Abstract 15594: Implantable Engineered Arteries From Human Dermal Fibroblasts and Fibrin Using a Multi-graft Cyclic Flow-Stretch Bioreactor
Tissue-engineered arteries based on entrapment of human dermal fibroblasts in fibrin gel yield completely biological vascular grafts that possess circumferential alignment characteristic of native arteries and essential to their mechanical properties. A bioreactor was developed to condition six grafts in the same culture medium while being subjected to similar cyclic distension and transmural flow resulting from pulsed flow distributed among the graft lumens via a manifold. The lengths of the grafts were incrementally shortened during bioreactor culture by adjusting the distance between the manifolds to maintain circumferential alignment and achieve mechanical anisotropy comparable to native arteries. After 7-9 weeks of bioreactor culture, the fibrin-based grafts were extensively remodeled by the fibroblasts into circumferentially-aligned tubes of collagen and other extracellular matrix with burst pressures in the range of 1400-2000 mmHg and compliance comparable to native arteries. The tissue suture retention force was suitable for implantation in the nude rat model and initial results from implant studies include a 6-month implant without evidence of aneurysm, minimal neo-intimal formation, and extensive formation of elastin lamellae resembling the native artery (see figure); there was mineralization in one location, however. Some 3-month implants were aneurysmal. Human blood-outgrowth endothelial cells (hBOEC) seeded on mature PFS-conditioned grafts maintained confluence under laminar flow at shear stresses up to the 80 dyne/cm2 in vitro. The burst strength achieved using a completely biological approach for tissue-engineered arteries in such short duration (2-3 months of graft culture) is unprecedented.
- © 2011 by American Heart Association, Inc.