Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified cell culture model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and significantly accelerated cell mineralisation. Reduced representation bisulfite sequencing revealed that the shock wave altered methylation of gene promoters, leading to opposing changes in gene expression. Using a drug to target ITGAV, whose expression was perturbed by the shock wave, we found that we could abrogate the deposition of mineral in our model. These findings show how new therapeutics for the treatment of heterotopic ossification can be identified using cell culture models.

The pathophysiology of dilated cardiomyopathy (DCM), one major cause of heart failure, is characterized by the dilation of the heart but remains poorly understood because of the lack of adequate in vitro models. Current 2D models do not allow for the 3D organotypic organization of cardiomyocytes and do not reproduce the ECM perturbations. In this review, the different strategies to mimic the chemical, physical and topographical properties of the cardiac tissue affected by DCM are presented. The advantages and drawbacks of techniques generating anisotropy required for the cardiomyocytes alignment are discussed. In addition, the different methods creating macroporosity and favoring organotypic organization are compared. Besides, the advances in the induced pluripotent stem cells technology to generate cardiac cells from healthy or DCM patients will be described. Thanks to the biomaterial design, some features of the DCM extracellular matrix such as stiffness, porosity, topography or chemical changes can impact the cardiomyocytes function in vitro and increase their maturation. By mimicking the affected heart, both at the cellular and at the tissue level, 3D models will enable a better understanding of the pathology and favor the discovery of novel therapies.

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