Design and fabrication of physiologic tissue scaffolds using projection-micro-stereolithography

Abstract

Recent advances in material processing are presenting groundbreaking opportunities for biomedical engineers. Projection-micro-stereolithography, or PuSL, is an additive manufacturing technique in which complex parts are built out of UV-curable resins using ultraviolet light. The primary strength of PuSL is its capacity to translate CAD files into three-dimensional parts with unusually small feature sizes (~0.5 microns). It is an ideal candidate, therefore, for making tissue scaffolds with sophisticated microscopic architecture. Nearly all multicellular biological tissues display a hierarchy of scale. In human tissues, this means that the mechanics and function of an organ are defined by structural organization on multiple levels. Macroscopically, a branching blood supply creates a patent network for nutrient delivery and gas exchange. Microscopically, these vessels spread into capillary beds shaped in an organ-specific orientation and organization, helping to define the functional unit of a given tissue. On a nano-scale, the walls of these capillaries have a tissue-specific structure that selectively mediates the diffusion of nutrients and proteins. To craft a histologically accurate tissue, each of these length scales must be considered and mimicked in a space-filling fashion. In this project, I sought to generate a cellular, degradable tissue scaffolds that mimicked native extracellular matrix across length scales. The research described here lays the groundwork for the generation of degradable, vascularized cell scaffolds that might be used to build architecturally complex multi-cellular tissues suitable for both pharmacological modeling and regenerative medicine.