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Patrick J Schaner

Publications and source records attributed to Patrick J Schaner.

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In vivo behavior of decellularized vein allograft.

BACKGROUND: We are investigating decellularized vein allograft as a scaffold to engineer a non-synthetic, small-diameter vascular graft. This study examines the in vivo behavior of this scaffolding after implantation into the arterial circulation. MATERIALS AND METHODS: Canine animals underwent bilateral carotid interposition grafting using jugular vein implanted as either: 1) fresh autograft, 2) fresh allograft, or 3) decellularized allograft. Decellularization was achieved using sodium dodecyl sulfate. Grafts were examined with duplex ultrasound biweekly to determine luminal diameter, thrombosis, stenosis, or anastomotic breakdown. After perfusion fixation at 2 or 8 weeks, grafts underwent histological, morphometric, and immunohistochemical examination. RESULTS: All animals survived without neurological or hemorrhagic complication. No deterioration of graft integrity (rupture, aneurysm) was observed in any group. Luminal narrowing was observed in both allograft groups, but secondary to different pathology. Fresh allografts had significant mononuclear cell infiltrate, intimal hyperplasia, and intramural hemorrhage consistent with rejection. Conversely, decellularized allografts had minimal evidence of rejection but instead had a compact fibrin layer formed along their lumen. This fibrin layer was absent in the peri-anastomotic regions where endothelium had migrated from the native artery. By 8 weeks, decellularized grafts had repopulated with cells staining positive for smooth muscle alpha-actin. CONCLUSIONS: After 8 weeks of arterial flow, decellularized vein allograft exhibits satisfactory strength, reduced antigenicity compared to fresh allograft, and supports cellular repopulation. These characteristics make it satisfactory for further tissue engineering; combined with luminal vascular cell seeding, it may prove useful as a small-diameter arterial bypass graft.

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Decellularized vein as a potential scaffold for vascular tissue engineering.

PURPOSE: Current strategies to create small-diameter vascular grafts involve seeding biocompatible, compliant scaffolds with autologous vascular cells. Our purpose was to study the composition and strength of decellularized vein to determine its potential as a vascular tissue-engineering scaffold. METHODS: Intact human greater saphenous vein specimens were decellularized by using sodium dodecyl sulfate (SDS). Residual cellular and extracellular matrix composition was studied with light and electron microscopy as well as immunohistochemistry. Burst and suture-holding strength was measured in vitro by insufflation and pull-through techniques. To assess initial handling and durability of decellularized vein in vivo, a canine model was developed wherein decellularized canine jugular veins were implanted as carotid interposition grafts in recipient animals. After two weeks of arterial perfusion, these grafts were studied with duplex imaging and histologic methods. RESULTS: Human saphenous vein decellularized by using SDS was devoid of endothelial cells and >94% of the cells resident within the vein wall. Collagen morphology appeared unchanged, and elastin staining decreased only slightly. Basement membrane collagen type IV remained intact. Compared with fresh vein, decellularized vein had similar in vitro burst (2480 +/- 460 mm Hg vs 2380 +/- 620 mm Hg; P >.05) and suture-holding (185 +/- 30 gm vs 178 +/- 66 gm; P >.05) strength. Decellularized canine vein functioned well in vivo without dilation, anastomotic complication, or rupture over 2 weeks of arterial perfusion. CONCLUSIONS: Vein rendered acellular with SDS has well-preserved extracellular matrix, basement membrane structure, and strength sufficient for vascular grafting. These properties suggest proof of concept for its use as a scaffold for further vascular tissue engineering. CLINICAL RELEVANCE: The following research examines the creation of a new small-diameter bypass graft. It is clinically relevant to patients who need distal arterial bypass, coronary artery bypass, or hemodialysis access, but who do not have adequate autologous vein for their surgeries. Future investigations will involve further tissue engineering of this vascular scaffold (eg, autologous endothelial seeding of its lumen) and testing the clinical usefulness of the completed graft.

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