Tissue control rods for sheet-based tissue engineering

Abstract

The disclosure provides methods and systems for tissue engineering including an apparatus and methods for the growth, maintenance, and use of robust tissue sheets using tissue manipulation devices. The tissue manipulation devices provide a method of anchoring the tissue sheets to the cell culture substrate to promote prolonged maturation and subsequent increased mechanical strength. The tissue manipulation devices also provide a technique to facilitate removal of the sheet from the culture container and subsequent production steps to assemble more complex three dimensional organs from the robust sheet. The tissue manipulation devices also facilitate automated handling of the sheets in the assembly processes. The disclosure provides methods and composition derived from robust human sheets to build tissue engineered blood vessels, heart valves, stents, and endarterectomy patches and the like. The use of these tissue manipulation devices facilitates the assembly of complex tissue engineered organs using the novel sheet-based tissue engineering approach.

1 . A system for manipulation of a tissue in vitro, comprising: 
 a culture container comprising one or more wall, a bottom, and an upper opening, each of the one or more wall and the bottom having an inner and outer surface thereby forming an inside and an outside, the one or more wall and bottom comprised of a biocompatible material;    one or more tissue manipulation device comprising a first end and a second end and one or more wall, wherein the one or more tissue manipulation devices are substantially elongated from the first end to the second end, the one or more tissue manipulation device in juxtaposition with the one or more wall and/or bottom of the culture container;    growing a tissue comprising a population of adherent cells in the culture container in the presence of the one or more tissue manipulation device such that the population of adherent cells grow to form a tissue sheet in contact with one or more tissue manipulation device and wherein the cells contact the inside of one or more wall of the vessel; and    removing the tissue from the vessel using the one or more tissue manipulation device.