Regeneration of diaphragm with bio-3D cellular patch

Zhang XY1, Yanagi Y2, Sheng Z3, Nagata K2, Nakayama K4, Taguchi T2
Source: Biomaterials
Publication Date: (2018)
Issue: 167: 1-14
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
Fibroblast, dermal (NHDF-Neo), human neonatal
Species: human
Tissue Origin: dermal
Skeletal Muscle Myoblast, (HSMM) human
Species: human
Tissue Origin: skeletal muscle


Neonates with congenital diaphragmatic hernia often require surgical defect closure with a patch. Alternatives to native diaphragmatic tissue are critically needed for this paediatric surgery. The clinical efficacy of mesh patches is limited by complications associated with residual foreign material and by hernia recurrence. In this study, we used a novel bio-3D printer method to generate large scaffold-free tissue patches composed of human cells. The resulting large tissue constructs had high elasticity and strength. Cellular patches were transplanted into rats with surgically created diaphragmatic defects. Rats survived for over 710 days after implantation of tissue constructs. CT confirmed complete tissue integration of the grafts during rat growth. Histology revealed regeneration of muscle structure, neovascularization, and neuronal networks within the reconstructed diaphragms. Our results demonstrate that created cellular patches are a highly safe and effective therapeutic strategy for repairing diaphragmatic defects, and thus pave the way for a clinical trial.