Sequential Infiltration Synthesis of Al2O3 in PMMA Thin Films: Temperature Investigation by Operando Spectroscopic Ellipsometry.

Sequential infiltration synthesis (SIS) is a scalable and valuable technique for the synthesis of organic-inorganic materials with several potential applications at the industrial level. Despite the increasing interest for this technique, a clear picture of the fundamental physicochemical phenomena governing the SIS process is still missing. In this work, infiltration of Al2O3 into thin poly(methyl methacrylate) (PMMA) films using trimethyl aluminum (TMA) and H2O as precursors is investigated by operando dynamic spectroscopic ellipsometry (SE) analysis. The TMA diffusion coefficient values at temperatures ranging from 70 to 100 °C are determined, and the activation energy for the TMA diffusion process in PMMA is found to be Ea = 2.51 ± 0.03 eV. Additionally, systematic data about reactivity of TMA molecules with the PMMA matrix as a function of temperature are obtained. These results provide important information, paving the way to the development of a comprehensive theory for the modeling of the SIS process.

Structured wound angiogenesis instructs mesenchymal barrier compartments in the regenerating nerve.

Organ injury stimulates the formation of new capillaries to restore blood supply raising questions about the potential contribution of neoangiogenic vessel architecture to the healing process. Using single-cell mapping, we resolved the properties of endothelial cells that organize a polarized scaffold at the repair site of lesioned peripheral nerves. Transient reactivation of an embryonic guidance program is required to orient neovessels across the wound. Manipulation of this structured angiogenic response through genetic and pharmacological targeting of Plexin-D1/VEGF pathways within an early window of repair has long-term impact on configuration of the nerve stroma. Neovessels direct nerve-resident mesenchymal cells to mold a provisionary fibrotic scar by assembling an orderly system of stable barrier compartments that channel regenerating nerve fibers and shield them from the persistently leaky vasculature. Thus, guided and balanced repair angiogenesis enables the construction of a "bridge" microenvironment conducive for axon regrowth and homeostasis of the regenerated tissue.

Sequential Infiltration Synthesis of Al2O3 in Biodegradable Polybutylene Succinate: Characterization of the Infiltration Mechanism.

The introduction of inorganic materials into biopolymers has been envisioned as a viable option to modify the optical and structural properties of these polymers and promote their exploitation in different application fields. In this work, the growth of Al2O3 in freestanding ∼30-µm-thick poly(butylene succinate) (PBS) films by sequential infiltration (SIS) at 70 °C via trimethylaluminum (TMA) and H2O precursors was investigated for the first time. The incorporation of Al2O3 into the PBS matrix was clearly demonstrated by XPS analysis and SEM-EDX cross-sectional images showing a homogeneous Al2O3 distribution inside the PBS films. Raman measurements on infiltrated freestanding PBS show a reduction of the signal related to the ester carbonyl group as compared to pristine freestanding PBS films. Accordingly, FTIR and NMR characterization highlighted that the ester group is involved in polymer-precursor interaction, leading to the formation of an aliphatic group and the concomitant rupture of the main polymeric chain. Al2O3 mass uptake as a function of the number of SIS cycles was studied by infiltration in thin PBS films spin-coated on Si substrates ranging from 30 to 70 nm. Mass uptake in the PBS films was found to be much higher than in standard poly(methyl methacrylate) (PMMA) films, under the same process conditions. Considering that the density of reactive sites in the two polymers is roughly the same, the observed difference in Al2O3 mass uptake is explained based on the different free volume of these polymers and the specific reaction mechanism proposed for PBS. These results assessed the possibility to use SIS as a tool for the growth of metal oxides into biopolymers, paving the way to the synthesis of organic-inorganic hybrid materials with tailored characteristics.

Al2O3 Dot and Antidot Array Synthesis in Hexagonally Packed Poly(styrene-block-methyl methacrylate) Nanometer-Thick Films for Nanostructure Fabrication.

Nanostructured organic templates originating from self-assembled block copolymers (BCPs) can be converted into inorganic nanostructures by sequential infiltration synthesis (SIS). This capability is particularly relevant within the framework of advanced lithographic applications because of the exploitation of the BCP-based nanostructures as hard masks. In this work, Al2O3 dot and antidot arrays were synthesized by sequential infiltration of trimethylaluminum and water precursors into perpendicularly oriented cylinder-forming poly(styrene-block-methyl methacrylate) (PS-b-PMMA) BCP thin films. The mechanism governing the effective incorporation of Al2O3 into the PMMA component of the BCP thin films was investigated evaluating the evolution of the lateral and vertical dimensions of Al2O3 dot and antidot arrays as a function of the SIS cycle number. The not-reactive PS component and the PS/PMMA interface in self-assembled PS-b-PMMA thin films result in additional paths for diffusion and supplementary surfaces for sorption of precursor molecules, respectively. Thus, the mass uptake of Al2O3 into the PMMA block of self-assembled PS-b-PMMA thin films is higher than that in pure PMMA thin films.

Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity.

The nervous system requires metabolites and oxygen supplied by the neurovascular network, but this necessitates close apposition of neurons and endothelial cells. We find motor neurons attract vessels with long-range VEGF signaling, but endothelial cells in the axonal pathway are an obstacle for establishing connections with muscles. It is unclear how this paradoxical interference from heterotypic neurovascular contacts is averted. Through a mouse mutagenesis screen, we show that Plexin-D1 receptor is required in endothelial cells for development of neuromuscular connectivity. Motor neurons release Sema3C to elicit short-range repulsion via Plexin-D1, thus displacing endothelial cells that obstruct axon growth. When this signaling pathway is disrupted, epaxial motor neurons are blocked from reaching their muscle targets and concomitantly vascular patterning in the spinal cord is altered. Thus, an integrative system of opposing push-pull cues ensures detrimental axon-endothelial encounters are avoided while enabling vascularization within the nervous system and along peripheral nerves.

Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development.

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development.

The role of antenatal education for the prevention of excessive weight gain during pregnancy.

BACKGROUND: Excessive weight gain (EWG) during pregnancy is associated to adverse maternal-fetal outcomes. The aim of this study was to analyze the situation in a single high intensity care center in Eastern Piedmont, north of Italy. METHODS: This is a cohort study including 715 patients classified into four classes corresponding to pregestational BMI values. Based on the WHO's weight gain for each class, women were subdivided into three groups: inadequate, adequate and excessive increase. RESULTS: EWG was significant in overweight (43.9%) and obese women (37.3%). There was a significant correlation with gestational diabetes (P=0.046), hypertension (P=0.0001), preterm birth (P=0.047), intake of antihypertensive drugs (P=0.0001), maternal study degree (P=0.005), profession (P=0.015), civil status (P=0.003), parity (P=0.039) and paternal ethnicity (P=0.027). Participation at antenatal education for childbirth (AEC) had a positive impact leading to an appropriate weight gain (P=0.004). CONCLUSIONS: If adequately counselled, women understand the consequences of excessive weight gain during pregnancy, comply more to therapy and modify their lifestyle.

Sox2 Acts in Thalamic Neurons to Control the Development of Retina-Thalamus-Cortex Connectivity.

Visual system development involves the formation of neuronal projections connecting the retina to the thalamic dorso-lateral geniculate nucleus (dLGN) and the thalamus to the visual cerebral cortex. Patients carrying mutations in the SOX2 transcription factor gene present severe visual defects, thought to be linked to SOX2 functions in the retina. We show that Sox2 is strongly expressed in mouse postmitotic thalamic projection neurons. Cre-mediated deletion of Sox2 in these neurons causes reduction of the dLGN, abnormal distribution of retino-thalamic and thalamo-cortical projections, and secondary defects in cortical patterning. Reduced expression, in mutants, of Sox2 target genes encoding ephrin-A5 and the serotonin transport molecules SERT and vMAT2 (important for establishment of thalamic connectivity) likely provides a molecular contribution to these defects. These findings unveil thalamic SOX2 function as a novel regulator of visual system development and a plausible additional cause of brain-linked genetic blindness in humans.