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Development of gelatin-silica hybrid hydrogels for bone tissue engineering and in vitro modelling
No full textNaturally derived biopolymers have received considerable attention for use as hydrogel materials for tissue engineering due to their innate ability to mimic the natural extracellular matrix. However, low mechanical strength and uncontrolled degradation limit their use within bone tissue engineering applications. Hybrid hydrogels are interpenetrating networks of organic and inorganic moieties and, when made via sol-gel processing, present an attractive route to address the drawbacks of biopolymers. Hybrid hydrogels can be classified as Class I (weak non-covalent interactions) and Class II (covalent bonds) depending on the interactions between the organic and inorganic component. This thesis presents the development of gelatin-silica organic-inorganic hybrid hydrogels using various organosilane crosslinkers to functionalise gelatin to provide covalent coupling of the organic and inorganic moieties. The efficiency and degree of functionalisation of gelatin with organosilane crosslinker were studied with various techniques (H NMR spectroscopy, ninhydrin assay and titration). Significant challenges with the functionalisation reaction, including hydrolysis and condensation of trimethoxysilyl groups, led to a lack of efficiency and low degree of functionalisation. A novel alternative method was developed to synthesise organosilane-functionalised gelatin; the reaction was rapid. Mechanical tests revealed the yield stress and toughness significantly increased in Class II hydrogels during ageing, suggested to be due to the continuous formation of a covalent network. However, the compressive mechanical properties of the hybrid systems were still far from those of bone (15 to 20 MPa). CryoSEM imaging revealed subtle differences in the microarchitectures of the different hydrogel formulations. When seeded on the Class II hydrogels, Saos-2 cells demonstrated improved cell spreading over a seven-day culture when imaged using actin/DAPI staining and cell penetration to depths of up to ~2,300 um as observed by light sheet fluorescence microscopy, compared to the Class I hydrogel. It is hypothesised that the dynamic mechanical properties and differences in microarchitecture of the Class II hydrogels, compared to Class I, were able to influence cell behaviour. Thus, the hybrid materials developed in this thesis could be utilised in soft tissue applications, as well as minimally invasive injectable hydrogels in spinal fusion and fracture repair
Postfeminism and the knife: cosmetic surgery accounts of young Thai women
Get PDFSince early 2010s, cosmetic surgery (CS) has come into vogue across Asia, including Thailand especially among women. Feminist scholars have extensively explored CS, with some of this scholarship underlain by the concept of postfeminism. Postfeminism centres around aesthetic/psychological/professional self-containment and self-empowerment, as well as self-monitoring and scrutiny from other women. Postfeminism has been increasingly examined concerning Asian locales. However, there has been scarce feminist research on not only young Thai women’s CS experiences, but also the applicability of postfeminism in the Thai context. This thesis thus aims to critically examine the reflective CS accounts of young Thai women through the lens of feminist theory. The research questions of this study are: 1) what informs young Thai women’s decisions to undergo CS?; 2) what are their post-operative experiences? To investigate these questions, semi-structured online interviews were undertaken with 50 young Thai women who had CS and five Thai cosmetic surgeons. The thesis has found that the reflective CS accounts of young Thai women are greatly underpinned by postfeminism, with several influences about Thai society and East Asian countries. These Thai and East Asian influences cohere with Chinese physiognomy; the collectivist and conservative basis of Thai society; Thai and Korean popular culture; and Korean and Thai-Chinese beauty styles. This thesis makes the prime theoretical contribution surrounding the entanglement between women’s self-confidence/esteem and looks; various characteristics of appearance-focused surveillance from men and women alike; and the distinctiveness of this project from postfeminist manifestations in the West
“Women writing self, gender, and the postcolonial nation – a brief study of the ‘new women’ phenomenon in south Asia”
Get PDFThe idea of the ‘women question’ and the ‘new woman’ phenomenon in middlebrow South Asian literature has drastically changed the complexities of womanhood. The Gandhian ‘new woman’ is curated to supplement the South Asian patriarchy and designed to accept the caste hierarchy. The phenomenon successfully presents itself as a postcolonial literary method to uplift women and the perception of women in Indian literature. However, it simultaneously and categorically removes subversive women based on religion, caste, and sexuality.
Progressive women writers have critically reshaped the ‘new woman’ phenomenon to include different types of womanhood by engaging with religion and understanding sexuality through religious dogma. This thesis studies select progressive Muslim woman writers and their struggle to question the modern literary and political praxis and hold these systems accountable. They rebelliously incorporate themselves into the more significant literary phenomena and political canons. However, the progressive writers, perhaps unknowingly, continue to produce literature within the Savarna framework (a hierarchy based on the caste system) of conjugality.
The Savarna women, or the bourgeoisie, continue to benefit from the status quo established by the Gandhian ‘new woman’ even after decades of literary changes. Subaltern women’s emergence and the political space that allows them to reiterate their lived-experiences jeopardise the benefits enjoyed by the bourgeoise by highlighting the intensity and nuances of South Asian postcolonial patriarchy, a unique structure explored later in this thesis. Subaltern voices, thus, are now the beacon of change in South Asian literature. This thesis explores this historical trajectory and the difficulties subaltern women face in the present to contribute to the literary lacunae
4D printing of Ni-Mn-Ga magnetic shape memory alloy through laser powder bed fusion
Get PDFNi-Mn-Ga magnetic shape memory (MSM) alloys represent a remarkable class of smart materials capable of undergoing reversible magnetic-field-induced strains (MFIS) of up to 10%. This unique property, characterised by rapid shape changes occurring within milliseconds, positions Ni-Mn-Ga alloys as promising candidates for a wide range of applications, including ultrafast actuators, sensors, micropumps, and energy harvesters. However, the substantial MFIS is predominantly observed in single crystals, primarily because grain boundaries act as barriers against twin boundary motion in polycrystalline materials. To overcome this limitation, research on reducing the impact of grain boundaries by creating porous and highly textured structures has been explored. The largest MFIS in polycrystals, up to 8.7% has been achieved in foam-like samples featuring ‘bamboo-like grains’—where grains are stacked on top of each other, spanning the diameter of the struts. These foam-like structures possess random porosity. Another promising approach is the manufacture of structures with ‘engineered porosity’, such as lattice structures. In these lattices, each strut is composed of a single large grain connected by nodes. This level of design freedom is achievable through additive manufacturing techniques, notably laser powder bed fusion (L-PBF).
This study focuses on the 4D printing (3D printing of smart materials) of Ni-Mn-Ga lattices using L-PBF. Initially, an attempt was made using an in-situ alloying powder blend, in order to gain compositional freedom, but this approach yielded inconclusive results due to segregations in the final part, which would negate the shape memory effect. Subsequently, an optimisation of process parameters was conducted using gas atomised powder for both bulk and lattice samples, with considerations made for Mn evaporation, density, and geometrical integrity. These samples exhibited a 14M crystal structure, not favourable for large MFIS. Following heat treatment, lattices featuring fully dense 200 μm diameter struts with a bamboo-like grain structure were successfully produced.
Further investigations focused on methods to enhance the crystallographic texture and control microstructure to increase the MFIS. These methods encompassed printing on a heated platform, using a double scanning strategy, and varying strut orientation according to the build direction. The study determined that the platform temperature and the double scanning strategy minimally impacted the microstructure and the magnetic behaviour, while the strut orientation had a substantial influence on the crystallographic texture and a small influence on the magnetic behaviour.
Additionally, the research explored the mechanical properties of Ni-Mn-Ga bulk and lattice samples fabricated through L-PBF, particularly in compression loading, with the intention of paving the way for future application prospects. Nanoindentation was used to determine the elastic moduli of both heat-treated and as-built lattices. The findings revealed that the samples exhibited brittle behaviour, with heat treatment increasing ductility but reducing strength. Notably, lattice samples fractured along a 45º diagonal and displayed significantly lower strength.
Lastly, this study underscores the potential of L-PBF in fabricating Ni-Mn-Ga lattices by demonstrating an MFIS of up to 6.6% in a lattice sample with a 10M crystal structure. These findings open up exciting possibilities for the application of functional Ni-Mn-Ga lattices in various fields
B cell characterisation in adult and paediatric liver diseases.
Get PDFB cells contribute to the pathology in many diseases such as autoimmune diseases and in many lymphomas. However, there is little literature on liver B cells in health and in disease for paediatric and adult liver diseases. Our aim was to characterise B cell subsets in adult and paediatric livers. We used multiparametric flow cytometry to identify B cell subsets in adult non-cirrhotic and cirrhotic livers, with cholestatic or metabolic disorders. We used immunohistochemistry and immunofluorescence to map the distribution of B cell subsets within liver tissue obtained from biliary atresia (BA) patients at the time of Kasai portoenterostomy (KPE, hilum tissue and wedge tissue from liver periphery) or during orthotopic liver transplantation (explant). We then carried out inflammation-focused transcriptomic analyses to identify differences between non-syndromic and syndromic BA patients and during disease progression. We found that CD24- B cells and age-associated B cells were detected across all adult end-stage liver diseases. We found that paediatric BA hilum samples had increased immune cell infiltration and the presence of B cell and lymphoid aggregates in both non-syndromic and syndromic cases. B cell and lymphoid aggregates mainly consisted of CD20+ CD24- B cells, and CD138+ antibody-secreting cells were rare. CD20+ CD24- B cells in B cell and lymphoid aggregates often expressed IL-6. Nanostring nCounter transcriptomics showed that the hilum was the site of active inflammation during KPE surgery, with pro-inflammatory cytokines being highly expressed. No remarkable differences in genetic profiles were observed between non-syndromic and syndromic BA patients, indicating that liver injury may be similar between the two groups. Our work showed that B cells may contribute to pathology in paediatric and adult liver diseases through the production of inflammatory mediators such as IL-6 and potentially through interactions with T cells. Lymphoid aggregates may also contribute to inflammation observed in the hilum. The hilum region is poorly studies in both adult and paediatric liver diseases and warrants further investigations
Defining neuroinflammatory pathways in cryptococcal meningitis
Get PDFCryptococcus neoformans is a fungus that is ubiquitous in the environment and can cause lethal meningitis in immunocompromised individuals, with deficits in T cell responses, such as HIV/AIDS, being particularly vulnerable. Cryptococcal meningitis (CM) causes approximately 100,000 deaths per year and those who do survive often suffer from long-term neurological disorders. Tissue-resident macrophage populations in the CNS are the first line of defence against invading pathogens. In this thesis, I have explored the early immune response in the brain when C. neoformans first invades, focusing on microglial responses and inflammation in the surrounding meninges. This work has shown that the immune response in the brain and meninges is generally delayed. In the brain, a unique population of microglia develops that hosts live C. neoformans and may contribute towards inflammation and interaction with lymphocytes. In the meninges, complement activation and macrophage-platelet interactions coincided with C. neoformans proliferation in this tissue. Taken together, this work demonstrates C. neoformans has evolved strategies to overcome innate immune responses at the brain borders and within the brain parenchyma. This has important implications for developing immune therapies to treat and prevent cryptococcal meningitis, as targeting adaptive immune defects may not be sufficient to prevent disease
A thematic Catalogue of British String Quartets of the early Twentieth Century and an account of the some of their contexts: 1890-1950
Get PDFFew string quartets were composed in Britain before the late nineteenth century, but from that time until the end of World War 2, the string quartet was one of the most crucial and vibrant genres in British music. The genre developed dramatically on account of promotion at public concerts, concerts at musical institutions, musical competitions, commissions, and the publication industries. This resulted in many British composers (including immigrants) writing string quartets, totalling approximately 600.
The thesis documents, describes and contextualises the string-quartet genre in Britain in the early twentieth century. A thematic catalogue provides basic information such as the full titles of pieces (with a work number, where applicable), year of composition and, if applicable, date of first (or first known) performances (live or broadcast), information on recordings of the work, the year of publication and the name of the publisher). Subsequent chapters provide context for the catalogue by investigating institutional history and string quartet repertoires that were performed in public and at musical institutions in London during the early twentieth century, as well as radio broadcasts. Overall the thesis focuses on quantitative approaches and broad trends in the repertory rather than sustained analysis or criticism of pieces by well-known composers, and avoids implicit judgements about value in relation to musical style
An investigation into the relationship between individual freedom and central government control within post-2010 free school proposals
Get PDFThis thesis considers the interface between individual freedom and central government control within the context of free schools created by the 2010 - 2015 Conservative-dominated coalition government. Free schools were positioned as a superior school-type, allowing leaders to utilise innovation for the benefit of parent-consumers. However, free school proposers needed to negotiate rules used by central government to approve suitable applications (application-assessment), and, once open, a regulatory framework applied to all state-funded schools. The tension between freedom and control is seen as one part of what Bourdieu described as a field, a bounded social space where key individuals, or groups, use power to control entry. The field reflects the dynamics of a relentless competition, defined through its doxa, or rules of the ‘game’. Reflexive Thematic Analysis (RTA) is used to analyse themes and thematic groups prominent within official-discourse, innovation practice within a random sample of ‘established’ free schools approved before the end of 2013, and testimony captured from interviews with individuals involved with free school applications. This provides insight into the ‘currency-value’ of the field, its doxa, and how individuals may have misrecognised the way rules controlling the ‘game’ could be seen as arbitrary. Analysis shows that successful proposers required existing credentials associated with a ‘good’ school or a ‘good’ multi academy trust. This ‘exchange-value’, defined by Central government, ensured that free schools met its needs, and therefore maintained the official cultural values of ‘good’ schools, ‘good’ pupils and ‘good’ teachers
Use of multicellular human liver models to investigate clearance of therapeutic antibodies
Get PDFBackground and Aims: Therapeutic antibodies make up the majority share of the drug industry, estimated to be worth $495 billion by 2030. Often, inadequate understanding of the tissue distribution and pharmacokinetics has resulted in many biotherapeutics being unable to attain clinical success. The liver plays a crucial role in the internalisation and catabolism of these antibodies due to their vast vasculature system and high expression of scavenger and Fc-receptors. Liver sinusoidal endothelial cells (LSEC) express many of these receptors and are known to contribute in the clearance of immune complexes. The liver is often susceptible to injury and disease, possibly leading to changes in key receptors involved in antibody clearance. Therefore, we wanted to explore the role of LSEC in health and disease and assess how they impact upon non-specific clearance of therapeutic antibodies.
Method: LSEC were isolated from diseased and normal human liver tissue to ascertain changes in receptor expression by qPCR, western blotting, and immunohistochemistry. A novel recycling assay was adapted to quantify the binding and clearance of 11 therapeutic antibodies at 4- and 8-hours by ELISA, flow cytometry and confocal microscopy. Pharmaceutical inhibitors were utilised to interrogate the internalisation mechanism of both healthy and cirrhotic LSEC and colocalisation with lysosomal markers were also performed to establish the end fate of these therapeutics.
Results and Conclusions: Our results confirm that LSEC express an extensive portfolio of receptors able to bind biotherapeutics, and the distribution of these receptors are significantly altered in disease. We have also demonstrated that LSEC not only internalise antibodies, but they can also partition these for lysosomal degradation. The rate at which this happens differs between healthy and diseased cells. Most importantly, we describe how cirrhotic LSEC favour internalisation via a receptor-mediated clathrin-dependent pathway, whereas healthy cells favour a clathrin-independent pinocytic mechanism. Therefore, we conclude cirrhosis alters pharmacokinetics and that the role of LSEC (both in health and disease) should be considered during antibody development
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