Doctor of Philosophy, Case Western Reserve University, 2021, Biomedical Engineering

Post-surgical adhesions are internal scars that pathologically adhere together adjacent tissues/organs/biomaterials. They pose a tremendous but frequently underestimated burden across many surgical disciplines, being especially prevalent following abdominal surgery. Peritoneal adhesions can cause discomfort, intestinal obstructions, infertility, and increased morbidity/mortality of subsequent surgery. Once formed, treatments for adhesions tend to be risky and ineffective, so prophylactic strategies are desirable. Implantation of meshes, such as in hernia repair, often exacerbates peritoneal adhesions. Knitted polypropylene (PP) meshes are the most common hernioplasty devices, but are notoriously adhesiogenic owing to material and structural characteristics that promote incorporation, such as hydrophobicity and reticular construction. The ideal strategy to prevent mesh adhesions entails adhering a smooth, continuous, hydrophilic barrier material on the mesh visceral face to mitigate tissue attachment processes. Prior studies developed polymerized cyclodextrin (pCD) materials having unique capabilities for sustained, multi-window drug release, and suggested that these hydrophilic polymers passively resist cell attachment. In several animal species, pCD could deliver antibiotics for weeks to successfully resolve mesh infection, another hernioplasty complication for which only suboptimal solutions exist. In the present work, pCD materials were explored toward application as novel adhesion barriers for PP surgical meshes. First, nonthermal plasma activation was assessed as a strategy to improve PP-pCD bonding, as PP is generally unreceptive to coatings. Plasma introduced hydroxyls onto PP, enhancing PP-pCD adherence. Second, protein adsorption, bacterial attachment, and fibroblast viability/attachment upon pCD-coated and bare PP materials were evaluated. These events play roles in mesh adhesion, infection, and biocompatibility. pCD decreased protein adsorption and bacter (open full item for complete abstract)

Committee: Horst von Recum PhD (Advisor); Jeffrey Capadona PhD (Committee Chair); Kathleen Derwin PhD (Committee Member); Guang Zhou PhD (Committee Member); Michael Rosen MD (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, The Ohio State University, 2022, Biomedical Sciences

Regenerative medicine has the potential to revolutionize the field of surgical medicine. More specifically, tissue-engineered vascular grafts (TEVGs) offer a promising solution to current challenges associated with the use of synthetic conduits in cardiac diseases. Since its first use in humans back in 1999 numerous advances have been made describing the remodeling, performance, and outcomes of TEVGs; however, the barriers to its widespread adoption remain largely the same. First, there remains a tendency for the lumen of TEVGs to narrow due to excessive tissue formation. Second, an issue broadly implicated within the field of cardiothoracic surgery, is the development of adhesions following repeat operations thus hindering access and function. This dissertation seeks to overcome both issues through the application of novel therapeutic agents. The findings reported further advance mechanistic knowledge of the regenerative process that may one day improve outcomes of associated with tissue engineering.

Committee: Christopher Breuer (Advisor); Philip Binkley (Committee Member); Jeffrey Parvin (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Cellular Biology; Medicine

Doctor of Philosophy (Ph.D.), Bowling Green State University, 2012, Biological Sciences

Cellular edge features have been widely studied in recent years due to the interest in cell motility in normal and cancerous cells. Cues from cell interactions with the extracellular environment lead to overall cytoskeletal remodeling and consequently shape changes. The factors that determine the shape of a cell include actin polymerization, myosin II contraction and focal contacts (FCs). Actin based structures like lamellipodia (broad protrusions), ruffles (vertical protrusions) and filopodia (elongated, tapering protrusions) are the major protrusion types described in the scientific literature. However, their subjective classification is a problem when trying to understand mechanisms of protrusion formation in different cell types. The present study makes use of a previously determined computerized morphometric classification technique to distinguish features other than lamellipodia in 1000W rat tracheal epithelial cells. Some of the features identified through previous studies were factor 4, factor 5, factor 7 and factor 16. The aim of the present study was to explore the role of some of the structural components leading to the formation of a protrusion, particularly to a feature defined as factor 7. Integrated morphometry analysis with MetaMorph software was used to study the FC characteristics, while a geographical information system (GIS) software was used to study the FC orientation with respect to a protrusive feature. Small FCs favored factor 7 feature formation. High factor 7 values were observed when the class of FCs without actin became narrower. Paradoxically, where anchored actin cables on FCs showed a positive correlation with factor 7, the inner radius and width of the FC were the only elevated variables. The results suggested that certain populations of FCs with actin, which were narrow but varied in orientation, are important for factor 7 feature formation. It was observed that the most robust FCs with actin association were related to factor 5 val (open full item for complete abstract)

Committee: Carol Heckman PhD (Advisor); Jeffrey Snyder PhD (Committee Member); Peter Gorsevski PhD (Committee Member); Michael Geusz PhD (Committee Member); Roudabeh Jamasbi PhD (Committee Member) Subjects: Cellular Biology; Molecular Biology

Master of Science in Engineering, University of Akron, 2010, Chemical Engineering

Introduction: Adhesions following surgery represent a significant problem often resulting in pain, disability, and additional surgeries. Compounds are available for the prevention of postoperative adhesions, but effectiveness is difficult to assess; current models of adhesion comparison are limited to qualitative methods with much potential bias. Objectives: The objectives of the research performed were to create a quantitative model of adhesion strength assessment, to successfully encapsulate ketorolac tromethamine (KT) into poly(lactic-co-glycolic acid) microspheres, and to characterize of the microspheres for use in preventing adhesion formation. Quantitative Model Methods: The primary focus of this research was the creation of an adhesion complex that was suitable to quantitative testing using the Material Testing System (MTS™ System Corp, Eden Prairie, MN) machine platform. Following a midline infraumbilical laparotomy, bowel packing and retraction, and adequate exposure of the uterine horns and adjacent pelvic sidewall, a salpingostomy is made using electrocautery 1cm caudal the uterus-fallopian tube junction. A 7cm 8fr. latex urinary catheter, reinforced with a coaxial internal semi-rigid 5fr. polypropylene catheter, is inserted until it lies entirely within the lumen of the uterus. A 10cm segment of 6.35mm ID latex rubber drain tubing is secured to the dorsal aspect of the broad ligament medial the uterine horn; this is placed to prevent sidewall-broad ligament adhesion avoiding interference with the sidewall-uterus adhesion. The uterus and latex rubber drain are attached to the sidewall of the pelvis. The peritoneum lateral to the attached uterus is coagulated along the full length of the catheter insert at a setting of 6/10 (17W output) using a shielded electrocautery tip; cauterized area corresponds to the uterine horn lie and is limited to the peritoneum only. This injury is mirrored on the cannulated uterus to desiccate the superficial layer, (open full item for complete abstract)

Committee: Dr. Bi-min Newby (Advisor) Subjects: Engineering