TISSUE ENGINEERING FOR DIAPHRAGMATIC RECONSTRUCTION

点击翻译按钮获取中文摘要

Congenital diaphragmatic hernia (CDH) is one of the most devastating anomalies afflicting the neonate. Visceral herniation associated with CDH results in fetal pulmonary hypoplasia often incompatible with life. Despite the previously dismal prognosis of babies with CDH, new technologies such as extracorporial membrane oxygenation, high frequency jet ventilation, and nitric oxide have extended survival past the peri-natal period. Fetal tracheal occlusion has provided a novel method to promote lung growth and potentially reverse pulmonary hypoplasia. Conclusive repair of the actual diaphragmatic defect responsible for the pathophysiology of CDH, however, still remains unsolved. Although a minority of diaphragmatic defects can be closed primarily, patch closure with polytetrafluoroethylene (PTFE) remains the standard of care. Despite its adequacy for closing the defect, long-term problems such as foreign body infection, recurrent herniation, and adhesions remain a problem with PTFE. The objective of this study is to utilize the principles of tissue engineering in order to develop a neodiaphragm for repair of congenital diaphragmatic hernia. Tissue harvested for the creation of the neodiaphragm will come from the same animal at an earlier point in its development, avoiding the problem of graft rejection. First, neonatal rat myoblasts and fibroblasts will be harvested and established in tissue culture. Next, a biodegradable polyglycolic acid matrix will be seeded with the expanded myoblasts and fibroblasts. Finally, a diaphragmatic defect will be created in a rat and immediately repaired with the biodegradable construct. We hypothesize that with the degradation and breakdown of the polyglycolic acid matrix the myoblasts and fibroblasts attached to the matrix will organize into a myofascial sheet recapitulating the original diaphragm. Similar methods have already been used in clinical practice to replace bladder and skin defects in the neonate. We hope to ultimately apply these methods toward diaphragmatic repair in human clinical trials.