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.