Development of polycaprolactone microparticles as a protein delivery system for the treatment of tendon disorders.

This thesis describes the development of a microparticle system, containing bioactive molecules for use in the regeneration of tendon tissue. An introduction is given into the cause of tendon injury and subsequent changes to the tissue post healing, as well as the shortcomings in treatments. The current state of the art in the field is given, including the use of cells and proteins for tissue engineering, polymer candidates for regenerative medicine, click chemistry for protein conjugation, and microparticles as drug delivery systems. The 3 results and discussion chapters highlight the successful synthesis of a microparticle system template that can conjugate proteins via an azide-alkyne click chemistry dibenzocyclooctyne linking unit. The synthesis of a novel polymer; polycaprolactone azide is described in chapter 2, showing the ability to conjugate to the linking unit in 30 minutes. Chapter 3 describes the subsequent use of the polymer for the formulation of microparticles via membrane emulsion technique. Microparticles from 10-153 μm were produced, with size controlled by altering process parameters such as stir speed and polymer concentration. A live/dead staining assay showed microparticles display no toxicity to tenocytes. The availability of the azide is demonstrated by the conjugation of an alkyne containing fluorescent compound to microparticles. Chapter 4 shows the successful conjugation of 4 proteins; bovine serum albumin, human serum albumin, transforming growth factor βeta 1 and 3 to microparticles. This reaction was efficient, with human serum albumin conjugation occurring in 10 minutes in physiological conditions. Two different linking molecules, with a conserved dibenzocyclooctyne core, were used. Attachment to the microparticles was via azide-alkyne click reaction and to protein via either an N-hydroxysuccinimide ester or thiol-maleimide reaction. Chapter 5 reviews the translation of academic research to a commercial product, supported by a 3-month studentship with Neotherix Ltd. Chapter 6 is a brief conclusion on the success of the project and future work that could be attempted to progress it further

Animation: textural difference and the materiality of Holocaust memory

The notion of “Holocaust animation” may seem paradoxical; how can a medium which, in the popular eye, is usually associated with comedy, play and fantasy be used to remember one of the 20th century’s most traumatic events? By examining the textural difference of animation to our lived world in texts such as Silence (Yadin and Bringas 1998) and I was a Child of Holocaust Survivors (Ann Marie Fleming 2010), it becomes clear how the medium can emphasise the fragile materiality of Holocaust memory. Adopting a methodology which blends transcendental phenomenology, as first outlined by Edmund Husserl, and existential phenomenology, brought into film studies in particular by Vivian Sobchack and Laura U. Marks, this paper considers the ability for animation to engage spectators with the materiality of memory, through bringing to the foreground a different way of experiencing the world to the quotidian

How can BTEC teachers support young people to be prepared for careers in the media industries? A reflection on pedagogy

There are major discrepancies between the skills required in the media industries, and those BTEC (Business and Technology Education Council) Level 3 students develop during their course. While academics have described these courses as ‘pre-vocational’, there is an expectation from students, parents and now the Government that BTECs, which are more practical than A Levels, will offer young people preparation for employment. However, there are distinct differences in the skills required by the media industries and those taught on such courses. While pre-existing literature acknowledges this issue in part, it does not offer potential pedagogical solutions. Recent reforms in vocational education will effect at policy level but offer little practical support for teachers. This action research project proposes potential teaching and learning strategies to help narrow the gap between BTEC media education (one of the most popular courses perceived to be vocational in the United Kingdom) and the skills particularly of high demand in today's industries. The project was organised as part of a Twenty-First Century Learning Alliance teacher research fellowship, which enables teachers to investigate problems that affect their own classroom practice

New ethical questions and social media: young people’s construction of Holocaust memory online

Much of the discourse about the ethics of Holocaust representation considers it a sacred event that imposes representational limits. Survivors are often considered “authorities” of Holocaust memory. However, Alasdair Richardson defines the Holocaust as an event “on the edge of living memory”: soon there will be no first-hand witnesses to share their stories. When the last survivor dies, the responsibility to remember will be entirely passed onto a new generation who cannot provide first-hand accounts of events; they did not literally witness this tragic past, but are called to “bear witness” in a more abstract sense as they remember the Holocaust through memorials, education and other media. While debates about the “appropriateness” of Holocaust representation have long-existed, the recent surge in online engagement with it complicates issues further and has led to the International Holocaust Remembrance Alliance (IHRA) launching social media guidelines for educators

Animation and memory

In Pixar’s Inside Out (Docter and Del Carmen, 2015), Joy and Sadness navigate around their host Riley’s long-term memory where coloured orbs representing different events in her past are stored on shelves. The film imagines memory as fixed content that can be recalled as needed. However, developments in the interdisciplinary field of memory studies now consider memory to be much more complex than this. Like the term realism discussed elsewhere in this volume, memory is a slippery thing – it is better understood as always in a state of becoming, as related to the present more than the past, and as a creative, networked process rather than as a simple transmission of historical data. After introducing some of the broad ideas related to contemporary studies of media and memory, this chapter focuses on the ways in which we can remember the past through and with animation, and how the form can represent memory, concentrating particularly on issues of trauma and witnessing, collective memory and identity, and nostalgia

A meta-media studies approach to digital pedagogy

No description supplie

A clinical, biological, and biomaterials perspective into tendon injuries and regeneration

Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics

A direct comparison of linear and star-shaped poly(dimethylaminoethyl acrylate) polymers for polyplexation with DNA and cytotoxicity in cultured cell lines

Poly[2-(Dimethylamino) ethyl acrylate] (PDMAEA) based polymers have been studied as potential gene delivery system. However, few reports emerging in literature suggesting that star-shaped PDMAEA based polymers are performing better in polyplexation with DNA, cytotoxicity and transfection, as compared to linear counterparts. Nonetheless, little evidences exist on direct comparison between the linear and star-shaped polymer structures. To address this, a series of new star-shaped PDMAEA polymers with linear counterparts were synthesised and directly compared their polyplexation with DNA and cytotoxicity in culture cell lines. The star-shaped PDMAEA polymers were synthesised using pentaerythritol tetrakis [2-(dodecylthiocarbonothioylthio)-2-methylpropionate] (4-arm DDMAT) RAFT agent in a “core-first” approach, whereas 2-(dodecylthiocarbonothioylthio)-2-methylpropionate was used to synthesise linear PDMAEA polymers. In order to investigate the effect of molar mass, both star-shaped and linear PDMAEA were synthesised in low (10kDa) and high (20kDa) molar mass. It must be noted here that the overall molar mass of the star-shaped polymer was equal to that of the linear counterparts. Interestingly, we found that the star-shaped polymer has slightly smaller hydrodynamic diameter (more compact) relative to linear counterparts, and importantly, star-shaped PDMAEA binds to DNA at much lower nitrogen to phosphate ratio (N/P ratio). However, the cytotoxicity studies in cultured 3T3 murine cell lines demonstrated that both star-shaped and linear counterparts have no toxicity at low 10kDa, but significantly toxic at higher 20kDa molar mass, this finding confirmed that the molar mass of PDMAEA play a key role in cytotoxicity effect, not variable polymer structures. Taken together, star-shaped PDMAEA binds more effectively to DNA than linear counterparts and showed no toxicity at 10kDa molar mass at variable polymer concentrations