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Research: Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth

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Research: Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth

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 # 1Eugenia Carraro # 1 2Daniele Boso 1 3Arben Dedja 4Mattia Giagante 1 3Paola Caccin 2Raluca Ana-Maria Barna 3Silvia Bresolin 5Alice Cani 5Giulia Borile 6 7Deborah Sandrin 6 7 8Filippo Romanato 6 7 8Francesca Cecchinato 9 10Anna Urciuolo 8 9 10Dorianna Sandonà 2Paolo De Coppi 11 12Piero G Pavan 13 14Martina Piccoli 15Affiliations expand

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.

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