Experimental tracheal replacement using tissue-engineered cartilage

Abstract

The authors tested the feasibility of using tissue-engineered cartilage, grown in the shape of cylinders, for replacing large circumferential defects of the cervical trachea in rats. Chondrocytes obtained from the shoulder of newborn calves were seeded onto a synthetic nonwoven mesh, 100 μm thick, of polyglycolic acid fibers 15 μm in diameter, cut into pieces of 2.5 × 4 cm. Twenty cell-polymer constructs were wrapped around silastic tubes and implanted into 10 nude mice for 4 weeks. Specimens were then excised and evaluated grossly and histologically for the presence of new cartilage, and biomechanically for their ability to resist collapse upon application of negative pressure. Six cylinders of tissue-engineered cartilage were then sutured into large circumferential defects created in the cervical tracheas of nude rats to replace the excised trachea. Implantation of cell-polymer constructs resulted in the formation of cylinders of hyaline cartilage. When placed within the lumen of a segment of bowel denuded of its mucosal lining, the hollow cylinders resisted collapse in all instances upon administration of negative 200 mm Hg pressure. The cartilage was grossly and histologically identical to that from which the cells had been initially isolated. Four of the six animals receiving these cartilage cylinders as tracheal replacements survived the procedure and were able to breathe in an unassisted fashion. Three of these animals never recovered fully from the anesthetic and the operation, and expired at 24, 48, and 72 hours. The fourth animal fully recovered from the procedure, and breathed spontaneously for 1 week, with no apparent limitations. Increasing respiratory distress then developed, and the animal died. Further studies are underway to develop composite structures of tubes lined by tracheal epithelium, with flexible cartilaginous rings as support.