e-cone and d-cone singularities drive submucosal collagen fiber remodeling in intestinal anastomotic surgery

Following resection of a diseased segment of intestine, reconnection (anastomosis) is configured with varying geometry (i.e. end-to-end, side-to-side, etc.). Yet proper healing of an intestinal anastomosis is not only a function of its geometry, but also its mechanobiology. We aimed to investigate the intersection of geometry, mechanical stress, and submucosal collagen fiber re-orientation as it pertains to a side-to-side small bowel anastomosis (SBA), the most common configuration performed in patients. Ten-week-old male C57BL/6 mice were assigned to creation of a side-to-side SBA or sham laparotomy. Anastomoses were analyzed at sacrifice on postoperative day (POD) 14 and 88 with histologic sectioning, staining, high-magnification imaging, and submucosal collagen fiber orientation (κ) mapping. The κ data, a measure of fiber dispersion, for sham-operated mice shows a mean and variance of 0.110798 and 0.00078 respectively, in close agreement with those values measured far away from the anastomosis (far-field locations) for mice sacrificed at POD 14. However, the mean and variance of κ at geometric-focusing locations for POD 14 become statistically significantly higher when compared to the sham population. At POD 88, the measurements of κ at all locations show no statistically significant difference and are comparable to the values measured for the sham group and the measurements at POD 14 for the far-field locations (p=0.096). Insight into the in vivo findings were further developed using a finite element model (FEM) of a simulated side-to-side anastomosis to model collagen reorientation. FEM demonstrated that anastomotic opening for the accommodation of flow generated high-stress areas within the afferent and efferent limbs. Our simulations predicted increased dispersion of submucosal collagen fibers, which may help to alleviate non-homeostatic mechanical stresses. The consistency across our FEM and experimental measurements reveals an underlying dynamic interaction between mechanical stress and collagen remodeling. By integrating various biologic, geometric, and computational approaches, a more complete understanding of the active nature of anastomotic construction can be advanced.