From DFISpecific Aims/Letter of Intent

Since the advent of modern gastrointestinal (GI) surgery in the late 19thcentury, the problem of ‘leakage’ after surgical connections of adjacent tissue has remained one of the most dreaded complications and the cause of tremendous morbidity and mortality. While the idea of creating a tight surgical seal impermeant to bacterial infection or leakage of bowel contents sounds simple, the complexity of the biologic process is immense, involving inflammation, bacteria, blood flow and mechano-biology. However, while the rest of the field explores these potential mechanisms, we focus instead on a critical gap in our understanding: how does the underlying geometry of anastomotic construction link to healing? How does the mechanism linking tension or other forms of structural stress in tissue link with anastomotic integrity and shifts in the gut microbial environment? Surgical anatomy creates non-native tissue geometries, setting up mechano-geometric compatibility problems, leading to physical stresses in the surrounding tissue, and fundamental changes in the commensal and pathological relationships to bacteria. Surgeons are unaware of these incompatibility stresses and this lack of foundational knowledge linking surgical geometry to anastomotic healing makes it impossible for surgeons to define anatomic parameters that would allow them to optimize recovery from surgery. Part of the reason there is so little known about the geometry of anastomoses is that acquiring three-dimensional structural data of large volumes of tissue, often at the nanoscale, until recently, was impractical and close to impossible.

Our long-term goal is to quantitatively understand how the resulting geometry of anastomotic tissues influences local tissue biomechanics and bacterial interactions as a means to improve the outcomes of GI surgery. The specific objectives are to apply the cutting edge microscopic and algorithmic tools developed for large volume nanoscale tissue imaging at Argonne (Kasthuri) with expertise in surgery and its complications (Alverdy and Pocivavsek) to create the first model of tissue geometry after anastomotic surgery and its interactions with the microbiome.