Before the age of sensibility, the literary scaffold was a device, albeit one with its own set of associations. Its purpose was to arrest plot, create tension, and render character. Fictional representations of execution typically did not question the place of capital punishment in society. They were heroic events in which protagonists were threatened with a judicial device that was presumed righteous in every other case but their own. But in the eighteenth century, the fictional scaffold acquired new significance: it deepened a Gothic or sublime tone, tested reader and character sensibility, and eventually challenged the judicial status quo. The reliance on the scaffold to generate atmosphere, to wring our compassion, or to examine the legal value of the individual resulted in a new type of literature that I call scaffold fiction, a genre that persists to this day. Representations of execution in eighteenth-century tragedy, in Gothic narratives, and in novels of sensibility centered more and more on a hero’s scaffold anxiety as a means of enlarging pathos while subverting legal tradition. Lingering on a character’s last hours became the norm as establishment tools like execution broadsheets and criminal biography gave way to scaffold fictions like Lee’s The Recess and Smith’s The Banished Man—fictions that privilege the body of the condemned rather than her soul and no longer reaffirm the law’s prerogative. And because of this shift in the material worth of individuals, the revolutionary fictions of the Romantic era in particular induced questions about the scaffold’s own legitimacy. For the first time in Western literary history, representations of execution usually had something to imply about execution itself, not merely the justness of a particular individual’s fate. The first two chapters of my study are devoted to close readings of Georgian tragedy and Gothic novels, which provide a representative sample of the kinds of tropes particular to scaffold fiction (if they exist before the eighteenth century, they are less vivid, less present). The negotiation of a sentence, the last farewell, the lamentation of intimates, the imagined scaffold death of a loved one, and the taboo attachment of a condemned Christian to his flesh became more sustained and elaborate, opening up new arguments about the era’s obsession with sublimity, imagination, and sympathy, which in turn provide me with critical frameworks. The last two chapters pull back from the page in order to examine how literary representations of execution shifted as perspectives on the death penalty shifted. Anti-Jacobin fictions that feature the scaffold, for instance, were confounded by the device’s now vexed status as a judicial solution. Challenging the supposed authoritarian thrust of texts like Mangin’s George the Third and Craik’s Adelaide de Narbonne, the anti-Jacobin scaffold was swept up in a general reimagining of the object and its moral implication, which by extension helps to dismantle the reductive Jacobin/anti-Jacobin binary which critics increasingly mistrust. My final chapter devotes space to William Godwin, whose novels underscore the moral horror of the scaffold not just as the ultimate reification of the law’s power but, more interestingly, as the terminus of the “poor deserted individual, with the whole force of the community conspiring his ruin” (Political Justice). Godwin, a Romantic writer who anticipates Victorian and twentieth-century capital reforms, brings the scaffold fiction of writers like Defoe and Fielding into fruition as he wrote and agitated at the height of the Bloody Code, creating a template for Dickens, Camus and a host of modern authors and filmmakers.

Before the age of sensibility, the literary scaffold was a device, albeit one with its own set of associations. Its purpose was to arrest plot, create tension, and render character. Fictional representations of execution typically did not question the place of capital punishment in society. They were heroic events in which protagonists were threatened with a judicial device that was presumed righteous in every other case but their own. But in the eighteenth century, the fictional scaffold acquired new significance: it deepened a Gothic or sublime tone, tested reader and character sensibility, and eventually challenged the judicial status quo. The reliance on the scaffold to generate atmosphere, to wring our compassion, or to examine the legal value of the individual resulted in a new type of literature that I call scaffold fiction, a genre that persists to this day. Representations of execution in eighteenth-century tragedy, in Gothic narratives, and in novels of sensibility centered more and more on a hero’s scaffold anxiety as a means of enlarging pathos while subverting legal tradition. Lingering on a character’s last hours became the norm as establishment tools like execution broadsheets and criminal biography gave way to scaffold fictions like Lee’s The Recess and Smith’s The Banished Man—fictions that privilege the body of the condemned rather than her soul and no longer reaffirm the law’s prerogative. And because of this shift in the material worth of individuals, the revolutionary fictions of the Romantic era in particular induced questions about the scaffold’s own legitimacy. For the first time in Western literary history, representations of execution usually had something to imply about execution itself, not merely the justness of a particular individual’s fate. The first two chapters of my study are devoted to close readings of Georgian tragedy and Gothic novels, which provide a representative sample of the kinds of tropes particular to scaffold fiction (if they exist before the eighteenth century, they are less vivid, less present). The negotiation of a sentence, the last farewell, the lamentation of intimates, the imagined scaffold death of a loved one, and the taboo attachment of a condemned Christian to his flesh became more sustained and elaborate, opening up new arguments about the era’s obsession with sublimity, imagination, and sympathy, which in turn provide me with critical frameworks. The last two chapters pull back from the page in order to examine how literary representations of execution shifted as perspectives on the death penalty shifted. Anti-Jacobin fictions that feature the scaffold, for instance, were confounded by the device’s now vexed status as a judicial solution. Challenging the supposed authoritarian thrust of texts like Mangin’s George the Third and Craik’s Adelaide de Narbonne, the anti-Jacobin scaffold was swept up in a general reimagining of the object and its moral implication, which by extension helps to dismantle the reductive Jacobin/anti-Jacobin binary which critics increasingly mistrust. My final chapter devotes space to William Godwin, whose novels underscore the moral horror of the scaffold not just as the ultimate reification of the law’s power but, more interestingly, as the terminus of the “poor deserted individual, with the whole force of the community conspiring his ruin” (Political Justice). Godwin, a Romantic writer who anticipates Victorian and twentieth-century capital reforms, brings the scaffold fiction of writers like Defoe and Fielding into fruition as he wrote and agitated at the height of the Bloody Code, creating a template for Dickens, Camus and a host of modern authors and filmmakers.

A composite bioscaffold was constructed by encapsulating human decellularized adipose tissue (DAT) within a photopolymerized polysaccharide hydrogel towards the goal of forming an injectable scaffold for adipose tissue engineering. Methacrylated glycol chitosan (MGC) and methacrylated chondroitin sulphate (MCS) were investigated as the hydrogel base materials with varying DAT concentrations. Glycol chitosan and chondroitin sulphate were converted to photopolymerizable prepolymers through graft methacrylation using glycidyl methacrylate and methacrylate anhydride respectively to achieve a degree of substitution (DOS) of 15% and 16%, respectively. MGC and MCS gels containing 0, 3 and 5 w/v% cryo-milled DAT were fabricated and characterized by measuring sol content, equilibrium water content and compressive mechanical properties (n=4, n=3). An increase in stiffness and a decrease in sol and water contents were observed in the gels with higher DAT concentration, suggesting that the DAT was acting as a filler material that contributed to the crosslinking reaction. In vitro studies were conducted with primary human adipose-derived stem cells (ASCs) encapsulated in the DAT-polymer constructs to assess cellular viability (n=3, N=3) as well as adipogenic differentiation, quantitatively via glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity (n=3, N=3) and qualitatively through end-point RT-PCR analysis of key adipogenic genes (LPL, PPARγ, and CEPBα) (n=2, N=3) and intracellular lipid staining (n=3, N=3). Incorporating the DAT with MGC or MCS hydrogels enhanced cell viability as compared to the MGC and MCS scaffolds alone, with the MCS + 5 w/v% DAT scaffold having the highest overall cell viability and total cell number. The addition of the DAT in the MGC and MCS scaffold groups enhanced ASC adipogenesis as measured by an increase in GPDH levels, adipogenic gene expression and intracellular lipid accumulation characteristic of adipocytes. The highest GPDH levels were observed in the induced MCS with 5 w/v% DAT scaffolds, as compared to all other scaffold groups and tissue culture controls. The GPDH activity in this group increased by almost three times between 3 and 14 days, consistent with the progression of differentiation. The results indicated that the MCS-based scaffolds incorporating the DAT promoted cell viability and adipogenesis, demonstrating great promise as composite scaffolds for soft tissue regeneration. / Thesis (Master, Chemical Engineering) -- Queen's University, 2011-12-23 15:12:37.772

Before the age of sensibility, the literary scaffold was a device, albeit one with its own set of associations. Its purpose was to arrest plot, create tension, and render character. Fictional representations of execution typically did not question the place of capital punishment in society. They were heroic events in which protagonists were threatened with a judicial device that was presumed righteous in every other case but their own. But in the eighteenth century, the fictional scaffold acquired new significance: it deepened a Gothic or sublime tone, tested reader and character sensibility, and eventually challenged the judicial status quo. The reliance on the scaffold to generate atmosphere, to wring our compassion, or to examine the legal value of the individual resulted in a new type of literature that I call scaffold fiction, a genre that persists to this day. Representations of execution in eighteenth-century tragedy, in Gothic narratives, and in novels of sensibility centered more and more on a hero’s scaffold anxiety as a means of enlarging pathos while subverting legal tradition. Lingering on a character’s last hours became the norm as establishment tools like execution broadsheets and criminal biography gave way to scaffold fictions like Lee’s The Recess and Smith’s The Banished Man—fictions that privilege the body of the condemned rather than her soul and no longer reaffirm the law’s prerogative. And because of this shift in the material worth of individuals, the revolutionary fictions of the Romantic era in particular induced questions about the scaffold’s own legitimacy. For the first time in Western literary history, representations of execution usually had something to imply about execution itself, not merely the justness of a particular individual’s fate. The first two chapters of my study are devoted to close readings of Georgian tragedy and Gothic novels, which provide a representative sample of the kinds of tropes particular to scaffold fiction (if they exist before the eighteenth century, they are less vivid, less present). The negotiation of a sentence, the last farewell, the lamentation of intimates, the imagined scaffold death of a loved one, and the taboo attachment of a condemned Christian to his flesh became more sustained and elaborate, opening up new arguments about the era’s obsession with sublimity, imagination, and sympathy, which in turn provide me with critical frameworks. The last two chapters pull back from the page in order to examine how literary representations of execution shifted as perspectives on the death penalty shifted. Anti-Jacobin fictions that feature the scaffold, for instance, were confounded by the device’s now vexed status as a judicial solution. Challenging the supposed authoritarian thrust of texts like Mangin’s George the Third and Craik’s Adelaide de Narbonne, the anti-Jacobin scaffold was swept up in a general reimagining of the object and its moral implication, which by extension helps to dismantle the reductive Jacobin/anti-Jacobin binary which critics increasingly mistrust. My final chapter devotes space to William Godwin, whose novels underscore the moral horror of the scaffold not just as the ultimate reification of the law’s power but, more interestingly, as the terminus of the “poor deserted individual, with the whole force of the community conspiring his ruin” (Political Justice). Godwin, a Romantic writer who anticipates Victorian and twentieth-century capital reforms, brings the scaffold fiction of writers like Defoe and Fielding into fruition as he wrote and agitated at the height of the Bloody Code, creating a template for Dickens, Camus and a host of modern authors and filmmakers.

archives@tulane.edu / Off-the-shelf implantable biomaterials for tissue engineering and regenerative medicine (TERM) applications can treat numerous damaged organs/tissues. Such biomaterials have been investigated for their natural and synthetic biomimetic material properties to induce tissue regeneration in situ. Engineering biomaterials based off their mechanical properties like that of tensile strengths, porosity, nanofiber widths, or moduli can aid in tissue repair. However, tuning biomechanical properties alone is not always sufficient for biomaterials to induce effective tissue regeneration of large tissue/organ defects. The inclusion of biological properties to certain biomaterials such as stem/progenitor cells, growth factors, and/or cytokines can attenuate inflammation and stimulate proper tissue regeneration. In order to develop better off-the-shelf biomaterial implants for tissue repair, both the biomechanical and biological properties of the engineered biomaterial implant need to be assessed. In this dissertation, a decellularized polycaprolactone/chitosan hollow tube grown with MSC2s (De-PCL/CS) is investigated as a novel off-the-shelf tissue engineered graft (OTS-TEG) to repair hollow tubular organs like that of the esophagus. It is demonstrated that De-PCL/CS can retain extracellular matrix (ECM) factors from anti-inflammatory MSC2s post freeze-thaw decellularization. De-PCL/CS exhibits similar esophageal compressive biomechanics and is shown in an in vivo murine omentum model to be anti- inflammatory while robustly recruiting gastrointestinal (GI) cells. This gives great insight into De-PCL/CS as an immune modulating biomaterial to attenuate inflammation while promoting tissue repair for GI applications. Severe esophageal malignancies like esophageal cancer (EC), advanced Barrett’s Esophagus (BE), and pediatric atresia require GI reconstructive surgery (i.e. gastric pull up). De-PCL/CS has the translational capability as an implantable OTS-TEG to regenerate damaged esophageal tissue avoiding a gastric pull up. This not only increases the quality of life of the patient receiving this treatment but has an immediate potential impact of over $2.2 billion saved annually on the U.S. healthcare system. Nevertheless, the unique bioengineering patent-pending methods in developing De-PCL/CS allow it to be a platform OTS-TEG for treating a plethora of damaged organs/tissues. Translationally, De-PCL/CS can have a great therapeutic impact in the TERM global market that is expected to accrue over $100 billion by the mid 2020s. / 1 / Derek Cyrus Dashti

OBJECTIVES: This study aims to fabricate graded composite structures with different ceramic materials and explore the effect of the various ceramic materials on the microstructure, surface topography, crystal characterization, bioactivity, and mechanical properties of the ceramic scaffold. MATERIALS AND METHODS: Ceramic matrix specimens were prepared with a slip casting technique. After sintering, specimens were examined for their physical, chemical, and mechanical properties including microstructure, surface roughness, elemental composition, crystal characterization and biaxial flexural strength. Specimens from each group were immersed in a calcification solution and were evaluated for the deposition of calcium phosphate through microscopy, elemental analysis, and crystal characterization. RESULTS: Graded ceramic matrix materials were successfully fabricated using a slip-casting technique. Scanning electron microscopy revealed different surface topography as well as the deposition of calcium phosphate crystals on the specimen surface after immersion in calcification solution. Elemental composition and X-Ray Diffraction (XRD) spectra confirmed phase transformation in the composite specimen after sintering. Particle grain size significantly affected surface topography in terms of surface area roughness and topographical patterns. Moreover, the combination of alumina and bioactive glass improved mechanical properties compared to bioactive glass alone. CONCLUSIONS: 1. The ceramic matrix containing bioactive glass presented greater surface roughness compared to other ceramic matrix without bioactive glass. 2. Two crystal phases: tricalcium silicate (Ca3Si3O9) and calcium metasilicate (CaSiO3) were found in high temperature sintered bioactive glass. The combination of bioactive glass with alumina or hydroxyapatite presented another tricalcium silicate phase such as Ca3(SiO4)O. 3. The XRD analysis of the combination of alumina and hydroxyapatite detected two new phases including grossite (CaAl4O7) and calcium aluminophosphate (Ca9Al(PO4)7). 4. Ceramic matrix containing bioactive glass or hydroxyapatite presented greater deposition of calcium phosphate crystals while the combination of bioactive glass and hydroxyapatite showed the greatest amount of the precipitated crystals. 5. Alumina ceramic matrix showed the highest biaxial flexural strength while hydroxyapatite and bioactive glass presented low biaxial flexural strength. 6. The combination of alumina with hydroxyapatite or bioactive glass improved biaxial flexural strength. 7. The combination of hydroxyapatite with bioactive glass had lower biaxial flexural strength compared to a single-phase ceramic matrix.

Es wurde die Expression der osteogenen Markerproteine Alkalische Phosphatase, Bone Sialoprotein, Kollagen Typ I und Osteopontin von humanen mesenchymalen Stromazellen nach Kultur auf elektrogesponnenen Scaffolds analysiert. Die Scaffolds wurden mittels der Melt electrospinning writing Methode erstellt und unterschieden sich in ihrer Maschenweite. Anhand weiterer Kontrollversuche auf Monolayern wurde ein möglicher Einfluss der Geometrie auf die Proteinexpression untersucht. / The Expression of the marker proteins alkaline phosphatase, bone sialoprotein, collagen type I and osteopontin of human mesenchymal stromal cells after culture on electrospun scaffolds was analyzed. The scaffolds were made by the melt electrospinning writing method and differed in their mesh size. Further control experiments on monolayers were used to investigate the possible influence of the scaffolds´ geometry on the expression of the proteins.

In vorliegender Dissertationsarbeit wurde der Einfluss von MEW-gedruckten Scaffolds aus dem synthetischen Polymer PnPrOx, einem Poly(2-oxazolin), mit verschiedenen Oberflächenstrukturen (fibrillär, glatt) auf die Proteinexpression menschlicher Makrophagen untersucht. Dabei wurde überprüft, inwiefern die Beschaffenheit der Oberflächenstruktur des Polymers die Polarisierung von Makrophagen auf Proteinebene beeinflusst. / In this dissertation, the impact of MEW-printed scaffolds on protein expression in human macrophages was analyzed. These scaffolds were made of the synthetic polymer PnPrOx, a Poly(2-oxazoline), with different surface structures (fibrous, smooth). The aim was to evaluate in what way the surface structure of the polymer affects polarization of macrophages on a protein level.

Yes / The aims of this study were to develop a biological large diameter vascular graft by decellularisation of native human aorta to remove the immunogenic cells whilst retaining the essential biomechanical, and biochemical properties for the ultimate benefit of patients with infected synthetic grafts. Donor aortas (n = 6) were subjected to an adaptation of a propriety decellularisation process to remove the cells and acellularity assessed by histological analysis and extraction and quantification of total DNA. The biocompatibility of the acellular aortas was determined using standard contact cytotoxicity tests. Collagen and denatured collagen content of aortas was determined and immunohistochemistry was used to determine the presence of specific extracellular matrix proteins. Donor aortas (n = 6) were divided into two, with one half subject to decellularisation and the other half retained as native tissue. The native and decellularised aorta sections were then subject to uniaxial tensile testing to failure [axial and circumferential directions] and suture retention testing. The data was compared using a paired t-test. Histological evaluation showed an absence of cells in the treated aortas and retention of histoarchitecture including elastin content. The decellularised aortas had less than 15 ng mg−1 total DNA per dry weight (mean 94% reduction) and were biocompatible as determined by in vitro contact cytotoxicity tests. There were no gross changes in the histoarchitecture [elastin and collagen matrix] of the acellular aortas compared to native controls. The decellularisation process also reduced calcium deposits within the tissue. The uniaxial tensile and suture retention testing revealed no significant differences in the material properties (p > 0.05) of decellularised aorta. The decellularisation procedure resulted in minimal changes to the biological and biomechanical properties of the donor aortas. Acellular donor aorta has excellent potential for use as a large diameter vascular graft. / This study was supported by a Research and Development Grant (Grant Number 09-10-02-03) from NHS Blood and Transplant and through WELMEC a Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC, under Grant Number WT 088908/Z/09/Z

The research activity described in the present thesis is devoted to the design and development of porous bioactive ceramic scaffolds addressed to the regeneration of bone tissue and was mainly carried out at the Institute of Science and Technology for Ceramics, belonging to the National Research Council of Italy (ISTEC-CNR), during my Ph.D. in Civil, Environmental and Mechanical Engineering (Curriculum B: Mechanics, Materials, Chemistry and Energy). The regeneration of critical size bone defects is still an unmet clinical need and since decades the development of bioactive scaffolds, capable to instruct and guide bone cells to tissue regeneration is a major research area in material science, including interdisciplinary approaches spanning from the field of chemistry, engineering, biology and medicine. In fact, the currently used bio-inert devices (e.g. metallic devices) can merely provide a mechanical support without regenerating the damaged bone tissue and often inducing adverse side effects such as infections while forcing the patient to frequent revision surgeries, with relevant socio-economic impact. The main aim of my work was the design and optimization of new materials and processes to produce bioactive ceramics implants as potential solution for the treatment of large and load-bearing bone defects, particularly suitable for cranio-maxillofacial, orthopaedic and spinal surgery. In my activity I synthesized new hydroxyapatite-based materials, Ca10(PO4)6(OH)2, exhibiting ionic substitutions designed to mimic the inorganic part of bone, particularly magnesium, strontium, zinc and carbonate, which increase the osteogenic ability and the bio-resorbability, promote the physiological bone turnover, thus suitable also for osteoporotic patients, as well as the antibacterial ability. After a general introduction of bone tissue physiology and an overview on the analytical methods involved in the research (Chapter I and Chapter II, respectively), my thesis focuses on the development of various hydroxyapatite nanophases showing multiple ionic substitutions including strontium or zinc ions, in association with magnesium and carbonate, with the purpose to provide synergistic biological effects such as osteogenic and antibacterial ability, and induce microstructural changes potentially improving the mechanical performance (Chapter III). In this Chapter, an important role was played by sintering, that was investigated varying different parameters like temperature and atmosphere (Air, CO2). The influence of doping ions and conditions of sintering was evaluated by chemical-physical, biological and mechanical characterization in order to understand how the presence of doping ions and different conditions of sintering influence the osteogenic properties and the mechanical behavior of the hydroxyapatite scaffolds. Then, Chapter IV describes novel nanocrystalline, multi-doped hydroxyapatite phases with excellent osteoinductive character and anti-infective properties, evaluated in collaboration with University of Pavia. Physico-chemical analysis highlighted the role of the surface state and charge, as induced by the ion doping, in the enhancement of the biological features. Finally, Chapter V describes the preparation of 3-D devices endowed where the porosity could be controlled and tailored to achieve suitable compromise between mechanical properties and porosity extent, relevant for bone invasion and osteointegration. The devices are obtained via direct foaming of multi-doped hydroxyapatite ceramic suspension with high-energy planetary ball milling. This method enabled the development of large and complex shape porous scaffolds, recapitulating composition, porosity and structure of the natural bone, thus promising for future practical applications in bone surgery. A better understanding of how dopant ions affect the mechanical properties of these scaffolds has been made possible thanks to the several mechanical and microstructural tests performed on them.