NPJ Regen Med
. 2022 Apr 25;7(1):25. doi: 10.1038/s41536-022-00222-x. https://pubmed.ncbi.nlm.nih.gov/35468920/
Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth
Edoardo Maghin # 1, Eugenia Carraro # 1 2, Daniele Boso 1 3, Arben Dedja 4, Mattia Giagante 1 3, Paola Caccin 2, Raluca Ana-Maria Barna 3, Silvia Bresolin 5, Alice Cani 5, Giulia Borile 6 7, Deborah Sandrin 6 7 8, Filippo Romanato 6 7 8, Francesca Cecchinato 9 10, Anna Urciuolo 8 9 10, Dorianna Sandonà 2, Paolo De Coppi 11 12, Piero G Pavan 13 14, Martina Piccoli 15Affiliations expand
- PMID: 35468920
- PMCID: PMC9038738
- DOI: 10.1038/s41536-022-00222-x
Free PMC article
Abstract
The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects.
© 2022. The Author(s).
