Cell-by-cell construction of living tissue

Abstract

This paper outlines investigations into a potentially revolutionary approach to tissue engineering. Tissue is a complex 3D structure that contains many different biomaterials such as cells, proteins, and extracellular matrix molecules that are ordered in a very precise way to serve specific functions. In order to replicate such complex structure, it is necessary to have a tool that could deposit all these materials in an accurate and controlled fashion. Most methods to fabricate living 3D structures involve techniques to engineer biocompatible scaffolding, which is then seeded with living cells to form tissue. This scaffolding gives the tissue needed support, but the resulting tissue inherently has no microscopic cellular structure because cells are injected into the scaffolding where they adhere ta random. Wee have developed a novel technique that actually engineers tissue, not scaffolding, that includes the mesoscopic cellular structure inherent in natural tissues. This approach uses a laser-based rapid prototyping system known as matrix assisted pulsed laser evaporation direct write to construct living tissue cell-by- cell. This manuscript details our efforts to rapidly and reproducibly fabricate comlpex 2D and 3D tissue structures with MAPLE-DW by placing different cells and biomaterials accurately and adherently on the mesoscopic scale.