Bioactivity of small intestinal submucosa and oxidized regenerated cellulose/collagen.

OBJECTIVE: This study examined the bioactivity of porcine small intestinal submucosa (SIS Wound Matrix [SISWM], USP) and oxidized regenerated cellulose/collagen (ORC). DESIGN: Bioactivity was assessed in vitro as the ability to stimulate neurite outgrowth in rat pheochromocytoma (PC12) cells, proliferation of human fibroblasts, secretion of vascular endothelial growth factor (VEGF) from human fibroblasts, and in an in vivo angiogenesis model. In the angiogenesis model, SISWM and ORC were implanted subcutaneously into the mice, and vessel ingrowth was assessed at day 21 after implantation using fluorescence microangiography and histology. MAIN OUTCOME MEASURES: The change in cellular differentiation, proliferation, growth factor secretion, and angiogenesis over the negative control was measured after exposure to SISWM or ORC. MAIN RESULTS: SISWM increased neurite outgrowth in PC12 cells by approximately 22% over negative controls and induced proliferation in 50.8% of human fibroblasts. These increases were comparable to positive controls. ORC was not active in either of these assays. SISWM also stimulated fibroblast VEGF secretion to a greater extent (422.4 pg/mL) than ORC (4.2 pg/mL) (P < .001). At 21 days, fluorescence microangiography showed dense infiltration of blood vessels in the SISWM that extended approximately 3 mm from the edge of the disc. In contrast, the ORC implant showed blood vessel incursion less than 1 mm from the edge of the disc, and it dissolved in the site. CONCLUSIONS: SISWM shows much greater bioactivity than ORC. This is likely related to its close structural and biochemical approximation to natural dermal extracellular matrix and may help explain the strong clinical successes of SISWM.

Absorption of bioactive molecules into OASIS wound matrix.

OBJECTIVE: To examine the ability of OASIS Wound Matrix to absorb, retain, and protect bioactive molecules from solution. DESIGN: Samples of OASIS Wound Matrix were incubated in solutions of bioactive molecules, specifically heparin, albumin, fibronectin, basic fibroblast growth factor 2, and platelet-derived growth factor (PDGF). Half of the samples were then rinsed, and all of the samples were evaluated using enzyme-linked immunosorbent assays (ELISAs) and dye-mediated spectrophotometric methods for absorption and retention of the bioactive molecules. Protection of PDGF was measured by placing PDGF-incubated and control samples into a degradation solution containing plasmin. Intact PDGF levels were then evaluated using a PDGF-specific ELISA. MAIN OUTCOME MEASURES: The main outcome measures were the amount of each bioactive molecule that was absorbed after incubation in solutions and retained after rinses as well as the amount of PDGF remaining after plasmin degradation. MAIN RESULTS: OASIS Wound Matrix absorbed bioactive molecules from solution, selectively absorbed PDGF from serum, and protected PDGF from protease degradation. CONCLUSIONS: Although OASIS Wound Matrix potentially has multiple functions in wound healing, it likely promotes wound healing, in part, by absorbing, retaining, and protecting bioactive molecules from the wound environment.

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.