Bioink compositions and methods of preparing and using the same

Patent metadata

Field	Value
Publication number	US-11629329-B2
Application number	US-201816156535-A
Country	US
Kind code	B2
Filing date	Oct 10, 2018
Priority date	Oct 11, 2017
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

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.

First claim

That which is claimed is:

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.

Assignees

• Univ Wake Forest Health Sciences

Inventors

• Skardal Aleksander

Classifications

• C12N2513/00

  3D culture · CPC title

• B33Y70/00 Primary

  Materials specially adapted for additive manufacturing · CPC title

• C12N2533/80

  Hyaluronan · CPC title

• A61L2300/414

  Growth factors · CPC title

• A61L27/38

  containing added animal cells (organs or tissue containing native cells A61L27/36) · CPC title