Technological Approaches for Investigating Mechanotransductive Enterogenesis.

Enterogenesis;Short Bowel Syndrome;Shape Memory Alloy;Mechanical Engineering;Engineering;Mechanical Engineering

Utter, Brent AllenTeitelbaum, Daniel H. ;

University of Michigan

关键词: Enterogenesis;    Short Bowel Syndrome;    Shape Memory Alloy;    Mechanical Engineering;    Engineering;    Mechanical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/108850/brentu_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Short bowel syndrome (SBS) is a devastating condition characterized by insufficient small bowel length which leads to malnutrition and high rates of mortality. The treatment and management of SBS is difficult, and current approaches suffer from low success rates, lethal complications, and high costs. To improve the quality of care for SBS patients, of which there are approximately 40,000 in the USA, this research investigated technological approaches for a promising and novel treatment approach based on mechanotransductive enterogenesis, a process in which longitudinal small bowel tissue growth is induced by the application of tensile loading. Three enterogenesis device technologies were designed to attach to segments of small bowel tissue and extend, thereby placing the tissue under tension and inducing growth. Each device was used in experimental in vivo studies with clinically relevant porcine animal models to advance the knowledge of mechanotransductive enterogenesis for correcting SBS. The Curved Hydraulic Device was used to induce high expansion bowel lengthening, establishing the clinical feasibility of the mechanotransduction-based approach. The Instrumented Shape Memory Alloy Driven Ratchet, designed with the new Reset View Design Methodology and rack/pawl force interaction model, was used to develop the treatment approach by determining the limit of safely applied bowel tension, comparing the effect of applying different tissue expansion profiles on tissue growth, and exploring the limits of the maximum tissue expansion rate. Lessons from these studies led to the Reciprocating Linear Hydraulic Device, which was used to successfully demonstrate the viability of a high-expansion cyclical bowel lengthening approach by lengthening a segment of small bowel tissue by more than the device stroke. The success of this approach depended on the development of a clinically relevant tissue attachment approach, the Dilating Fenestrated Mesh, which was developed through the in vivo evaluation of a broad range of attachment approaches that characterized their attachment performance, ease of implantation/removal, and risk of causing surgical complications. This dissertation has made important contributions toward the advancement of this vital new treatment approach for SBS through the innovation of enterogenesis device technologies, the development of experimental methodologies, and an understanding of the mechanical device/tissue interaction.