Artificial aortic valves: an overview.

This review discusses strategies that may address some of the limitations associated with replacing diseased or dysfunctional aortic valves with mechanical or tissue valves. These limitations range from structural failure and thromboembolic complications associated with mechanical valves to a limited durability and calcification with tissue valves. In pediatric patients there is an issue with the inability of substitutes to grow with the recipient. The emerging science of tissue engineering potentially provides an attractive alternative by creating viable tissue structures based on a resorbable scaffold. Morphometrically precise, biodegradable polymer scaffolds may be fabricated from data obtained from scans of natural valves by rapid prototyping technologies such as fused deposition modelling. The scaffold provides a mechanical profile until seeded cells produce their own extra cellular matrix. The microstructure of the forming tissue may be aligned into predetermined spatial orientations via fluid transduction in a bioreactor. Although there are many technical obstacles that must be overcome before tissue engineered heart valves are introduced into routine surgical practice these valves have the potential to overcome many of the shortcomings of current heart valve substitutes.

Retention of endothelium on ovine collagen biomatrix vascular conduits under physiological shear stress.

This study evaluates the adhesion of endothelial cells to 4 mm internal diameter, ovine collagen biomatrix vascular conduits. The biomatrix conduit is formed in a living animal and the wall consists of a complete, naturally produced matrix reinforced with polyester mesh. We propose that the microarchitecture of the matrix lining the lumen may promote endothelial cell attachment without pretreatment with adhesive proteins or extra cellular matrix components. Endothelial cell adhesion to the biomatrix surface was assessed by subjecting conduits seeded with ovine aortic endothelial cells (OAEC) to physiological range shear stresses of 16 and 32 dyn/cm2 in vitro. OAECs were isolated, cultured and seeded (1 x 10(6) cells/ml) by rotation onto the luminal surface of 20 cm lengths of biomatrix vascular conduits (n = 36). The seeded conduits were divided into three groups and cultured either for 24 h (n = 12), 48 h (n = 12) or 72 h (n = 12). Following culture, the conduits from each group were subjected to flow rates of either 240 ml/min (n = 6) or 480 ml/min (n = 6) with heparinized sheep blood for 1 h. Luminal surface cell cover was determined pre- and post-flow from Datura stramonium lectin labeled en face preparations. Histological analysis demonstrated that OAECs attach to the luminal surface of biomatrix conduits and form confluent monolayers within 24-48 h. Flow testing revealed that, for both flow rates and independent of the time in culture, there was no significant decrease in cell cover after flow (p = 0.13). The results support the hypothesis that a vascular conduit, engineered from a naturally formed biomatrix, provides a suitable substrate for the formation of flow resistant endothelium.

Adherence of human saphenous vein endothelial cell monolayers to tissue-engineered biomatrix vascular conduits.

This study investigates the adherence and retention under in vitro flow conditions of endothelium grown on the luminal surface of 4-mm-internal-diameter, biomatrix vascular conduits. The biomatrix vascular conduits are produced in living animals and consist of a naturally formed extracellular matrix wall incorporating a polyester mesh. We propose that the microarchitecture of the luminal surface may be conducive to endothelial cell (EC) seeding and to the formation of a firmly adherent endothelium without prior treatment of the surface with cell adhesives. ECs were isolated from segments of human saphenous vein and grown to confluence in a culture. Cultured cells were characterized by morphology and immunocytochemistry with anti-CD31, Von Willebrand factor, smooth muscle actin, cytokeratin, and the lectin Ulex Europaeus agglutinin. After culture, ECs were seeded (1 x 10(6) cell/mL) by rotation onto the luminal surface of 20-cm-long, biomatrix vascular conduits (n = 3). The seeded conduits were incubated for 72 h, and at set time points postseeding (1, 24, 48, and 72 h), the morphology, percentage luminal surface cover, and cell density (cell/cm(2)) were determined from en face preparations and histological cross sections. After 72 h in culture, the seeded conduits were subjected to a nonpulsatile flow for 1 h with culture media. A flow rate of 480 mL/min generated physiological-range shear stresses of 12 dyn/cm(2) on the endothelialized surface. After the flow, the conduits were fixed for histology, and the EC morphology and percentage luminal surface cover were determined. Quantification of the extent of luminal surface endothelialization, preflow and postflow, and cell densities at confluence was performed with digital imaging light microscopy and image analysis software. An analysis of the results demonstrated that confluent EC monolayers may be established on the luminal surface of biomatrix vascular conduits within 48 h. The formed endothelium was firmly adherent and was retained under physiological-range flow.

Recurrent haemolytic uraemic syndrome in a transplant recipient on orthoclone (OKT 3).

Recurrence of haemolytic-uraemic syndrome (HUS) after renal transplantation may occur in both cyclosporin A (CyA) and non-CyA-treated patients, and in patients receiving anti-lymphocyte globulin. We report a case of recurrent HUS in an 8-year-old boy who received Orthoclone (OKT3) combined with prednisolone and azathioprine therapy on receipt of his first cadaveric renal allograft. Despite avoidance of CyA therapy irreversible HUS occurred.