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Mater Sci Eng C Mater Biol Appl. 2019 Jun;99:430-439. doi: 10.1016/j.msec.2019.01.047. Epub 2019 Jan 14.

An injectable, degradable hydrogel plug for tracheal occlusion in congenital diaphragmatic hernia (CDH).

Author information

1
Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Italy; INSTM - National Interuniversity Consortium of Materials Science and Technology, Firenze, Italy.
2
Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Italy.
3
Dipartimento di Elettronica, Informazione e Ingegneria Biomedica - DEIB, Politecnico di Milano, Italy.
4
NICU, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico - Università degli Studi di Milano, Italy.
5
Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Italy; INSTM - National Interuniversity Consortium of Materials Science and Technology, Firenze, Italy. Electronic address: lorenza.draghi@polimi.it.

Abstract

Congenital Diaphragmatic Hernia (CDH) is a birth defect characterized by failed closure of diaphragm, herniation of viscera in the thoracic cavity and impaired lung development. In most severe cases, fetoscopic endoluminal tracheal occlusion (FETO) is performed through a catheter-mounted balloon to contain pulmonary hypoplasia. To support the success rate of FETO and overcome some of the associated drawbacks, this work aimed at finding an injectable, degradable substitute for the balloon not requiring prenatal removal. Two different types of gels were evaluated as tracheal plugs: calcium-alginate and hyaluronan/methylcellulose blends (HA-MC). The effect of composition on hydrogel properties was evaluated, to identify formulations meeting design requirements. Anatomical tracheal casts were fabricated and filled with a simulated lung fluid to assess injectability, cohesiveness, sealing pressure and persistence of plugs. In vitro cytotoxicity and adhesion of mouse fibroblasts on hydrogels were also investigated. For both hydrogels, adjusting formulation enabled to obtain gelation time within the design range. Furthermore, when injected in the tracheal model, good cohesion and capability to adapt to the anatomical shape were also observed. Effective sealing up to 80 cm H20 was reached for selected compositions and was maintained for over 4 weeks in the in vitro model. Swelling and weight loss were also strongly influenced by composition and varied from few days to several weeks. Despite the absence of in vitro cytotoxicity, a favourably low cell-adhesion was observed for both hydrogels. However, due to their shear-thinning behaviour, HA-MC blends appeared as a particularly suitable candidate for single-surgery tracheal occlusion.

KEYWORDS:

Calcium alginate; Congenital diaphragmatic hernia; FETO; Injectable hydrogels; Methylcellulose/hyaluronic acid

PMID:
30889717
DOI:
10.1016/j.msec.2019.01.047

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