Enhancing Cardiac Microbundle Stability for Improved In-Vitro Force Measurement

Project Description

Cardiovascular disease is the leading cause of death worldwide, yet breakthroughs in cardiac research remain challenging. Animal models fail to fully replicate human heart physiology, while studying live human hearts is ethically restrictive. Cardiac Microbundles (CMBs), composed of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiac fibroblasts (CFs), offer a promising in-vitro platform. These cells self-assemble into tissue that anchors onto a polydimethylsiloxane (PDMS) scaffold with two compliant pillars. The contractile force of CMBs, a key performance metric, is inferred from pillar bending.

A major challenge in this system is that CMBs frequently detach (“pop-off”) from the scaffold pillars during contraction. Features on pillar tops help stabilize CMBs, but increasing pillar size makes demolding difficult. A more feasible approach is to first fabricate scaffolds with standard pillar tops and then add stabilizing structures. Nanoscribe, a high-precision 3D printer, can produce micrometer-scale umbrella-shaped “cages” that attach to pillar tops, providing additional adhesion points for CMBs. However, the current press-fit method does not guarantee cage stability, which is essential for precise force measurements.

In this project, the REU student will learn scaffold fabrication and perform mechanical testing on scaffolds with cages to assess their stability. This research aims to improve in-vitro cardiac force measurement, advancing tissue-based cardiac studies.

 Mentors

Thomas Bifano, PI Ruifeng Hu

• Learn scaffold fabrication techniques, including PDMS molding and assembly.
• Explore methods to improve the fit of the cage on pillar tops to achieve stable attachment and minimize relative movement.
• Assess CMB performance on scaffolds with and without cages to evaluate the cage’s effectiveness in stabilizing the tissue.
• Gain hands-on experience with PDMS molding and the mold-making process.
• Develop a broad understanding of tissue engineering as a research field.
• Understand how researchers optimize experimental platforms, using the cage addition as a case study in designing, implementing, and evaluating system improvements.

Timeline

Week 1: Review literature and have a general understanding of cardiac tissue engineering.
Weeks 2-4: Learn basic PDMS molding skills
Week 5: Learn to assemble cage into scaffold
Weeks 6-9: CMBs will be seeded on scaffolds with cages. Mechanical measurements will be conducted on these scaffold
Week 10: Poster