Mimicking the Dystrophic Cardiac Extracellular Environment through DystroGel

This research introduces DystroGel, a cutting-edge biocompatible pathological hydrogel derived from decellularized dystrophic porcine heart tissue, suitable for tissue modeling applications. Rheological and proteomic analyses reveal structural and protein composition modifications, underscoring its unique properties. Notably, DystroGel influences gene expression of encapsulated fibroblasts, cardiomyocytes, and neurons, highlighting its bioactive biological potential to mimic the dystrophic ECM.

Abstract

Advances in understanding the mechanisms behind genetic diseases like Duchenne muscular dystrophy (DMD) underscore the critical role of the extracellular matrix (ECM) composition in disease progression. Effective in vitro models must replicate the intercellular relationships and physicochemical properties of native ECM to fully capture disease-specific characteristics. Although recent biomaterials support the in vitro biofabrication of pathophysiological environments, they often lack disease-specific ECM features. In this study, DystroGel, a hydrogel derived from the cardiac ECM of a porcine DMD model, replicates the distinct molecular composition of dystrophic cardiac tissue for the first time. The findings indicate that the dystrophic ECM matrix exhibits a unique protein profile, impacting cellular processes critical to DMD pathology. This work demonstrates the importance of using a 3D substrate that recreates intercellular dynamics within a defined pathological environment, enhancing the ability to model genetic disorders and providing a valuable tool for advancing personalized therapeutic strategies.