortunately, its use is severely hampered as this active pharmaceutical ingredient (API) in solution suffers from remarkable instability, which realizes as an interplay of unfolding and aggregation phenomena. This leads the API to be ineffective after three weeks only when stored at 4°C

Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27(kip1), and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis. RESULTS: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases. CONCLUSIONS: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/-) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/- mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers

Biodegradable Nanocapsules produced via Layer-by-Layer Technique on Oil based Templates

In this work we focused the attention on the development of nanocapsules like carriers for their capability to embed high payloads of active substances. Moreover we just used natural materials like vegetal oils and natural polysaccharides to avoid side effects from the use of such nanocarriers. In particular, we chose to start from an oil core template for the preparation of nanocarriers to be used in bio-nano-technology fields. Indeed, oil in water emulsions can easily reach sizes down to 100nm making these systems very interesting from a nanotechnology point of view. Then, there is strong need to load and vehicle lipophilic active substances and drugs in order to face their scarce solubility in water which typically prevents an effective bio-distribution of such molecules. Moreover, it is possible to use vegetal oils and natural surfactants like the soybean and the Lipoid E80 used in this work. Typically, the widespread use of oil carriers in the above said fields is generally limited or prevented by the intrinsic instability of immiscible systems like an emulsion. Herein we have been able to stabilize oil in water emulsions of controlled sizes from 200 to down to 70 nm by decorating them with a biodegradable polymer and by implementing a new multi-dispersion processing. Both emulsions preparation and polymer coated emulsion re-dispersion were carried out by using a high pressure homogenizer at 2000 and around 700bar respectively. Stabilities tunable from few weeks to more than one year were obtained depending on polymer concentration. The higher the polymer concentration is, the higher the stability. These stabilized emulsions already interesting by their own for a wide range of applications were also proved to be suitable templates for the built up of more complex systems like multi-layer based nanocapsules. In particular it was demonstrated the capability to prepare monodisperse biodegradable polymer multi-layer by using the layer by layer technique both on low term stability emulsions and on long term stability emulsions. To make possible the deposition on latter emulsions it was developed a novel method of purification which is mediated by the use of magnetic nano-beads magnetically separated after picking up the excess of polymer in solution. These biodegradable polymer nanocapsules can have a huge impact on the development of new carriers for cancer treatment for a series of advantages such as high payload of lipophilic drugs, possibility to easily functionalize them for active targeting, long circulation in the blood, penetration capability, embed tracers for imaging and so on. Moreover, looking at the possible use of these nanocapsules as carriers to be injected in the blood, polymers have been successfully modified in order to be cross-linked once coupled in the multilayer to provide stability against the oxidizing environment in the blood itself. Finally it was proved capability to use such stabilized template to build a silica layer as outer shell. This is a very interesting bio-interface recognized for its biocompatibility, capability to be functionalized as well as the previous polymeric capsules for a possible use in theranostics. One important aspect emerged in this work is that by assessing the capability to use nano-emulsions stable over time for times comparable to the stable inorganic templates we are opening a fascinating scenario in the templating synthesis. Indeed oil template does not need to be removed, which is risky for the capsule, especially in the case of small sizes and natural polymers, and time consuming; capsules can be pre-loaded with high payloads of scarcely or no soluble bio-molecules, drugs, tracers and so on

ELECTROCATALYTIC POLYMER-BASED POWDER, METHOD OF PRODUCTION AND USE THEREOF

An electrocatalytic polymer-based powder has particles of at least one electronically conductive polymer species in which partlcles are dIsperéed of at least one catalytic redox species 1n which the partlcles of the polymer species and of the catalytic species are of nanometric dimension