Visco-elasto-plastic modeling of small intestinal submucosa (SIS) for application as a vascular graft.

In developing new tissue engineered for vascular grafts, the mechanical properties of the material and its evolution once implanted are of utmost importance because they determine the regeneration of the vessel and the blood flow through the conduit. In fact, compliance mismatch is considered the main determinant of graft failure. In this research, we analyze the dynamic properties of the small intestinal submucosa (SIS), and propose and validate a constitutive model to fit the material's behavior. A uniaxial creep and recovery test was performed on SIS tubes to find the constitutive parameters. The model was composed by an elastic element in series with two Kelvin-Voigt solid elements and a plastic slider. The first elastic component was defined using Mooney-Rivlin strain energy function, while the plastic component was defined using a third-degree polynomial function of the plastic stress. The viscoelastic behavior was defined using the creep compliance formulation for the Kelvin-Voigt model. The parameters for the plastic and non-linear elastic elements followed a normal distribution, while the spring and dashpot constants of the visco-elastic element had a linear dependence on the load applied. The constitutive model was then used to simulate the SIS under the geometrical and pressure conditions found in native vessels for 1000 cycles at a frequency of 60 cycles per minute. From the cases simulated, performance curve charts were obtained in terms of the compliance of the material. These curve charts can be used as a predictive tool of the graft's behavior based on its geometry.

New Regenerative Vascular Grafts for Hemodialysis Access: Evaluation of a Preclinical Animal Model.

The purpose of this study was to evaluate a suitable animal model for the in vivo evaluation of patency and vascular tissue regeneration in small intestinal submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped SIS vascular graft was implanted between the internal carotid artery (CA) and the external jugular vein (JV) in five sheep and six swine. The U-shape grafts remained functional for 53 ± 4 days in sheep and 32 ± 2 days in swine. The sheep model presented exaggerated inflammation, so the swine model was selected for the in vivo study. Based on these initial results, a 4-mm C-shape SIS vascular graft with SIS circumferential reinforcement was developed to mechanically improve the vascular graft and manage complications identified during surgery in both sheep and swine. The C-shape vascular graft was implanted in a swine model (n = 3) between the CA and JV. GORE-TEX® vascular grafts were used as controls in the contralateral side of the neck. C-shape grafts remained patent for 47 ± 4 days, whereas the GORE-TEX® grafts were patent for 30 ± 15 days. The C-shape vascular graft was easier to handle during surgery, and its circumferential reinforcement improved in vivo patency, avoiding kinks in the graft after implantation. Histological results showed neovascularization and some regeneration with the alignment of endothelial cells in the vascular wall of the grafts. The model developed may be helpful in other research involving in vivo studies of vascular grafts for hemodialysis access.

Development and characterization of a novel porous small intestine submucosa-hydroxyapatite scaffold for bone regeneration.

The fabricated small intestine submucosa (SIS) - hydroxyapatite (HAp) sponges can act as biomimetic scaffolds to be utilized in tissue engineering and regeneration. Here we developed SIS-HAp sponges and investigated their mechanical, physical and chemical characteristics using scanning electron microscopy, Fourier transformed infrared spectroscopy, uniaxial compression, porosity, and swelling testing techniques. The results demonstrated mechanical properties superior to comparable bone substitutes fabricated with similar methods. SIS-HAp scaffolds possess an interconnected macroporosity, similar to that of trabecular bone, hence presenting a novel biomaterial that may serve as a superior bone substitute and tissue scaffold.