Investigating the relationships between peristaltic contraction and fluid transport in the human colon using Smoothed Particle Hydrodynamics

© 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Complex relationships exist between gut contractility and the flow of digesta. We propose here a Smoothed Particle Hydrodynamics model coupling the flow of luminal content and wall flexure to help investigate these relationships. The model indicates that a zone of muscular relaxation preceding the contraction is an important element for transport. Low pressures in this zone generate positive thrust for low viscosity content. The viscosity of luminal content controls the localization of the flow and the magnitude of the radial pressure gradient and together with contraction amplitude they control the transport rate. For high viscosity content, high lumen occlusion is required for effective propulsion

Computational modelling of the behaviour of biomarker particles of colorectal cancer in fecal matter

Colorectal adenocarcinoma is one of the carcinogenic diseases that is increasing the morbidity and mortality rates worldwide. The disease initially occurs through the segregation of biomarker substances in the human system without manifesting symptoms that affect the health of the carrier. Early detection would allow the application of more effective treatments, less invasive procedures and reduce the development of cancer. The purpose of this investigation was the elaboration of a mathematical model and the development of computational simulations to visualize the behavior of biomarker particles in transit through the colon. The flow conditions, properties of the viscous medium and biological regions of interest were established. Constitutive models, numerical conditions and solution strategies were determined. A numerical grid was used to represent the model of the colon and the human feces that carry the bioparticles (biomarkers). The results indicated the trajectories of the bioparticles in the fecal mass and the interactive movement with the natural contractions of the colon. The analysis of the movement of the biomarker particles can provide future less invasive alternatives for the detection in real time of the cancer by means of the implantation of biosensors in the walls of the colon

Modelling and simulation of the hydrodynamics and mixing profiles in the human proximal colon using Discrete Multiphysics

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model). The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations

The effect of luminal content and rate of occlusion on the interpretation of colonic manometry

This is the accepted version of the following article: [Arkwright, J. W., Dickson, A., Maunder, S. A., Blenman, N. G., Lim, J., O’Grady, G., Archer, R., Costa, M., Spencer, N. J., Brookes, S., Pullan, A. and Dinning, P. G. (2013), The effect of luminal content and rate of occlusion on the interpretation of colonic manometry. Neurogastroenterology & Motility, 25: e52–e59.], which has been published in final form at [http://dx.doi.org/10.1111/nmo.12051]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Background Manometry is commonly used for diagnosis of esophageal and anorectal motility disorders. In the colon, manometry is a useful tool, but clinical application remains uncertain. This uncertainty is partly based on the belief that manometry cannot reliably detect non-occluding colonic contractions and, therefore, cannot identify reliable markers of dysmotility. This study tests the ability of manometry to record pressure signals in response to non-lumen-occluding changes in diameter, at different rates of wall movement and with content of different viscosities. Methods A numerical model was built to investigate pressure changes caused by localized, non-lumen-occluding reductions in diameter, similar to those caused by contraction of the gut wall. A mechanical model, consisting of a sealed pressure vessel which could produce localized reductions in luminal diameter, was used to validate the model using luminal segments formed from; (i) natural latex; and (ii) sections of rabbit proximal colon. Fluids with viscosities ranging from 1 to 6800 mPa s-1 and luminal contraction rates over the range 5-20 mmHg s-1 were studied. Key Results Manometry recorded non-occluding reductions in diameter, provided that they occurred with sufficiently viscous content. The measured signal was linearly dependent on the rate of reduction in luminal diameter and also increased with increasing viscosity of content (R2 = 0.62 and 0.96 for 880 and 1760 mPa s-1, respectively). Conclusions & Inferences Manometry reliably registers non-occluding contractions in the presence of viscous content, and is therefore a viable tool for measuring colonic motility. Interpretation of colonic manometric data, and definitions based on manometric results, must consider the viscosity of luminal content.Australian National Health & Medical Research Counci

Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.ope

Meshfree and Particle Methods in Biomechanics: Prospects and Challenges

The use of meshfree and particle methods in the field of bioengineering and biomechanics has significantly increased. This may be attributed to their unique abilities to overcome most of the inherent limitations of mesh-based methods in dealing with problems involving large deformation and complex geometry that are common in bioengineering and computational biomechanics in particular. This review article is intended to identify, highlight and summarize research works on topics that are of substantial interest in the field of computational biomechanics in which meshfree or particle methods have been employed for analysis, simulation or/and modeling of biological systems such as soft matters, cells, biological soft and hard tissues and organs. We also anticipate that this review will serve as a useful resource and guide to researchers who intend to extend their work into these research areas. This review article includes 333 references

Two case studies of SPH modelling in biological system: large intestine and deep vein valves

Computational Fluid Dynamics (CFD) techniques has proven its adaptiveness and mutuality in various application for diversified fields. At the moment, the investigation of physical mechanics developed by CFD in physiological transportation has arisen great attention. This thesis aims at deepening the insight into the interactive mechanism between the periodic deformable human conduits and the conveyed fluid content. To start with a coupled method consists of Smoothed Particle Hydrodynamics (SPH) method and Coarse-Grained Molecular Dynamics (CGMD) I Mass-spring modelling (MSM) is adopted as it has proven its potentials in dealing with the transportation inside the deformable solid boundaries. The fluid part is simply simulated by the SPH method while the soft solid boundaries are mimicked by another one to yield the optimal utility of the coupled method. Our models developed for Gastric Intestine (GI) system are first validated by comparisons with PET experimental outcomes and are applied to the practical usage. Quantitative analysis is made among simulations to illustrate the mixing and transportation of food propelled by the muscle peristalsis. Then the method is further extended into the study of the venous system and the results indicate a good interpretation of the pathological study of the valve dysfunction and the venous development