Abstract

Hydrogels are biomaterials that, thanks to their unique hydrophilic and biomimetic characteristics, are used to support cell growth and attachment and promote tissue regeneration. The use of decellularized extracellular matrix (dECM) from different tissues or organs significantly demonstrated to be far superior to other types of hydrogel since it recapitulates the native tissue’s ECM composition and bioactivity. Different muscle injuries and malformations require the application of patches or fillers to replenish the defect and boost tissue regeneration. Herein, we develop, produce, and characterize a porcine diaphragmatic dECM-derived hydrogel for diaphragmatic applications. We obtain a tissue-specific biomaterial able to mimic the complex structure of skeletal muscle ECM; we characterize hydrogel properties in terms of biomechanical properties, biocompatibility, and adaptability for in vivo applications. Lastly, we demonstrate that dECM-derived hydrogel obtained from porcine diaphragms can represent a useful biological product for diaphragmatic muscle defect repair when used as relevant acellular stand-alone patch.

Highlights

  • Tissue engineering approaches have been further developed and refined during the last years in order to produce organ and tissue substitutes for the treatment of several diseases [1,2,3,4]

  • We obtained a tissuespecific biomaterial able to mimic the complex structure of skeletal muscle (SKM) extracellular matrix (ECM), we determined hydrogel biocompatibility and biomechanical aptitude for in vivo application, and we demonstrated that decellularized ECM (dECM)-derived hydrogels obtained from porcine diaphragm represent a useful biological product to use as tissue patches for the treatment of diaphragmatic malformations, such as congenital diaphragmatic hernia (CDH)

  • All these results suggested that 1% w/v hydrogels can be obtained starting from diaphragmatic dECM, and the characteristics they possess in terms of ultrastructure and composition indicate a potential role as SKM mimicking scaffolds

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Summary

Introduction

Tissue engineering approaches have been further developed and refined during the last years in order to produce organ and tissue substitutes for the treatment of several diseases [1,2,3,4]. Several authors employed this technology for producing SKM dECMderived hydrogels, which can be used in different ways such as cell-laden constructs with. On the other hand, when hydrogels are used as filling material, especially in organs in which mechanical stress is significant, as in the SKM, control of the degradation rate and biomaterial mechanical properties are determining factors. In this latter situation, a variety of crosslinking strategies (chemical, physical, or with laser light) have been developed to increase hydrogel stiffness and strength with the aim of generating a substitute with the desired biomechanical characteristics [15,16]

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