Engineering of contractible cardiac bilayer constructs using flexible silicon mesh scaffolds

Heart disease remains the leading cause of mortality worldwide. The potential for reversing heart tissue damage is highly dependent on the extent of injury and the timing of therapeutic intervention. Once permanent damage occurs, cardiomyocytes—cells with limited regenerative capacity – are replaced by non-contractile fibrotic tissue, resulting in scarring and a loss of contractile function in the affected regions of the heart.

Innovative approaches to cardiac regeneration, such as in vitro cardiac constructs, offer promising avenues for restoring heart function. These constructs integrate advances in stem cell technology, biomaterial scaffolding, and targeted delivery of bioactive molecules. A wide range of scaffolding materials has been explored, including natural polymers (e.g., collagen, fibrin, silk fibroin), synthetic polymers (e.g., polycaprolactone, polyurethanes, polyvinyl alcohol), decellularized extracellular matrices (from cardiac tissue, small intestinal submucosa, and urinary bladder matrix), and scaffold-free systems using cell sheets or organoid technologies.

Despite encouraging results in preclinical studies, several challenges remain before these constructs can be translated into clinical applications. An ideal scaffold must provide a supportive cellular microenvironment, sufficient mechanical strength, and flexibility to accommodate contraction. Incorporating electrical stimulation capabilities can further enhance functionality by promoting synchronized pacing and contractility.

This PhD project aims to explore the use of flexible silicon mesh as a novel substrate for engineering contractile cardiac bilayer constructs using myocardial and endocardial cells derived from human induced pluripotent stem cells (hiPSCs). The candidate will contribute to the development of the silicon mesh, optimization of cardiac differentiation protocols, and cultivation of cardiac cells or organoids on the mesh to assess biocompatibility, toxicity, and biodegradability. The formation and functionality of contractile bilayer constructs will be a key focus.