IP Library Granted Patent US 11,629,329
Granted Patent B2
US 11,629,329 · App. 16/156,535 · Granted Apr 18, 2023

Bioink compositions and methods of preparing and using the same

Inventor: Aleksander Skardal (Clemmons, NC)
Assignee: Wake Forest University Health Sciences
C12N5/0062A61L27/26A61L27/38A61L27/50A61L27/52A61L27/54B33Y70/00A61L2300/414C12N2513/00C12N2533/54C12N2533/80
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Quick Facts
Patent No.
US 11,629,329
App. No.
16/156,535
Granted
Apr 18, 2023
Kind
B2
Abstract

Described herein are bioink compositions, which may have an elastic modulus similar to a natural tissue and/or tunable mechanical properties, along with methods of preparing and using the compositions. The compositions described herein may be useful as a medium for cell and/or tissue culture and/or for bioprinting, but are not limited thereto.

Claims (29)

1. A composition comprising:

thiolated hyaluronic acid;

methacrylated collagen; and

water.

2. The composition of claim 1 , wherein the thiolated hyaluronic acid is present in the composition in an amount of about 0.1% to about 2% w/v of the composition.

3. The composition of claim 1 , wherein the methacrylated collagen is present in the composition in an amount of about 0.5 mg/mL of the composition to about 10 mg/mL of the composition.

4. The composition of claim 1 , wherein the composition has a ratio of the thiolated hyaluronic acid to the methacrylated collagen in a range from 1:0.5 to 1:10 (thiolated hyaluronic acid:methacrylated collagen) by volume.

5. The composition of claim 1 , wherein the composition has a pH of about 6.5 or 7 to about 7.5 or 8.

6. The composition of claim 1 , wherein the composition is extrudable with an applied mechanical stress in a range from about 1 kPa to about 80 kPa.

7. The composition of claim 1 , wherein the composition comprises a greater number of methacrylate groups as compared to thiol groups.

8. The composition of claim 1 , further comprising one or more small molecule(s) comprising a functional group that provides hydrogen bonding.

9. The composition of claim 8 , wherein the one or more small molecule(s) comprises a catechol amine, a catechol containing an alkynyl imine, a catechol containing an alkynyl amine, a catechol containing an alkenyl imine, a catechol containing an alkenyl amine, a catechol containing an acrylate imine, a catechol containing an acrylate amine, a catechol containing a methacrylate imine, benzylamine, and/or a catechol containing a methacrylate amine.

10. The composition of claim 1 , further comprising a protein and/or proteoglycan.

11. The composition of claim 1 , further comprising fibronectin, heparin, and/or laminin.

12. The composition of claim 1 , further comprising one or more live cell(s).

13. The composition of claim 1 , wherein the composition has an elastic modulus from about 10 or 25 Pa to about 500 or 1,000 Pa.

14. The composition of claim 1 , further comprising one or more growth factor(s).

15. The composition of claim 1 , further comprising a thermal initiator or photoinitiator.

16. The composition of claim 1 , wherein the composition is thixotropic.

17. The composition of claim 6 , wherein the composition has an elastic modulus after extrusion that varies by less than about 20% compared to an elastic modulus of the composition prior to extrusion and/or the composition during extrusion has an elastic modulus G′ that is less than a loss modulus G″.

18. The composition of claim 6 , wherein the composition has an elastic modulus G′ and a loss modulus G″ that are within ±20% of each other.

19. A method of making an organoid, comprising:

providing a composition of claim 1 having a pH of about 6.5 or 7 to about 7.5 or 8;

adding one or more live cell(s) to the composition to provide a hyaluronic acid-collagen hydrogel including the cells; and

forming an organoid from the hyaluronic acid-collagen hydrogel.

20. A method of increasing the viability and/or functional activity of an organoid, the method comprising:

providing a composition of claim 1 comprising live cells to provide a hyaluronic acid-collagen hydrogel including cells;

forming an organoid from the hyaluronic acid-collagen hydrogel; and

culturing the cells in the organoid, thereby increasing the viability and/or functional activity of an organoid compared to an organoid in the absence of the hyaluronic acid-collagen hydrogel.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 10, 2022
From: WAKE FOREST UNIVERSITY HEALTH SCIENCES
To: UNITED STATES GOVERNMENT
Reel/Frame 061912/0666 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2019
From: SKARDAL, ALEKSANDER
To: WAKE FOREST UNIVERSITY HEALTH SCIENCES
Reel/Frame 048985/0468 →
Continuity (2)
Provisional Application 62570825 · Oct 11, 2017
Related Publication 20190106673A1 · Apr 11, 2019