Development of Water-Soluble Polyesters for Tissue Engineering Applications

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce crosslinkable functional groups. A thermally-initiated crosslinking method was used to prepare hydrogels from the methacrylamide-functionalized polymers. The resulting hydrogels were assessed based on their physical and mechanical properties. High cell content (\u3e 95%) and Young’s moduli of 6 – 9 MPa were obtained were obtained for selected systems. Adipose derived stromal cells were encapsulated within these hydrogels and high cell viabilities indicated that they are promising as scaffolds for potential therapeutic or cell delivery. A second series of polyesters was prepared from PEG, Asp, and itaconic acid, thereby providing polymers with both crosslinkable moieties as well as functional groups for further bioconjugation. The backbone itaconate groups were crosslinked via thermally-initiated free radical crosslinking. Hydrogels were obtained, but the gel content was relatively low, indicating that further optimization of the polymer structure or crosslinking conditions will be needed in the future

Polyesters based on aspartic acid and poly(ethylene glycol): Functional polymers for hydrogel preparation

Hydrogels are commonly used as scaffolds for the preparation of three-dimensional tissue constructs and for the encapsulation and delivery of cells in regenerative medicine. Polyesters are an attractive class of polymers for hydrogel preparation. However, most polyesters have hydrophobic backbones and lack pendent groups that can be chemically functionalized. We describe here the development of water-soluble polyesters based on aspartic acid and poly(ethylene glycol) (PEG) (600 or 1500 g/mol), having pendent reactive amines. The reactivity of these amines with methacrylic anhydride, maleic anhydride, and itaconic anhydride was explored for the introduction of crosslinkable groups. The resulting methacrylamide-functionalized polymers were successfully crosslinked to form hydrogels using a redox-initiated free radical polymerization. The use of 10% (weight/volume) of polymer, and 10 mM of potassium persulfate and tetramethylethylenediamine led to high (\u3e97%) gel content, and compressive moduli of 13–21 kPa. Human adipose-derived stromal cells were encapsulated during the crosslinking process and exhibited greater than 80% viability in the hydrogels prepared from the polyester containing 600 g/mol PEG, with lower viability observed for the polymer containing 1500 g/mol PEG. These results support the potential for aspartic acid-based copolymers with short PEG chains in the backbone to serve as a platform for cell encapsulation, with additional opportunities for further functionalization available in the future

Flame Retardant Effect of Aerogel and Nanosilica on Engineered Polymers

Aerogels are typically manufactured vIa high temperature and pressure-critical-point drying of a colloidal metal oxide gel filled with solvents. Aerogel materials derived from silica materials represent a structural morphology (amorphous, open-celled nanofoams) rather than a particular chemical constituency. Aerogel is not like conventional foams in that it is a porous material with extreme microporosity and composed of individual features only a few nanometers in length with a highly porous dendriticlike structure. This unique substance has unusual properties such as low thermal conductivity, refractive index and sound suppression; in addition to its exceptional ability to capture fast moving dust. The highly porous nature of the aerogel's structure provides large amounts of surface area per unit weight. For instance, a silica aerogel material with a density of 100 kilograms per cubic meters can have surface areas of around 800 to 1500 square meters per gram depending on the precursors and process utilized to produce it. To take advantage of the unique properties of silica aerogels, especially the ultra light weight and low thermal conductivity, their composites with various engineering polymers were prepared and their flammability was investigated by Cone Calorimetry. The flammability of various polystyrene/silica aerogel nanocomposites were measured. The combination of these nanocomposites with a NASA patented flame retardant SINK were also studied. The results were compared with the base polymer to show the differences between composites with different forms of silica

Paper Session II-A - Polyimide Foam Insulation Materials for Aerospace Vehicles and Spaceport Applications

Advancements in high temperature materials by NASA have led to the development of polyimide foam systems with very attractive properties. The properties generated demonstrate the suitability of these materials for use as insulation for cryogenic fuel tanks on next generation vehicles, commercial and military ships, and potentially commercial aircraft. The significance of structural polyimide foams can be realized with a reduction in the overall weight of a launch vehicle. Due to a polyimide\u27 s high operating temperature ( \u27 \u27 260°C) structural polyimide foams can potentially reduce the amount of Thermal Protection System (TPS) and TPS integration structure that is required on launch vehicles. The lowtemperature elasticity of other polyimide foams is an enabling feature for many new cryogenic applications. These high performance materials also have properties that fulfill the demanding upcoming needs in ground support equipment for a Spaceport Technology Center. In a research study performed by Kennedy Space Center (KSC) and Langley Research Center (LaRC), polyimide foams were investigated for their physical, mechanical, thermal, and flammability properties. Variations in chemical structure, cell surface area, cell content and density on the resultant physical properties of the foams were studied. Data generated from this research revealed vital information involving foam technology and the interplay of factors such as foam density, open-closed cell content, surface area, and cell structure on the overall performance of the material. By controlling these parameters, new thermal insulation systems based on polyimide foam materials can be designed to meet demanding applications for spaceports and space vehicles

The complement receptor C5aR controls acute inflammation and astrogliosis following spinal cord injury

This study investigated the role of the complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI). C5ar(-/-) mice, which lack the signaling receptor for C5a, displayed signs of improved locomotor recovery and reduced inflammation during the first week of SCI compared with wild-type mice. Intriguingly, the early signs of improved recovery in C5ar(-/-) mice deteriorated from day 14 onward, with absence of C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, reduced myelin content, and more widespread inflammation at 35 d SCI. Pharmacological blockade of C5aR with a selective antagonist (C5aR-A) during the first 7 d after SCI improved recovery compared with vehicle-treated mice, and this phenotype was sustained up to 35 d after injury. Consistent with observations made in C5ar(-/-) mice, these improvements were, however, lost if C5aR-A administration was continued into the more chronic phase of SCI. Signaling through the C5a-C5aR axis thus appears injurious in the acute period but serves a protective and/or reparative role in the post-acute phase of SCI. Further experiments in bone marrow chimeric mice suggested that the dual and opposing roles of C5aR on SCI outcomes primarily relate to its expression on CNS-resident cells and not infiltrating leukocytes. Additional in vivo and in vitro studies provided direct evidence that C5aR signaling is required during the postacute phase for astrocyte hyperplasia, hypertrophy, and glial scar formation. Collectively, these findings highlight the complexity of the inflammatory response to SCI and emphasize the importance of optimizing the timing of therapeutic interventions

In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut

Complex microbial communities reside within the intestines of humans and other vertebrates. Remarkably little is known about how these microbial consortia are established in various locations within the gut, how members of these consortia behave within their dynamic ecosystems, or what microbial factors mediate mutually beneficial host–microbial interactions. Using a gnotobiotic zebrafish–Pseudomonas aeruginosa model, we show that the transparency of this vertebrate species, coupled with methods for raising these animals under germ-free conditions can be used to monitor microbial movement and localization within the intestine in vivo and in real time. Germ-free zebrafish colonized with isogenic P. aeruginosa strains containing deletions of genes related to motility and pathogenesis revealed that loss of flagellar function results in attenuation of evolutionarily conserved host innate immune responses but not conserved nutrient responses. These results demonstrate the utility of gnotobiotic zebrafish in defining the behavior and localization of bacteria within the living vertebrate gut, identifying bacterial genes that affect these processes, and assessing the impact of these genes on host–microbial interactions

Climate setting in sourcing teams: Developing a measurement scale for team creativity climate

Creative sourcing strategies, designed to extract more value from the supply base, have become a competitive, strategic differentiator. To fuel creativity, companies install sourcing teams that can capitalize on the specialized knowledge and expertise of their employees across the company. This article introduces the concept of a team creativity climate (TCC) - team members' shared perceptions of their joint policies, procedures, and practices with respect to developing creative sourcing strategies – as a means to address the unique challenges associated with a collective, cross-functional approach to develop value-enhancing sourcing strategies. Using a systematic scale development process that validates the proposed concept, the authors confirm its ability to predict sourcing team performance, and suggest some research avenues extending from this concept

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO