Tissue engineering of small caliber vascular grafts

Objective: Previous tissue engineering approaches to create small caliber v ascular grafts have been limited by the structural and mechanical immaturit y of the constructs. This study uses a novel in vitro pulse duplicator syst em providing a 'biomimetic' environment during tissue formation to yield mo re mature, implantable vascular grafts. Methods: Vascular grafts (I.D. 0.5 cm) were fabricated from novel bioabsorbable polymers (polyglycolic-acid/po ly-4-hydroxybutyrate) and sequentially seeded with ovine vascular myofibrob lasts and endothelial cells. After 4 days static culture, the grafts (n = 2 4) were grown in vitro in a pulse duplicator system (bioreactor) for 4, 7, 14, 21, and 28 days. Controls (n = 24) were grown in static culture conditi ons. Analysis of the neo-tissue included histology, scanning electron micro scopy (SEM), and biochemical assays (DNA for cell content, 5-hydroxyproline for collagen). Mechanical testing was performed measuring the burst pressu re and the suture retention strength. Results: Histology showed viable, den se tissue in all samples. SEM demonstrated confluent smooth inner surfaces of the grafts exposed to pulsatile flow after 14 days. Biochemical analysis revealed a continuous increase of cell mass and collagen to 21 days compar ed to significantly lower values in the static controls. The mechanical pro perties of the pulsed vascular grafts comprised supra-physiological burst s trength and suture retention strength appropriate for surgical implantation . Conclusions: This study demonstrates the feasibility of tissue engineerin g of viable, surgically implantable small caliber vascular grafts and the i mportant effect of a 'biomimetic' in vitro environment on tissue maturation and extracellular matrix formation. (C) 2001 Elsevier Science B.V. All rig hts reserved.