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Biomaterials. 2018 Jun;167:1-14. doi: 10.1016/j.biomaterials.2018.03.012. Epub 2018 Mar 9.

Regeneration of diaphragm with bio-3D cellular patch.

Author information

1
Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. Electronic address: xiuying@pedsurg.med.kyushu-u.ac.jp.
2
Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
3
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
4
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Honjyo 1-chome, Honjyo-cho, Saga, 840-8502, Japan. Electronic address: nakayama@me.saga-u.ac.jp.

Abstract

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.

KEYWORDS:

Bio-3D printer; Congenital diaphragmatic hernia; Scaffold-free cellular patch; Skeletal muscle regeneration; Tissue engineering; Transplantation

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