Animal Models of Diverticulosis: Review and Recommendations

Patel, Bhavesh; Guo, Xiaomei; Noblet, Jillian N.; Chambers, Sean; Kassab, Ghassan S.

doi:10.1007/s10620-018-5071-y

Cited by 7 publications

(3 citation statements)

References 75 publications

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“…The material parameters established in our previous study were retained since, to our knowledge, it is the only study modeling a large animal colon under inflation and extension, the two major deformation modes of the colon. Moreover, it has been established that swine colon is relevant for diverticulosis study 33,37 . The selected material model and parameters are thus adequate choices for this study.…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of mechanical stress in colonic diverticulosis

Patel

Guo

Noblet

et al. 2020

Sci Rep

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Diverticulosis results from the development of pouch-like structures, called diverticula, over the colon. The etiology of the disease is poorly understood resulting in a lack of effective treatment approaches. It is well known that mechanical stress plays a major role in tissue remodeling, yet its role in diverticulosis has not been studied. Here, we used computational mechanics to investigate changes in stress distribution engendered over the colon tissue by the presence of a pouch-like structure. the objectives of the study were twofold: (1) observe how stress distribution changes around a single pouch and (2) evaluate how stress elevation correlates with the size of the pouch. Results showed that high stresses are concentrated around the neck of a pouch, and their values and propagation increase with the size of the pouch neck rather than the pouch surface area. These findings suggest that stress distribution may change in diverticulosis and a vicious cycle may occur where pouch size increases due to stress elevation, which in turn elevates stress further and so on. Significant luminal pressure reduction would be necessary to maintain stress at normal level according to our results and therapeutic approaches aimed directly at reducing stress should rather be sought after.

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Section: Discussionmentioning

confidence: 99%

Computational analysis of mechanical stress in colonic diverticulosis

Patel

Guo

Noblet

et al. 2020

Sci Rep

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“…Utilization of clinically relevant large animal models of diverticulosis is essential for advancing our understanding of diverticulosis pathogenesis and developing new therapies, especially with minimally invasive surgical interventions ( Patel et al, 2018 ). It is well known that collagen is the most abundant protein in mammals and serves to maintain the structural integrity of connective tissues ( Lord et al, 1977 ).…”

Section: Introductionmentioning

confidence: 99%

Novel patch biomaterial treatment for colon diverticulosis in swine model

Guo,

Patel,

Han

et al. 2023

Front. Bioeng. Biotechnol.

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Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3 months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.

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“…Indeed, swine is considered an ideal preclinical model system since swine and humans have many anatomic and physiological similarities in the digestive system. Moreover, we have shown that swine would be a suitable animal model based on criteria relevant to the pathogenesis of diverticulosis (23). In this study, we attempt to develop a swine model that would replicate the pathological process of diverticulosis.…”

Section: Introductionmentioning

confidence: 99%

Novel swine model of colonic diverticulosis

Guo

Patel

Han

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 ( n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 ( n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 ( n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30–75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis. NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.

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Animal Models of Diverticulosis: Review and Recommendations

Cited by 7 publications

References 75 publications

Computational analysis of mechanical stress in colonic diverticulosis

Computational analysis of mechanical stress in colonic diverticulosis

Novel patch biomaterial treatment for colon diverticulosis in swine model

Novel swine model of colonic diverticulosis

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