IP Library › Granted Patent US 12,448,605
Granted Patent B2
US 12,448,605 · App. 17/808,873 · Granted Oct 21, 2025

Encapsulation and cardiac differentiation of hiPSCs in 3D PEG-fibrinogen hydrogels

Inventors: Elizabeth A. Lipke (Auburn, AL); Petra Kerscher (Auburn, AL); Alexander J. Hodge (Auburn, AL)
Assignee: Auburn University
C12N5/0657C12N5/0696C12N2500/46C12N2500/50C12N2501/999C12N2506/45C12N2513/00C12N2533/52C12N2533/54C12N2537/10
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Quick Facts
Patent No.
US 12,448,605
App. No.
17/808,873
Granted
Oct 21, 2025
Kind
B2
Abstract

The present invention relates to the production of cell cultures and tissues from undifferentiated pluripotent stem cells using three-dimensional biomimetic materials. The resultant cell cultures or tissues can be used in any of a number of protocols including testing chemicals, compounds, and drugs. Further, the methods and compositions of the present invention further provide viable cell sources and novel cell delivery platforms that allow for replacement of diseased tissue and engraftment of new cardiomyocytes from a readily available in vitro source. The present invention includes novel methods required for the successful production of cell cultures and tissues, systems and components used for the same, and methods of using the resultant cell and tissue compositions.

Claims (25)

1. A method of screening a candidate compound or substance for an effect on cardiac tissue, the method comprising:

forming a biomimetic-PSC suspension by suspending a population of pluripotent stem cells (PSCs) in a covalently crosslinkable component and a natural hydrogel component, the natural hydrogel component comprising one or more of fibrinogen, collagen, gelatin, hyaluronic acid, elastin, fibronectin, laminin, fibrin, alginate, and decellularized cardiac extracellular matrix;

crosslinking the biomimetic-PSC suspension to produce a three-dimensional biomimetic PSC microenvironment;

culturing the three-dimensional biomimetic-PSC microenvironment to differentiate the three-dimensional biomimetic-PSC microenvironment into a three-dimensional, synchronously contracting cardiac tissue;

exposing the cardiac tissue to a candidate compound or substance; and

determining an effect of the candidate compound or substance on the cardiac tissue.

2. The method of claim 1 , wherein determining an effect comprises determining a level of toxicity of the candidate compound or substance to the cardiac tissue.

3. The method of claim 1 , wherein determining an effect comprises determining a level of efficacy of the candidate compound or substance as a treatment.

4. The method of claim 1 , wherein the candidate compound or substance is thalidomide.

5. The method of claim 1 , wherein the candidate compound or substance is isoproterenol.

6. The method of claim 1 , further comprising predicting a triggering of cardiac arrhythmias.

7. The method of claim 1 , wherein crosslinking the biomimetic-PSC suspension comprises producing microislands.

8. The method of claim 1 , wherein crosslinking the biomimetic-PSC suspension comprises producing discs.

9. The method of claim 1 , wherein the cardiac tissue contracts spontaneously.

10. The method of claim 1 , wherein the cardiac tissue comprises mature ultrastructural features.

11. The method of claim 10 , wherein the cardiac tissue comprises T-tubules.

12. The method of claim 10 , wherein the cardiac tissue comprises sarcomeres spaced by 1.8 micrometers to 2.0 micrometers.

13. The method of claim 10 , wherein the cardiac tissue comprises axially aligned cardiomyocytes.

14. The method of claim 10 , wherein the cardiac tissue comprises H-bands.

15. The method of claim 10 , wherein the cardiac tissue comprises basement membrane with caveolae.

16. The method of claim 10 , wherein the cardiac tissue comprises intercalated discs and gap junctions.

17. The method of claim 1 , wherein the covalently crosslinkable component comprises an acrylate component.

18. The method of claim 17 , wherein the acrylate component comprises acrylated PEG.

19. The method of claim 17 , wherein the acrylate component comprises acrylated gelatin.

20. The method of claim 1 , wherein the method of screening is a high throughput method of screening.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 28, 2022
From: LIPKE, ELIZABETH A.; KERSCHER, PETRA; HODGE, ALEXANDER J.
To: AUBURN UNIVERSITY
Reel/Frame 060336/0244 →
Continuity (5)
Continuation 16420714 · May 23, 2019
Continuation 15411807 · Jan 20, 2017
Continuation 14538435 · Nov 11, 2014
Provisional Application 61902453 · Nov 11, 2013
Related Publication 20220403338A1 · Dec 22, 2022
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