1,721,041 research outputs found
A novel biodegradable poly(ε-caprolactone urea)urethane incorporating polyhedral oligomeric silsesquioxane nanocomposite and applications for skin tissue engineering
Get PDFSkin protects our bodies for a lifetime and extensive loss of this barrier renders the individual susceptible to infections and death. Clinically available treatment options, however, are limited in establishing both functional and cosmetic satisfaction. The work described in this thesis is therefore concerned with the development and characterization of a novel biodegradable nanocomposite system displaying suitable properties as skin tissue engineering scaffolds. A novel family of segmented polyurethanes (PU) with increasing hard segment content based on a poly(ε-caprolactone urea)urethane backbone incorporating POSS nanoparticles was synthesized and analysed in terms of material characteristics and biocompatibility. Incorporation of POSS nanoparticles into the PU backbone yielded mostly amorphous materials as corroborated by distinct glass transitions visible on differential scanning calorimetry spectra. With incrementally increasing hard segment content, ultimate tensile strength increased from ~10 to 21 MPa accompanied by increased values for elastic moduli from 0.03 to 0.06 MPa. Number average molecular weights (Mn) decreased with increasing hard segment content due to a corresponding decrease in the proportion of PCL. Sterilization studies raised fundamental concerns regarding the suitability of conventionally available techniques since hydrolytically and temperature labile polymers are susceptible to degradation. The results obtained suggest 70 % ethanol to be a suitable laboratory-based disinfectant which was further demonstrated to have favourable effects on skin cell compatibility. Degradation studies revealed hard segment-dependent modulation of the degradation rate and the materials’ viscoelasticity. In vivo implantation studies of porous scaffolds demonstrated firm integration with the subcutaneous tissue and extensive vascularization. The results obtained in this work highlight (i) the ability to control scaffold degradation rates and mechanical properties and (ii) cellular as well as in vivo biocompatibility, all of which fundamental in the development of a versatile skin tissue engineering scaffold
A Nano-Inspired Multifunctional POSS-PCU Covered Stent: Endothelial Progenitor Cell Capture with Stealth Liposomal Drug Release
No full textThe 2 main unresolved issues inherent in coronary stents are in-stent restenosis (ISR) and late stent thrombosis (ST). ISR is largely due to vascular smooth muscle cell (VSMC) proliferation, and ST is attributed to a lack of re-endothelialization. This thesis describes the conceptualization and development of a biofunctionalized polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) platform, for the express purpose of circumventing ISR and ST. A bare-metal stent is embedded between 3 layers of POSS-PCU facilitating endothelial progenitor cell (EPC) capture using antibodies, in tandem with sustained drug release using stealth liposomes. The luminal area is impregnated with anti-CD34 antibodies, covalently bonded to a POSS-PCU base platform, for EPC capture to enhance re-endothelialization. Results indicated successful antibody immobilization, with an increased propensity for EPC capture compared to controls. The abluminal area is integrated with paclitaxel-encapsulated stealth liposomes, with an ultrathin layer of POSS-PCU sprayed on top using an ultrasonic atomization spray system, for sustained drug release to inhibit VSMC proliferation. Results in this aspect demonstrated sustained drug release with augmented cell kill in a 28-day in vitro cell culture. Mechanical engineering tests performed on the finished product demonstrated superior mechanical functionality as a covered stent. Various sterilization techniques and a biodegradation model were also employed to robustly assess product viability, with results indicating that EPC capture potential and stealth liposomal drug elution were preserved. Taken together, this novel POSS-PCU covered stent can enhance re-endothelialization and inhibit VSMC proliferation, thereby addressing the issues of ST and ISR respectively. Furthermore, the covering membrane could also serve as a physical barrier against atherosclerotic plaque dislodgement to prevent thromboembolism. It is therefore hoped that the proof-of-principle demonstrated here in this thesis would serve as an impetus for further translational research, with the eventual goal of taking it from bench to bedside
Design and Development of a Synthetic POSS-Nanocomposite Implant for Auricular Reconstruction
No full textAuricular reconstruction using sculpted autologous costal cartilage following congenital microtia, trauma and cancer is effective, but complex, time consuming and may incur donor site morbidity. Current conventional synthetic alternatives are associated with infection and extrusion. A novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane (POSS) covalently bonded to poly(carbonate-urea-urethane) (PCU), has developed and patented in our laboratory and displayed promising clinical applications in first-in-human. POSS-PCU has been utilised to develop synthetic 3D auricle construct for use as auricular cartilage replacement, which aims to reduce extrusion rates by mimicking the mechanical properties of human ears and by encouraging desirable cellular interactions. Methods & Material: A novel custom-made ear-shaped 3D negative glass-mould was fabricated from positive 3D-printing ear model of a CT scan obtained from the external part of the human ear. This glass-mould was used to manufacture 3D auricular scaffolds using POSS-PCU materials. Two novel fabrication techniques solvent-evaporation/porogen-leaching (POSS-PCUs) and phase-separation/porogen-leaching (POSS-PCUc) were developed to produce nanocomposite scaffolds. The fabrication, physicochemical properties (including nanoscale topography) and in-vitro cellular interactions of these novel fabricated nanocomposites were extensively studied and compared to current commercially available synthetic material (Medpor®). Further cell-material interactions were completed on the optimized POSS-PCUs and Medpor® to examine the angiogenic and inflammatory responses to these materials using human fibroblasts and macrophages. Finally, POSS-PCUs scaffolds with two different pore sizes ranging from 50-100µm & 150-250µm were subcutaneously evaluated compared with Medpor® in-vivo in a rodent model for up-to 3 months. Results: The glass-mould design using 3D-printing technology allowed the manufacture of customised auricular POSS-PCU scaffolds that replicated the original human auricle. Two different polymeric fabrication methods resulted in the production of two types of nanocomposite scaffolds with same average pore size (150µm) but different porosity (63.47±1.35% in POSS-PCUs & 85.21±1.19% in POSS-PCUc). POSS-PCUs had similar elastic modulus (5.73±0.17 MPa) to human ear cartilage (5.02±0.17 MPa) compared with POSS-PCUc (0.58±0.12 MPa) and Medpor® (140.9±0.04 MPa) elastic modulus which were significantly different (P<0.001). Optimised POSS-PCUs nanocompoiste showed greater protein adsorption, and subsequently increased fibroblast adhesion, growth, and collagen production in vitro, compared to Medpor®. A higher volume fraction of fibrotic tissue ingrowth with negligible capsular formation was achieved in vivo in POSS-PCUs with pore-sizes of 150-250µm than Medpor®. No evidence of chronic inflammation was observed in the implanted scaffolds. Conclusion: These findings as well as other clinical studies in man suggest that POSS-PCUs nanocomposite can be a promising biomaterial for auricular reconstruction
Development of endovascular stent-grafts based on a nanocomposite polymer
Get PDFObjective: To use a novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane with superior bio-mimetic properties in the development of endovascular stent-grafts. Methods: A self-expanding and sutureless aortic stent-graft was developed using nanocomposite polymer bonded to Nitinol. A new aortic model was designed for physiological assessment of stent-grafts and compliance and viscoelasticity were measured and compared with porcine aortas as control. The stent-grafts (n=4) were fatigue tested using in vitro accelerated model for 400-million cycles equivalent to 10-years in human body and compared with zero-cycled control. A curved and conformable stent-graft was developed for thoracic aorta and aortic arch. Compliance and stiffness index of the thoracic stent-graft were measured in vitro and compared to FDA-approved Gore TagTM stent-graft based on ePTFE (expanded polytetrafluoroethylene). MRI compatibility of the thoracic stent-graft was assessed by analysing signal attenuation and velocity measurements (flux) and compared to FDA-approved Medtronic ValiantTM. Results: The stent-graft had expanded diameter of 31.1 mm and was successfully collapsed to 6.5 mm to achieve delivery profile similar to current devices. The thoracic stent-graft had uniform graft thickness of 150.7±6.6 µg and conformed to the curvature of aortic arch. The new aortic model was significantly more compliant than porcine aortas with no significant difference in elastic stiffness. All the stent-grafts successfully completed accelerated pulsatile fatigue testing. Scanning electron microscopy images confirmed uniform surface topography. There was no loss of tensile strength, or compliance and no evidence of thermo-mechanical degradation in the nanocomposite polymer. Compliance of the thoracic stent-graft was significantly better compared with ePTFE stent-graft (3.3±0.61 vs. 2.3±0.95 %/mm Hg x 10-2; P=0.0003). On MRI, there was no significant signal attenuation and no significant difference in flux between Valiant and nanocomposite polymer stent-grafts (102±2.27 vs. 99.8±2.4 ml/sec; P=0.33). Conclusions: A new endovascular stent-graft based on novel design and nanocomposite polymer with properties of compliance, viscoelasticity, anti-thrombogenicity and MRI compatibility has been developed. Sutureless technology with new biocompatible material bonded to Nitinol stents proved to be robust with no separation over accelerated 10-year cycle. These stent-grafts have the potential to address poor long-term durability, thrombogenicity, and compliance mismatch associated with present generation devices and reduce reintervention rate
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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