Three-dimensional fabrication of biocompatible structures in anatomical shapes and dimensions for tissue engineering and organ replacement

• US 20070218544A1
• Filed: 03/14/2006
• Published: 09/20/2007
• Est. Priority Date: 03/14/2006
• Status: Active Grant

• Current Assignee: Agency For Science Technology and Research
• Original Assignee: Agency For Science Technology and Research
• Inventors: Schumacher, Karl, Kan, Shyi-Herng, Hsieh, Tseng-Ming, Ying, Jackie, Hock Loh, Jeremy
• Granted Patent: US 7,718,351 B2
• Time in Patent Office: Days
• US Class Current: 435/287.200
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

The present invention relates to methods and apparatuses involving biocompatible structures for tissue engineering and organ replacement and, more specifically, to methods and apparatuses involving biocompatible structures formed by three-dimensional fabrication for tissue engineering and organ replacement. In some embodiments, the biocompatible structures are scaffolds for cells that can be used as tissue engineering templates and/or as artificial organs. The structures may be three-dimensional and can mimic the shapes and dimensions of tissues and/or organs, including the microarchitecture and porosities of the tissues and organs. In some cases, a structure formed by three-dimensional fabrication comprises a wall defining a cavity and a plurality of pores in at least a portion of the wall. The pores may permeate the wall and enable exchange of a component (e.g., a molecule and/or a cell) between a portion interior to the cavity and a portion exterior to the cavity. For instance, pores may allow delivery of molecules, cell migration, and/or generation of connective tissue between the structure and its host environment. Structures of the invention can be implanted into a mammal, or alternatively and/or additionally, can be used ex vivo as bioartificial assist devices.

Claims

1. An article for use as a template for cell growth, comprising:

a structure comprising at least one wall defining a cavity; and

a plurality of pores having a cross-sectional dimension of less than 40 microns formed in at least a portion of the wall and permeating the wall, thereby enabling exchange of a component between a portion interior to the cavity and a portion exterior to the cavity,

wherein the structure is constructed and arranged for use as a template for cell growth.

2. A method as in claim 1, wherein the plurality of pores have a cross-sectional dimension of less than or equal to 20 microns.

3. A method as in claim 1, wherein the plurality of pores have a cross-sectional dimension of less than or equal to 10 microns.

4. A method as in claim 1, wherein the plurality of pores have a cross-sectional dimension of less than or equal to 1 micron.

5. A method as in claim 1, wherein at least a portion of the wall has a thickness of less than 30 microns.

6. A method as in claim 1, wherein the cavity has an inner diameter of less than 300 microns.

7. A method as in claim 1, wherein the article is formed by a process comprising multi-photon lithography.

8. A method as in claim 1, wherein the article is formed by a process comprising two-photon lithography.

9. A method as in claim 1, wherein the plurality of pores and the structure are fabricated by the same process.

10. A method as in claim 1, wherein the structure comprises a first cavity portion having a first inner diameter and a second cavity portion having a second inner diameter.

11. A method as in claim 10, wherein the first and second inner diameters are different.

12. A method as in claim 11, wherein the ratio of the first inner diameter to the second inner diameter is greater than 10:

1.

13. A method as in claim 1, wherein structure comprises a substructure.

14. A method as in claim 13, wherein the ratio between an inner diameter of the structure to an inner diameter of the substructure is greater than 10:

1.

15. A method as in claim 13, wherein the substructure comprises a wall defining a cavity.

16. A method as in claim 15, wherein the wall of the substructure comprises a plurality of pores formed in at least a portion of the wall and permeating the wall, thereby enabling exchange of a component between a portion interior to the cavity of the substructure and a portion exterior to the cavity of the substructure.

17. A method as in claim 16, wherein the portion exterior to the cavity of the substructure comprises the portion interior to the cavity of the structure.

18. A method of forming an article for use as a template for cell growth, comprising using a multi-photon lithography process to form a structure comprising at least one wall defining a cavity, wherein the wall comprises a plurality of pores having a cross-sectional dimension of less than 40 microns in at least a portion of the wall and permeating the wall, thereby enabling exchange of a component between a portion interior to the cavity and a portion exterior to the cavity.

19. An article for use as a template for cell growth, comprising:

a structure comprising at least one wall defining a cavity, the cavity having an inner diameter of less than 300 microns; and

a plurality of pores formed in at least a portion of the wall and permeating the wall, thereby enabling exchange of a component between a portion interior to the cavity and a portion exterior to the cavity,

wherein the structure is constructed and arranged for use as a template for cell growth.