Bioink compositions and methods of preparing and using the same

Patent metadata

Field	Value
Publication number	US-2019106673-A1
Application number	US-201816156535-A
Country	US
Kind code	A1
Filing date	Oct 10, 2018
Priority date	Oct 11, 2017
Publication date	Apr 11, 2019
Grant date	—

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 (e.g., methacrylated Type 1 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, 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

• C12N2533/54

  Collagen; Gelatin · CPC title

• A61L27/38

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

• C12N2533/80

  Hyaluronan · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• C12N2513/00

  3D culture · CPC title