Nano-Acoustic Masonry of Microgels for Bottom-Up Tissue Engineering

SUMMARY Tissue engineering holds great promise for enabling alternative therapies for diseases such as diabetes, heart and liver failure. A common approach in tissue engineering is seeding cells in biodegradable scaffolds, which brings cells together in close proximity, aiming to mimic the native tissue environment. These scaffolds are expected to degrade and replaced by cellular growth and extracellular matrix deposition to generate a natural tissue. However, challenges remain with the current approaches, such as: 1) The inability to achieve a complex three- dimensional (3D) cellular architecture and organization (i.e. cardiac tissue is made of three major type of cells; i) cardiomyocytes ii) cardiofibroblasts, and iii) endothelial cells; 2) The limited control over cell-cell proximity with microscale resolution; 3) The inability to generate micro- engineered tissue constructs at high throughput with uniform cell distribution and high cell seeding density; 4) The lack of vascularity which results in cell necrosis and loss of function limiting the biologically relevant engineered tissues (i.e. diffusion length of metabolites is, typically, smaller than 300 micron). We hypothesized that engineered nanofilms can be used to assemble microgels into 3D constructs which can be integrated in a fluidic device to increase assembly throughput. The goal of this project is to address these challenges by developing a Microscale Acoustic System of Nanocoatings (MASON). In this proposal, we will merge directional nanocoating (i.e. ratchets) for transport of microgels, acoustic micro electro- mechanical systems (MEMS), and microscale hydrogel (microgel) fabrication technologies to achieve microgel assembly with controlled cellular architecture. We propose to build complex structures of biodegradable microgels in a microfluidic device based on directed assembly. Thus, the proposed novel microgel assembly approach presents a promising direction towards synthetic tissue engineering which is applicable to multiple organ systems. We expect to show that this novel approach will be significantly more efficient in addressing the problems outlined above than existing microgel assembly technologies.