Objective: Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source. The aim of the study was to assess the safety and feasibility of this technique for creating vascular tissue under low-pressure systems such as pulmonary artery or venous pressure.
Methods: Since September 2001, tissue-engineered grafts seeded with autologous bone marrow cells have been implanted in 42 patients. The patients or their parents were fully informed and had given consent to the procedure. A 5-mL/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. The polymer tube serving as a scaffold for the cells was composed of a copolymer of l -lactide and -caprolactone (50:50). This copolymer is degraded by hydrolysis. The matrix is more than 80% porous, and the diameter of each pore is 20 to 100 microm. Polyglycolic acid woven fabric with a thickness of 0.5 mm was used for reinforcement. Twenty-three tissue-engineered conduits (grafts for extracardiac total cavopulmonary connection) and 19 tissue-engineered patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median 5.5 years). All patients underwent a catheterization study, computed tomographic scan, or both, for evaluation after the operation. The patients received anticoagulation therapy for 3 to 6 months after surgery.
Results: Mean follow-up after surgery was 490 +/- 276 days (1.3-31.6 months, median 16.7 months). There were no complications such as thrombosis, stenosis, or obstruction of the tissue-engineered autografts. One late death at 3 months after total cavopulmonary connection was noted in patient with hypoplastic left heart syndrome; this was unrelated to the tissue-engineered graft function. There was no evidence of aneurysm formation or calcification on cineangiography or computed tomography. All tube grafts were patent, and the diameter of the tube graft increased with time (110% +/- 7 % of the implanted size).
Conclusion: Biodegradable conduits or patches seeded with autologous bone marrow cells showed normal function (good patency to a maximum follow-up of 32 months). As living tissues, these vascular structures may have the potential for growth, repair, and remodeling. The tissue-engineering approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. Longer follow-up is necessary to confirm the durability of this approach.