Abstract

3D Bioprinting Physiologically Relevant Human Infarct Models and Cardiac Patches

Pinar Zorlutuna, Sheehan Family Collegiate Professor of Engineering, University of Notre Dame

In the modern world, myocardial infarction (MI) is one of the most common cardiovascular diseases (CVDs) which are responsible for nearly 32% of all deaths causing almost 18 million people to die every year. Even though MI remains one of the leading CVDs, limited progress has been achieved with human MI models and therapeutic treatment options. 3D bioprinting has become one of the most powerful tools used to fabricate mimetic cardiac tissues, capturing the complexity of the native cellular composition and matrix structure. However, the generation of 3D tissue constructs with multiple cell types, matching mechanical properties, the ordered structure of the native extracellular matrix and the electroconductivity of the human heart remains a challenge in cardiac tissue engineering. To address the first two challenges, we developed novel bioinks combining gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels with decellularized human cardiac extracellular matrix (dhECM), and characterized them in terms of mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels, which corresponds to the difference between the stiffness of healthy cardiac tissue (8–12 kPa) and scar tissue (>150 kPa) formed after myocardial infarction (MI). Knowing that, we printed an infarct region model using a dual printhead by mixing iCMs with GE to model the healthy tissue and hCFs with GME to represent the scar tissue. To address the latter challenges, we developed a new composite construct that can provide both conductive and topographical cues for iCMs by 3D printing conductive titanium carbide (Ti3C2Tx) MXene in pre-designed patterns on polyethylene glycol (PEG) hydrogels, using aerosol jet printing, at a cell-level resolution and then seeded with iCMs and cultured for one week with no signs of cytotoxicity.