Integrated organ and tissue printing methods, system and apparatus

Abstract

A method of making an organ or tissue comprises: (a) providing a first dispenser containing a structural support polymer and a second dispenser containing a live cell-containing composition; (b) depositing a layer on said support from said first and second dispenser, said layer comprising a structural support polymer and said cell-containing composition; and then (c) iteratively repeating said depositing step a plurality of times to form a plurality of layers one on another, with separate and discrete regions in each of said layers comprising one or the other of said support polymer or said cell-containing composition, to thereby produce provide a composite three dimensional structure containing both structural support regions and cell-containing regions. Apparatus for carrying out the method and composite products produced by the method are also described.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 390,342; filed Oct. 6, 2010, the disclosure of which is incorporated by reference herein in its entirety.FIELD OF THE INVENTION[0002]The present invention concerns methods, systems, and apparatus for making tissues in vitro for subsequent implantation in vivo.BACKGROUND OF THE INVENTION[0003]Conventional organ printing technology (ink-jet printing) makes it possible to place viable cells in a three dimensional architecture. See, e.g., U.S. Pat. No. 7,051,654. And, various cells can be concurrently printed in an accurate manner. Because a tissue / organ has a complex structure, the organ printing technology is the most promising potential technology to mimic the anatomical structure of tissues or organs.[0004]However, with ink-jet cell printing techniques, the material being processed must be a low viscosity gel. As a result, high aspect ratio structures, or porous structures that facil...

AI Technical Summary

Benefits of technology

[0035]In some embodiments, the structural support polymer is dispensed from its corresponding nozzle at a temperature of at least about 25, 27, 30, 32, 35, 40, or 50 degrees Celsius (up to 80 or 100 degrees Celsius or more).

[0036]In some embodiments, the cell support composition(s) is / are dispensed from its corresponding nozzle at a temperature of not more than about 30, 27, 25, 23, 20, 17, 15 or 10 degrees Celsius (down to 5, 0, or −10 degrees Celsius, or less).

[0037]In some embodiments, the cell support composition(s) is / are dispensed from its / their corresponding nozzle at a temperature at least 3, 5, 7, 10, 12, 15, or 20 degrees Celsius less than the temperature at which the structural support polymer is dispensed through its / their corresponding nozzle(s).

[0038]A further aspect of the invention is a three dimensional tissue or organ construct comprising a solid support (e.g., in the form of a three dimensional, optionally porous, matrix) and a live cell-containing composition in separate and discrete regions therein, the construct optionally but preferably produced by the methods described herein. In some embodiments the construct may further contain pores, cavities, chambers, vessel lumens or channels formed therein, separately or interconnected with one another (e.g., by removal of sacrificial polymer regions). In some embodiments the construct may comprises a tissue composite (e.g., comprises two or more of skin / epithelium, bone, cartilage, skeletal muscle, tendon, and / or ligament tissue, etc; and / or two or more of endothelium and smooth muscle tissue). In some embodiments the composite comprises 2 or more different tissues, the two or more different tissues sharing a common, integrally formed and connected, solid support scaffold.

Problems solved by technology

As a result, high aspect ratio structures, or porous structures that facilitate the transport of nutrient and oxygen into the construct, cannot easily be achieved.

This is because the low viscosity materials being printed have relatively low mechanical stability.

In addition, the printing materials are easily deformed in liquid by swelling or shrinkage.

Hence, after implantation of tissue engineered scaffolds made by organ printing, it is difficult to preserve the pre-defined shape of the structure and protect immature cells or tissue therein.

The production of living organs and tissues by injection molding of forms generated by CAD / CAM has been described, but such methods again make the preservation of pre-defined shapes difficult.

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