Remodeling of suspended small intestinal submucosa venous valve: An experimental study in sheep to assess the host cells' origin

PURPOSE: To investigate the origin of host cells during remodeling of small intestinal submucosa (SIS) square stent-based bicuspid venous valves (VVs). MATERIALS AND METHODS: Suspended VVs (SVVs) were developed by suspending VVs within bare square stents so the valve elements would not contact the vein wall after deployment. Eight SVVs were placed within the intrahepatic and infrahepatic inferior venae cavae (IVCs) of four adult female sheep. Eight standard VVs were implanted in the external jugular veins of these animals for comparison. At 5 weeks after placement, the devices were examined for stability and patency and the animals were killed. Gross, histologic, and scanning electron microscopic (SEM) examinations were performed. RESULTS: Follow-up spot radiographs and venography showed no migration of the devices, venous occlusion, or thrombus formation. All SVVs were intact without contact with the IVC wall. Six VVs were competent and two were slightly tilted with some reflux. Histologic study showed remodeling of SVVs and VVs with newly formed collagen fibers; fibroblasts and inflammatory cells were found penetrating the SIS leaflets and endothelial cells on the surface. SIS neovascularization was also present. There was no difference regarding SIS remodeling between SVVs and the free part of VV leaflets. The VV leaflets' bases were thicker compared to their free parts (P < .01). SEM examination showed endothelial cells on both sides of the SVVs and VVs. Endothelialization of the SVV central leaflet surfaces and both surfaces of the VV leaflets was more complete than that of the peripheral surfaces of the SVV leaflets. CONCLUSION: SIS-based valve remodeling occurs independently of vessel wall contact by recruitment of cells directly from the circulation.