Cardiac tissue injury during myocardial infarction often leads to congestive heart failure. The field of tissue engineering offers the promise of generating a muscle patch that would structurally and functionally repair tissue damage resulting from infarction or congenital heart defects. However, current cardiac tissue engineering techniques suffer from a number of limitations that preclude their use in clinical applications. In particular, safe and efficient repair of myocardial infarction requires that engineered cardiac tissue patch: 1) mimics the anisotropic (aligned) architecture of native cardiac muscle and 2) exhibits sufficient thickness (multiple muscle layers) in order to prevent dilation of the heart and improve its contractile function. Nevertheless, the method to engineer a 3D tissue patch with a cm2 area and uniform cell alignment throughout its volume is still non-existent, even for patches as thin as 50 ?m. This proposal will test the hypothesis that cultivation of cardiac cells within microfabricated porous hydrogel networks will improve the diffusion of nutrients and oxygen to embedded cells while simultaneously enabling control over local cell alignment.
The specific aims of this project are: 1) to develop methods to micropattern and stack thin porous cell/hydrogel networks into a relatively thick anisotropic cardiac tissue patch that will be cultured in a rotating bioreactor and 2) to assess the electrical and mechanical function of the resulting cardiac patch as a function of its thickness and micropatterned pore geometry. In the future, the methods developed in this study will be applied to clinically relevant cell types (e.g. embryonic stem cell-derived cardiomyocytes, skeletal myoblasts, mesenchymal stem cells, resident cardiac progenitor cells), and the resultant tissue patches will be assessed in animal studies for their ability to repair cardiac tissue damage and prevent the onset of heart failure.
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