Biofilm formation on medical devices is responsible for a substantial portion of healthcare associated infections with approximately 99,000 deaths and estimated financial burden of $28-$45 billion annually. Given the long-standing challenges of biofilm eradication, physical and chemical surface modifications to prevent biofilm formation from the early adhesion stage, continue to gain momentum. Nanoscale structural features, ubiquitous in both natural and synthetic surfaces, are increasingly recognized to have wide-ranging effects on microorganism adhesion and biofilm development. In this thesis, bio-inspired nanofiber-coated polystyrene surfaces were developed to systematically investigate how highly ordered surface nanostructures (200nm-2000nm in size) impact adhesion and proliferation of model fungal pathogen, Candida albicans. A theoretical model for cell-textured surface interaction was also developed using thermodynamic principles to demonstrate that single cell adhesion to surface can be used to describe the population behavior. The trend for adhesion density of C. albicans on nanofiber-textured surfaces of varying diameters correlates with our theoretical finding of adherent single-cell energetic state. Findings from this thesis can be used for enhanced ab initio design of antifouling surfaces for medical applications and beyond. We demonstrate a successful prototypical example of reduction in biofilm formation by optimally designed nanofiber coating of urinary catheters. / Master of Science

Peritoneal adhesions occur in up to 93% of adults after peritoneal trauma during surgery. Most adhesions are asymptomatic but can cause female infertility, small bowel obstruction (SBO) and chronic abdominal pain. Adhesion prophylaxis is needed to reduce the significant morbidity and increased health care costs resulting from peritoneal adhesions. This thesis aims to establish a relevant and reproducible experimental adhesion model to simultaneously study the healing processs and adhesion formation and later to examine whether carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl scavenger, can reduce adhesion formation or not; and, in a long-term follow-up, to investigate the incidence of and identify risk factors for adhesive SBO requiring surgical treatment after laparotomy during infancy and to survey the prevalence of self-reported chronic abdominal pain and female infertility. Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Early elevation of IL-6, IL-1β and TNF-α concentrations in peritoneal fluid but not in plasma correlate to adhesion formation in this rodent adhesion model, indicating that anti-adhesion treatment should be early, local and not systemic. The animals were treated with either peritoneal instillation of PVAC, or the anastomosis was sutured with PVAC-impregnated resorbable polyglactin sutures. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly evaluated using Kennedy- and Nair scoring systems. PVAC-impregnated sutures reduced adhesion formation without reducing bursting pressure. Infants who underwent laparotomy between 1976 and 2011 were identified (n=1185) and 898 patients were included with a median follow-up time of 14.7 (range 0.0-36.0) years. The median age at first laparotomy was 6 (range 1.0-365.0) days. There were 113 patients (12.6%) with adhesive SBO, with the highest incidence found in patients with Hirschsprung’s disease (19 of 65, 29%), malrotation (13 of 45, 29%), intestinal atresia (11 of 40, 28%) and necrotizing enterocolitis (16 of 64, 25%). Lengthy duration of surgery (hazard ratio (HR) 1.25, 95% CI, 1.07 to 1.45), stoma formation (HR 1.72, 1.15 to 2.56) and postoperative complications (HR 1.81, 1.12 to 2.92) were independent risk factors. Chronic abdominal pain was reported in 180 (24.0%) of 750 patients, and 17 (13.8%) of 123 women reported infertility. The morbidity after laparotomy in neonates and infants is high. Awareness of the risk factors may promote changes in surgical practice.