SPRAYABLE, BIODEGRADABLE POLYMER BLENDS FOR TISSUE ADHESION

Tissue adhesive materials can revolutionize surgical procedures, but they are often difficult to apply safely because of a required curing step where the viscous components of a glue solidify and become sticky. To simplify their deposition and improve their usability, this dissertation introduces tissue adhesive polymer blends that can be sprayed using a fiber production technique called solution blow spinning. The polymer blends studied here are innovative because they are non-curing: the polymer accumulates as a solid material directly on the tissue substrate of interest during spraying, quickly forming a strong bond. To achieve a rapid increase in tissue adhesion, we developed a surgical sealant composed of poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) that becomes adhesive in response to warming to body temperature. We then evaluated PLGA/PEG in small and large animal models of intestinal anastomosis and partial thickness skin wounds. Additional improvements to hemostasis, flexibility, and adhesion were made by incorporating micron-sized silica particles, which produced textured fibers with suppressed crack formation. We also developed the first pressure-sensitive tissue adhesive by formulating elastomeric copolymer blends with two components of different molecular weights. An additional objective of this dissertation was to study sprayable polymers that can be used as a controlled release system for various drugs. Towards this goal, we incorporated antimicrobial silver into solution blow spun PLGA/PEG fibers. At the optimal concentration, silver ions released over 14 days at levels that were effectively antimicrobial with minimal cytotoxicity. Coating strategies for controlling the delivery of polyelectrolyte complexes were also investigated

Dietary Ground Flaxseed Increases Serum Alpha-Linolenic Acid Concentrations in Adult Cats

We evaluated effects of dietary ground flaxseed on fecal and serum alpha-linolenic acid (ALA) concentrations, nutrient digestibility, and stool quality in female and male adult cats (n = 20 (8 males, 12 females); 3.95 ± 1.49 years of age (mean ± SD); 3.88 ± 0.82 kg BW). We hypothesized that adding ground flaxseed would increase serum ALA compared with feeding no flax, without changing nutrient digestibility. Cats were fed as-is 2.6% added-flaxseed (flax, n = 10) or no-flax (control, n = 10) diets (2.66 vs. 0.78% ALA of total fatty acids; crude protein 35%, fat 20%, fiber 3% as-fed) twice daily to maintain body weight for 28 days. Fecal collections were conducted on days 23–27 for total-tract nutrient digestibility, stool quality (scale 1–5; 1 = watery diarrhea, 5 = hard, dry, crumbly) and long-chain fatty acid (LCFA) analyses. Blood was collected on days 0, 14, and 28 for serum LCFA and chemistry analysis. Digestibility and fecal data were analyzed by ANOVA (SAS v9.4, Cary, NC, USA) and a repeated measures ANOVA for serum ALA. Flax-fed cats, compared with control-fed, had greater (p < 0.05) serum ALA after 14 days (4.00 vs. 0.71 µg/mL) and 28 days (7.83 and 3.67 µg/mL). No differences were observed in stool quality, and dry matter, protein, fat, and ALA digestibility. However, metabolizable energy was greater in the flax vs. control diet (4.18 vs. 3.91 kcal/g; p < 0.05). Overall, these data demonstrate that ground flaxseed added to cat diets increases serum ALA within 14 days, with no detriments to nutrient digestibility. We conclude that flaxseed can be used as a bioavailable source of ALA in cat diets

Evaluation of Two Dry Commercial Therapeutic Diets for the Management of Feline Chronic Gastroenteropathy

Management of feline chronic gastroenteropathies has included intervention with both veterinary therapeutic formulas designed to manage non-specific gastrointestinal disorders and those designed with limited novel or hydrolyzed ingredients for management of food-responsive enteropathies and steroid-responsive enteropathies (inflammatory bowel disease). There have been few studies evaluating the use of dietary intervention for the management of feline chronic gastroenteropathy. This prospective, multi-center study evaluated the use of two commercially available feline veterinary therapeutic dry diets designed to manage non-specific gastrointestinal disorders in 28 cats with a history of chronic vomiting and/or diarrhea. The majority of cats enrolled in the study had a history of vomiting (n = 25), with a smaller number having a history of concurrent diarrhea (n = 2) or diarrhea alone (n = 3). Cats were excluded if diagnostic tests identified any systemic or infectious disease that could be associated with the clinical signs of vomiting or diarrhea, and if they were panhypoproteinemic, hypoalbuminemic, hypocobalaminemic, or had a Spec fPL ≥5.4 µg/L. Cats were randomized to one of two veterinary therapeutic diets for 4 weeks. Feeding of both therapeutic diets resulted in a numeric reduction in the number of vomiting episodes over the 4-week period, but no significant differences were seen between dietary interventions. When looking within dietary groups, significant differences were seen in cats fed Diet A with reductions of 69.1, 73.3, and 63.2% (p values of 0.008, 0.003, and 0.029) in weeks 2, 3, and 4, respectively, when compared to week 0. The probability of vomiting also showed significant reductions in cats fed Diet A between weeks 0 and 2, 3, and 4, with odds ratios of 0.008, 0.005, and 0.005, respectively (p values of 0.038, 0.23, and 0.23). Results of this study demonstrate that a veterinary therapeutic gastrointestinal formula can be effective in the management of feline chronic vomiting. Cats that fail to respond to this dietary approach after a 2- to 4-week trial may benefit from a limited novel or hydrolyzed ingredient formula and may require additional diagnostics to better characterize the underlying disease

Biophysical Changes of Lipid Membranes in the Presence of Ethanol at Varying Concentrations

Ethanol is widely used as an additive to gasoline, and production of ethanol can come from single-celled organisms such as yeast. We systematically studied the influence of ethanol on common lipids found in yeast plasma membranes, specifically phosphatidyl­serine (PS), phosphatidyl­ethanolamine (PE), and phosphatidyl­choline (PC). Molecular dynamics simulations were used to probe changes to the biophysical properties of membranes with varying equilibrated bulk ethanol concentrations less than 25 mol %. The palmitoyl oleoyl (PO, 18:1/16:0) chain was used for all lipids, and a mixed bilayer of POPE/POPS (7:3 ratio) was also simulated. Ethanol was found to interact strongly with POPC, and thus its surface area per lipid, chain order, and electron density profiles differ the most from the neat bilayer. At 12 mol % ethanol in the bulk, ethanol penetrated into the hydrophobic core for all membranes studied, but POPC had the highest penetration. Although the anionic headgroup of POPS acted as a protectant for membrane structure compared to the zwitterionic lipids, this was not the case for the POPE/POPS mixture that showed more penetration of ethanol into the membrane than the single-component membranes. To fully characterize the impact of ethanol on yeast plasma membranes, our results suggest that experiments and simulations need to consider representative mixtures of lipids that exist <i>in vivo</i>