Emergent remote stress-focusing drive submucosal collagen-fiber remodeling in intestinal anastomotic surgery

Abstract

Following resection of a diseased segment of intestine, a reconnection (anastomotic) geometry is chosen to reduce postoperative stress and optimize outcomes. As proper healing of an intestinal anastomosis is strongly affected by its mechanobiology, much attention has been devoted to the conical-structures formed along the suture-lines, where stress-focussing is expected. However, geometric considerations reveal that in addition to the obvious loci of stress-focusing, additional remote locations of stress-focusing may form. We identify conical-structures that inevitably form within regions of otherwise uninterrupted tissue. In this work we use geometric-analysis, finite-element-modeling, and in-vivo experiments to investigate these emergent stress-focusing structures, their mechanical stresses, and the resulting sub-mucosal collagen-fiber re-orientation, as these naturally arise in the side-to-side small-bowel anastomosis (SBA), the most common configuration performed in patients. Finite element modeling (FEM) predicts the appearance of remote high-stress regions. Allowing for tissue-remodeling, our simulations also predict increased dispersion of submucosal collagen fibers in these regions. In-vivo experiments performed on ten-week-old male C57BL/6 mice assigned the creation of side-to-side SBA or sham-laparotomy corroborate this result. Anastomoses were analyzed at sacrifice on post-operative day (POD) 14 and 88 with histologic-sectioning, staining, high-magnification-imaging, and submucosal collagen-fiber-orientation (κ) mapping. The mean and variance ofκ, a measure of fiber dispersion, at POD-14 far from the anastomosis show similar values to those obtained for sham-operated mice, while the FEM-predicted loci of stress-focusing display statistically significant higher values. The values at POD-88 at all loci show no statistically-significant difference, and agree with those of the sham-operated mice at POD-14.Significance StatementSide-to-side anastomosis is the most commonly used geometry for bowel anastomosis, and is generally believed to be the least stressed anastomosis of diamater-mismatched tubular limbs. Geometric considerations and finite element modeling reveal that when the anastomosed tissue is pressurized from its closed rest state to allow for content flow, stress-focusing conical-structures arise in otherwise uninterrupted tissue, away from the suture line. In-vivo study using mouse model reveal significant collagen-fiber remodeling in these stress focusing locations. These results guide….