Link: https://www.ncbi.nlm.nih.gov/pubmed/30851456

Acta Biomater. 2019 Mar 6. pii: S1742-7061(19)30173-4. doi: 10.1016/j.actbio.2019.03.007. [Epub ahead of print]
Allogenic tissue-specific decellularized scaffolds promote long-term muscle innervation and functional recovery in a surgical diaphragmatic hernia model.
Trevisan C1, Maghin E1, Dedja A2, Caccin P3, de Cesare N4, Franzin C5, Boso D6, Pesce P7, Caicci F8, Boldrin F8, Urbani L9, De Coppi P10, Pozzobon M1, Pavan P4, Piccoli M11.
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Abstract
Congenital diaphragmatic hernia (CDH) is a neonatal defect in which the diaphragm muscle does not develop properly, thereby raising abdominal organs into the thoracic cavity and impeding lung development and function. Large diaphragmatic defects require correction with prosthetic patches to close the malformation. This treatment leads to a consequent generation of unwelcomed mechanical stress in the repaired diaphragm and hernia recurrences, thereby resulting in high morbidity and significant mortality rates. We proposed a specific diaphragm-derived extracellular matrix (ECM) as a scaffold for the treatment of CDH. To address this strategy, we developed a new surgical CDH mouse model to test the ability of our tissue-specific patch to regenerate damaged diaphragms. Implantation of decellularized diaphragmatic ECM-derived patches demonstrated absence of rejection or hernia recurrence, in contrast to the performance of a commercially available synthetic material. Diaphragm-derived ECM was able to promote the generation of new blood vessels, boost long-term muscle regeneration, and recover host diaphragmatic function. In addition, using a GFP + Schwann cell mouse model, we identified re-innervation of implanted patches. These results demonstrated for the first time that implantation of a tissue-specific biologic scaffold is able to promote a regenerating diaphragm muscle and overcome issues commonly related to the standard use of prosthetic materials. STATEMENT OF SIGNIFICANCE: Large diaphragmatic hernia in paediatric patients require application of artificial patches to close the congenital defect. The use of a muscle-specific decellularized scaffold in substitution of currently used synthetic materials allows new blood vessel growth and nerve regeneration inside the patch, supporting new muscle tissue formation. Furthermore, the presence of a tissue-specific scaffold guaranteed long-term muscle regeneration, improving diaphragm performance to almost complete functional recovery. We believe that diaphragm-derived scaffold will be key player in future pre-clinical studies on large animal models.

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KEYWORDS:
Congenital diaphragmatic hernia; Decellularized tissue; Skeletal muscle; Tissue engineering

PMID: 30851456 DOI: 10.1016/j.actbio.2019.03.007
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