Strategies to optimise angiogenesis in synthetic dermal equivalents using in-vitro models

Large burns necessitate skin cover. Skin grafts provide a simple solution but are limited in availability. Cultured keratinocytes provide epidermal cover but invariably fail unless grafted on dermis. Synthetic Dermal Equivalents (SDEs) are mostly collagen based and are dogged by poor take. This thesis concentrates on enhancing the angiogenic capability of SDEs to increase take. Aims To develop components for a "smart" pro-angiogenic matrix for reliable take. To explore and investigate clinical adjuncts, to increase graft angiogenesis. To evaluate angiogenic factors and extracellular matrix components for endothelial cell migration promotion to include in a potential skin equivalent. To explore the in-vitro angiogenic properties of SDEs and the role/effective regimes of Ultrasound and Topical Negative Pressure (TNP). Greatest growth factor stimulation was from TGFB. Influence of migration by angiogenic factors was minimal compared to fibrin. Basal invasion into collagen was low. Fibrin stimulated migration seven fold over that of collagen (pO.OT ANOVA). Fibrin subunits had equal effect to fibrin. Glycosaminoglycans, Fibronectin and Vitronectin addition increased migration over that of collagen. The addition of collagen to fibrin inhibited invasion. Ultrasound at an optimum energy of 0.8W/cm gave a 3 fold increase in migration over control conditions. This was equal to the addition of fibrin. Angiogenesis induced by TNP was optimum in Integra using an intermittent regime. This thesis has shown that collagen, the principal component of all SDEs fails to provide an optimal matrix for invasion of endothelial cells. We have found that the most favourable matrix constituents for endothelial cell migration are fibrin and fibrinogen with fibrin exerting a sevenfold increase in endothelial cell migration over collagen. It has also shown that TNP provides equal endothelial cell ingress to both US and fibrin, only when used intermittently with Integra

Safety surveillance and the estimation of risk in select populations: Flexible methods to control for confounding while targeting marginal comparisons via standardization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152565/1/sim8410_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152565/2/sim8410.pd

Al-, Ga-, and In-doped ZnO thin films via aerosol assisted CVD for use as transparent conducting oxides

Al-, Ga-, and In-doped ZnO thin films were deposited on glass substrates by aerosol assisted chemical vapour deposition (AACVD) at a deposition temperature of 450 °C. The air-stable compound zinc acetylacetonate [Zn(acac)2] was used as a Zn source, whilst for the dopants of Al, Ga and In, the corresponding trichloride was used. Methanol solutions of the metal salts were used as precursor solutions and N2 carrier gas was used for the aerosol. Films were grown in approximately 30 min and were synthesised using dopant values of 5, 10, 15 and 20 mol.% (with respect to the Zn) in the precursor solution. XRD analysis showed that the films were wurtzite ZnO. XPS analysis confirmed the presence of the dopants in the films. Several of the films showed high transparency (>80%) in the visible range, and low resistivity (∼10−3 Ω cm)

Scaling aerosol assisted chemical vapour deposition: Exploring the relationship between growth rate and film properties

Thin films of fluorine doped tin oxide were deposited, by an aerosol assisted chemical vapour deposition route, to study the effect of scaling the growth rate. The effect of precursor concentration on the growth rate of the films and the properties of deposited films were compared. The films were characterised by X-ray diffraction, scanning electron microscopy, UV/vis spectroscopy, X-ray photoelectron spectroscopy and Hall effect measurements. A maximum film growth rate of ca. 100 nm min− 1 was observed, which is significantly faster than previously reported aerosol assisted studies. This method shows the ability of aerosol assisted methods to deliver high growth rates whilst maintaining the ease of doping and control over stoichiometry

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Monitoring Home-Based Activity of Stroke Patients: A Digital Solution for Visuo-Spatial Neglect Evaluation

The possibility to prescribe home-based rehabilitation activity after stroke strongly increases the amount of exercises to perform, thus helping the maintenance of relearned skills, the completion of the rehabilitation program, the practice of physical and mental concentration. Even more important is the monitoring of the patient activity at home, as it is provided by the Remote Monitoring Validation Engineering System (ReMoVES) platform [1]. The present work refers to the implementation and integration in ReMoVES platform of a digital and web-based version of Albert\u2019s [2] and Line Bisection [3] tests devoted to visuo-spatial neglect evaluation and its remote monitoring. A statistical analysis devoted to validating test-retest reliability is proposed. Concurrent correlation between digital and traditional administration of the tests is presented, in order to evaluate the validity of the remote monitoring of the home-administration through ReMoVES platform

Is the biology of breast cancer changing? A study of hormone receptor status 1984-1986 and 1996-1997

Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival

Capturing differences in dental training using a virtual reality simulator

Virtual reality simulators are becoming increasingly popular in dental schools across the world. But to what extent do these systems reflect actual dental ability? Addressing this question of construct validity is a fundamental step that is necessary before these systems can be fully integrated into a dental school's curriculum. In this study, we examined the sensitivity of the Simodont (a haptic virtual reality dental simulator) to differences in dental training experience. Two hundred and eighty-nine participants, with 1 (n = 92), 3 (n = 79), 4 (n = 57) and 5 (n = 61) years of dental training, performed a series of tasks upon their first exposure to the simulator. We found statistically significant differences between novice (Year 1) and experienced dental trainees (operationalised as 3 or more years of training), but no differences between performance of experienced trainees with varying levels of experience. This work represents a crucial first step in understanding the value of haptic virtual reality simulators in dental education

Mechanical properties of sandwich panels constructed from polystyrene/cement mixed cores and thin cement sheet facings

© 2015, © The Author(s) 2015. Sandwich panels are made of two materials that are relatively weak in their separated state, but are improved when they are constructed together in a sandwich panel. Sandwich panels can be used for almost any section of a building including roofs, walls and floors. These building components are regularly required to provide insulation properties, weatherproofing properties and durability in addition to providing structural load bearing characteristics. Polystyrene/cement mixed cores and thin cement sheet facings sandwich panels are Australian products made of cement-polystyrene beaded mixture encapsulated between two thick cement board sheets. The structural properties of sandwich panels constructed of polystyrene/cement cores and thin cement sheet facings are relatively unknown. Therefore, in this study, to understand the mechanical behaviour and properties of those sandwich panels, a series of experimental tests have been performed and the outcomes have been explained and discussed. Based on the results of this study, values for modulus of elasticity and ultimate strength of the sandwich panels in dry and saturated conditions have been determined and proposed for practical applications

Transparent conducting oxide thin films of Si-doped ZnO prepared by aerosol assisted CVD

For the first time, aerosol assisted chemical vapour deposition (AACVD) was used to deposit Si-doped ZnO thin films on glass. Depositions were done at a temperature of 450 °C. The precursor solution was made by dissolving the air-stable compounds zinc acetylacetonate and tetraethyl orthosilicate in methanol with a small addition of acetic acid to aid solubility. The dopant concentration in the precursor solution was optimised to find the best optoelectronic properties. The incorporation of Si into the ZnO lattice was confirmed by unit cell volumes calculated from X-ray diffraction (XRD) data and by X-ray photoelectron spectroscopy (XPS). The films consisted of pure phase wurtzite ZnO, with preferred orientation in the (002) plane. Scanning electron microscopy (SEM) was used to examine the surface morphology of the films. The optical properties of the films were analysed using UV/vis spectroscopy and indicated that the average transmittance in the visible part of the spectrum (400-700 nm) varied between 72% and 80%. The electrical properties of the films were obtained from Hall effect measurements using the van der Pauw method. The incorporation of Si into the films resulted in a decrease in resistivity down to a minimum value of 2.0 × 10−2 Ω cm for the film deposited from a 4 mol% Si : Zn ratio in the precursor solution. This conductive film was a significant improvement over the non-conductive undoped ZnO film