Comparison of extraction sites versus artificial defects with xenogenic bone substitute in minipigs

Objectives The preclinical evaluation of bone substitutes is frequently performed in artificially created defects. However, such defects do not reflect the predominant clinical application of bone substitutes for socket preservation. Hence, the goal of this animal study was to compare the performance of a xenogenic bone substitute in extraction sites versus artificial defects. Material and Methods Four study sites each were created in the mandibles of four minipigs in the region of the third premolars and first molars, respectively. On one side, fresh extraction sockets were established while contralaterally trephine defects were created in healed alveolar bone. All sites were augmented using a particulate xenogenic bone substitute, covered by resorbable membranes and allowed to heal for 12 weeks. The amounts of new bone, non-bone tissue and remaining bone substitute granules were quantified through histological and micro-CT analysis. Comparative statistics were based on t-tests for two samples and ANOVA with the level of significance set at α = 0.05. Results Histomorphometric data from only two animals could be quantitatively analyzed due to difficulty with identifying the surgical sites. The percentage of newly formed bone ranged between 53.2% ± 5.6% for artificial defects and 54.9% ± 12.4% for extraction sites. With the exception of ANOVA indicating a greater amount of non-bone tissue in extraction sites as compared to artificial sites (p = 0.047), no statistically significant differences were observed. Micro-CT scans showed patterns similar to the ones observed in histomorphometry. As extraction sites could be identified only in two micro-CT reconstructions, quantitative assessment was not undertaken. Conclusions Despite the comparable performance of bone substitute material in artificial defects and extraction sites found here, the data gathered with this experiment was insufficient for showing equivalence of both approaches

Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation

With the aim of producing β cells for replacement therapies to treat diabetes, several protocols have been developed to differentiate human pluripotent stem cells to β cells via pancreatic progenitors. While in vivo pancreatic progenitors expand throughout development, the in vitro protocols have been designed to make these cells progress as fast as possible to β cells. Here, we report on a protocol enabling a long-term expansion of human pancreatic progenitors in a defined medium on fibronectin, in the absence of feeder layers. Moreover, through a screening of a polymer library we identify a polymer that can replace fibronectin. Our experiments, comparing expanded progenitors to directly differentiated progenitors, show that the expanded progenitors differentiate more efficiently into glucose-responsive β cells and produce fewer glucagon-expressing cells. The ability to expand progenitors under defined conditions and cryopreserve them will provide flexibility in research and therapeutic production

Analisi fluidodinamica del profilo alare Clark-y ed ottimizzazione tramite algoritmo genetico multi-obbiettivo

L’ obbiettivo di questa tesi è quello di ottimizzare in termini di efficienza il profilo aerodinamico dell’ ala del CarboKite della KiteGen tramite l’ algoritmo genetico multi-obbiettivo di MATLAB student. Per conseguire l’ obbiettivo prefissato è stata creata una griglia di calcolo strutturata a celle rettangolari ( C-Mesh ) per la geometria del profilo Clark-y tramite Gambit 2.4.6ope

2D and 3D applications of polymeric biomaterials

The field of biomaterials has seen huge development over the past decade with enormous efforts invested in discovering materials with improved biocompatibility, application and versatility. Polymers can display many properties that make them ideal biomaterials, such as their potential flexibility, low weight, low cost and biodegradability. Moreover, they can be prepared in a wide variety of compositions and forms and be readily fabricated into various shapes and structures. Polymer microarrays represent an efficient high-throughput platform for the screening and discovery of new materials compared to conventional assays with advantages such as high-density screening, internal consistency of assays and the requirement for only small quantities of material. The first part of this thesis describes work in the area of diabetes research with a focus on how dysfunctional β-cells could be replaced by the transplantation of β-cells obtained from pluripotent stem cells. To achieve this aim, high numbers of β-cells are required. A polymer microarray screening approach was used to identify a number of polymers that promoted the attachment of pancreatic progenitor cells and enhanced cell proliferation. Multiple scale-up fabrication techniques were assessed to establish the most suitable approach and surface for long term cell culture leading to the obtainment of reproducible in situ polymerised polymer layers with enhanced binding properties toward pancreatic progenitor cells. These surfaces have the potential to support cell adhesion and proliferation and could find potential use in the industrial sector to increase the production of pancreatic progenitor cells in vitro. In the second part, efforts were made to gain a better understanding of the maturation of β-cells and their behaviour, with the development of 3D hydrogels based on the previously identified polymers. In this scenario, parameters such as stiffness and porosity were evaluated to identify the best environmental conditions to support 3D cell culturing of pancreatic progenitor cells. Several approaches were tested to generate scaffolds with suitable stiffness and porosity leading to the obtainment of scaffolds based on the previously identified polymer composition and with controlled porosity and stiffness. These scaffolds could represent a suitable environment to allow a better understanding of cell organisation and regulation. In a third avenue of work, arrays of 3D biocompatible materials, which were tailored for varying elasticity, hardness, and porosity (to provide the necessary physical cues to control cellular functions) were fabricated. In this chapter, details of the development of an array of eighty 3D double-network hydrogel features are reported. The array features can be produced as single or double networks and modulated in terms of stiffness, viscoelasticity and porosity to assess cell response to materials with a wide range of properties. The final part of the thesis describes the development and screening of polymeric materials to allow a better understanding of cell–surface interactions with various cell types. To investigate the correlation between cell attachment and the nature of the polymer, a series of random and block copolymers were synthesised and examined for their abilities to attach and support the growth of human cervical cancer cells (HeLa) and human embryonic kidney cells (HEK293T), with attachment modelled on monomer ratios, arrangement, and polymer chain length. The results of this screening showed differences between block copolymers and random copolymers in cell adhesion and provide interesting insight into the improvement of polymer coatings for cell culture

Analisi fluidodinamica del profilo alare Clark-y ed ottimizzazione tramite algoritmo genetico multi-obbiettivo

L’ obbiettivo di questa tesi è quello di ottimizzare in termini di efficienza il profilo aerodinamico dell’ ala del CarboKite della KiteGen tramite l’ algoritmo genetico multi-obbiettivo di MATLAB student. Per conseguire l’ obbiettivo prefissato è stata creata una griglia di calcolo strutturata a celle rettangolari ( C-Mesh ) per la geometria del profilo Clark-y tramite Gambit 2.4.

Investigation on the mechanical properties and formability of Ti3Al2.5V tubes deformed at elevated temperatures

Titanium and titanium alloys are largely used in aircrafts to manufacture piping and structural components, thanks to the high strength-to-weight ratio and the excellent corrosion resistance. However, despite the advantages in terms of mechanical and chemical performances, they present significant limits when shaped at room temperature due to the high strength and the low ductility. The use of temperature-assisted processes might represent an interesting option to overcome the above-mentioned limitations, although the effects on the microstructural and chemical properties should be accurately considered. The paper presents the results of investigations on the Ti3Al2.5V alloy, carried out to evaluate the influence that the thermal-cycle parameters have on the mechanical properties and microstructural characteristics of tubes draw bent at elevated temperatures. Tensile tests at elevated temperatures have been performed on specimens directly cut from tubes in order to get the flow-stress curves and elastic material properties. With reference to typical industrial process conditions, different heating rates and soaking times were tested to analyse the influence on the microstructure, namely the grain size, the precipitation of secondary phases and superficial oxidation. Scanning Electron Microscopy and micro-hardness measurement techniques were used to assess the the post-forming characteristics at different temperature and strain rate conditions

Evaluation of anodized surfaces designed for improved soft tissue integration

A rapid and stable integration of dental implant systems into a given tissue is achieved by enabling optimal migration, adhesion, proliferation and differentiation of surrounding cells at the implant and abutment surfaces. The design of abutments requires the careful evaluation and optimization of their surface to provide a strong attachment for the connective tissue and epithelium. In this work the effect of surface anodization on soft tissue integration was evaluated by comparing anodized (Xeal™) and machined surface titanium discs as culture substrates for human gingival epithelial cells (HGEPp) and primary human gingival fibroblasts (HFIB-G). HFIB-G cells did not show any significant preference between the two surfaces whereas HGEPp cells showed significantly faster growth on the Xeal™ surface