The biocompatibility of titanium cardiovascular devices seeded with autologous blood-derived endothelial progenitor cells

Abstract

Implantable and extracorporeal cardiovascular devices are commonly made from titanium (Ti) (e.g. Ti-coated Nitinol stents and mechanical circulatory assist devices). Endothelializing the blood-contacting Ti surfaces of these devices would provide them with an antithrombogenic coating that mimics the native lining of blood vessels and the heart. We evaluated the viability and adherence of peripheral blood-derived porcine endothelial progenitor cells (EPCs), seeded onto thin Ti layers on glass slides under static conditions and after exposure to fluid shear stresses. EPCs attached and grew to confluence on Ti in serum-free medium, without preadsorption of proteins. After attachment to Ti for 15 min, less than 5 % of the cells detached at a shear stress of 100 dyne/cm2. Confluent monolayers of EPCs on smooth Ti surfaces (Rq of 10 nm), exposed to 15 or 100 dyne/cm2 for 48 hours, aligned and elongated in the direction of flow and produced nitric oxide dependent on the level of shear stress. EPC-coated Ti surfaces had dramatically reduced platelet adhesion when compared to uncoated Ti surfaces. These results indicate that peripheral blood-derived EPCs adhere and function normally on Ti surfaces. Therefore EPCs may be used to seed cardiovascular devices prior to implantation to ameliorate platelet activation and thrombus formation.

Increased Yield of Endothelial Cells from Peripheral Blood for Cell Therapies and Tissue Engineering

“…Eight hours following each injection, the pigs underwent blood draws as previously described [16] and 60 ml of blood was anticoagulated with 20 ml citrate dextrose solution (Pall Corporation, CA, USA). The six pigs were divided into three groups of two pigs, with the order of the four injections randomized for each group (Figure 1).…”

“…We chose pigs for our in vivo study because of the following reasons: they are the preferred large animal model for cardiovascular diseases [15], we have previously characterized pBD-ECs and found them to be phenotypically and functionally analogous to human blood-derived ECs [6,16,17], and pigs enabled us to transplant autologous cells into the pigs’ aortae and inferior vena cavae (IVCs) to test cell functionality under flow in vivo. In vivo studies presented here provide proof-of-concept for utilizing DWBI and AMD3100-mobilized pBD-ECs for autologous cell therapies by demonstrating that pBD-ECs remain functional under flow on the surface of implanted intravascular titanium (Ti) tubes, prevent thrombosis in the IVC locally and also reduce the coagulation response systemically.…”

Endothelial Outgrowth Cells: Function and Performance in Vascular Grafts

“…46,60 Steady shear causes EOCs to increase eNOS gene expression 37,42,60 and NO production, suggesting an improved capacity to limit intimal hyperplasia. 37,58,61,75 Models that incorporate both fluid shear stress and inflammatory cytokines enable a better characterization of how these factors interact to influence EOC behavior. After 24 h of 6 dyn/cm 2 shear stress preconditioning, TNF-ainduced tissue factor activity of EOCs was reduced compared with non-preconditioned EOCs.…”

Biocompatibility Evaluation of Titanium Produced by Laser Rapid Forming

“…Biocompatibility is also known as biological acceptability 7) . Cytocompatibility is an important factor in biocompatibility 8) .…”