Regeneration of the Diaphragm

The diaphragm is an essential mammalian skeletal muscle for respiration, comprising muscle, muscle connective tissue, tendon, nerves, and vasculature. Failed diaphragmatic development causes diaphragmatic defects in neonates. Neonates with congenital diaphragmatic hernia often require surgical defect closure with a patch. However, the clinical efficacy of patches is limited by complications associated with residual foreign material and by hernia recurrence. Engineered diaphragmatic repair is an emerging area of regenerative medicine in pediatric surgery. We fabricated scaffold-free cellular patches composed of human cells using the “Kenzan” method. The engineered cellular patches had a high elasticity and strength and were transplanted into rats with surgically created diaphragmatic defects. Diaphragmatic hernia was not observed in the animals, and no mortality was recorded during rat growth. Histology revealed regeneration of the muscle structure, neovascularization, and neuronal networks within the reconstructed diaphragms. Our results show that our newly created cellular patches are an extremely safe and effective therapeutic strategy for repairing diaphragmatic defects.