Devices, systems, and methods for the fabrication of tissue utilizing UV cross-linking

• US 10,174,276 B2
• Filed: 10/20/2016
• Issued: 01/08/2019
• Est. Priority Date: 04/20/2012
• Status: Active Grant

• Current Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Original Assignee: Organovo Inc. (Organovo Holdings, Inc.)
• Inventors: Murphy, Keith, Dorfman, Scott, Law, Richard Jin, Le, Vivian Anne
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Nguyen, Nghi V
• Application Number:
  US15/299,112
• Publication Number:
  US 20170037349A1
• Time in Patent Office: 810 Days
• Field of Search: None
• CPC Class Codes: B29C 64/112 using individual droplets, e.g. from jetting heads
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 30/00 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B41J 3/407 for marking on special material
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 29/00 Means for introduction, extraction or recirculation of materials, e.g. pumps pumps per se F04B
• CPC Class Codes: C12M 33/00 Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture

Abstract

Described herein are bioprinters comprising: one or more printer heads, wherein a printer head comprises a means for receiving and holding at least one cartridge, and wherein said cartridge comprises contents selected from one or more of: bio-ink, and support material; a UV light module for optionally exposing the contents of at least one cartridge to UV light; a means for calibrating the position of at least one cartridge; and a means for dispensing the contents of at least one cartridge. Also described herein are methods of using and bioprinting cartridges for such bioprinters.

Claims

1. A method of fabricating a tissue construct comprising:

(a) depositing bio-ink onto a support with a bioprinter comprising;

(i) one or more printer heads, wherein a printer head comprises a means for receiving and holding at least one cartridge, wherein said cartridge comprises a bio-ink, and wherein the bio-ink comprises a solid or semi-solid composition of living cells;

(ii) a UV light module comprising a chamber for exposing the contents of at least one cartridge to UV light, wherein the at least one cartridge is receivable in the chamber and wherein the UV light module is configured to expose the contents of the at least one cartridge to UV light in the chamber prior to or during dispensing of the bio-ink; and

(iii) a means for dispensing the contents of at least one cartridge;

wherein the bio-ink comprises a UV cross-linkable material and is exposed to UV light to partially or completely cross-link the UV cross-linkable material to form a semi-solid or solid body; and

(b) incubating the bio-ink to allow it to cohere and to form a tissue, wherein said incubation has a duration of about 1 hour to about 10 days.

2. The method of claim 1, further comprising preparing a liquid bio-ink solution comprising a UV cross-linkable material and cells.

3. The method of claim 1, further comprising depositing bio-ink onto a support, wherein the bio-ink comprises a UV cross-linkable material and has not been exposed to UV light.

4. The method of claim 1, wherein the UV cross-linkable material is a hydrogel.

5. The method of claim 1, wherein the bio-ink comprises mammalian cells.

6. The method of claim 5, wherein the bio-ink comprises differentiated, mammalian cells.

7. The method of claim 5, wherein the bio-ink comprises non-differentiated, mammalian cells.

8. The method of claim 1, wherein the means for dispensing in (a)(iii) is by extrusion.

9. The method of claim 1, wherein the at least one cartridge in (a)(i) is a syringe or needle.

10. The method of claim 1, wherein the contents of the cartridge in (a)(i) further comprise an extrusion compound.

11. The method of claim 10, wherein the extrusion compound is collagen.