3D microfabrication of biological machines

Abstract

The burgeoning field of additive manufacturing, or “3D printing”, centers on the idea of creating three-dimensional objects from digital models. While conventional manufacturing approaches rely on modifying a base material via subtractive processes such as drilling or cutting, 3D printing creates three-dimensional objects through successive deposition of two- dimensional layers. By enabling rapid fabrication of complex objects, 3D printing is revolutionizing the fields of engineering design and manufacturing. This thesis details the development of a projection-based stereolithographic 3D printing apparatus capable of high- resolution patterning of living cells and cell signals dispersed in an absorbent hydrogel polymer matrix in vitro. This novel enabling technology can be used to create model cellular systems that lead to a quantitative understanding of the way cells sense, process, and respond to signals in their environment. The ability to pattern cells and instructive biomaterials into complex 3D patterns has many applications in the field of tissue engineering, or “reverse engineering” of cellular systems that replicate the structure and function of native tissue. While the goal of reverse engineering native tissue is promising for medical applications, this idea of building with biological components concurrently brings about a new discipline: “forward engineering” of biological machines and systems. In addition to rebuilding existing systems with cells, this technology enables the design and forward engineering of novel systems that harness the innate dynamic abilities of cells to self-organize, self-heal, and self-replicate in response to environmental cues. This thesis details the development of skeletal and cardiac muscle based bioactuators that can sense external electrical and optical signals and demonstrate controlled locomotive behavior in response to them. Such machines, which can sense, process, and respond to signals in a dynamic environment, have a myriad array of applications including toxin neutralization and high throughput drug testing in vitro and drug delivery and programmable tissue engineered implants in vivo. A synthesis of two fields, 3D printing and tissue engineering, has brought about a new discipline: using microfabrication technologies to forward engineer biological machines and systems capable of complex functional behavior. By introducing a new set of “building blocks” into the engineer’s toolbox, this new era of design and manufacturing promises to open up a field of research that will redefine our world.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste