Viscoelastic hydrogel regulation of organoid patterning and vascularization

Patent metadata

Field	Value
Publication number	US-2026086082-A1
Application number	US-202519175444-A
Country	US
Kind code	A1
Filing date	Apr 10, 2025
Priority date	Sep 20, 2024
Publication date	Mar 26, 2026
Grant date	—

Abstract

A spinal cord model and methods of making and using the same.

First claim

What is claimed is:

1 . A method of screening a therapeutic agent, the method comprising:
a) culturing a plurality of induced pluripotent stem cells on a cell scaffold to form a spinal cord spheroid or organoid or a fragment thereof, the cell scaffold comprising methacrylated hyaluronic acid (HAMA) and dopamine-modified hyaluronic acid (HA-Cat); and b) administering the therapeutic agent to the spinal cord spheroid or organoid or fragment thereof.

2 . The method of claim 1 , wherein the induced pluripotent stem cells comprise healthy cells.

3 . The method of claim 1 , wherein the induced pluripotent stem cells comprise diseased or abnormal cells.

4 . The method of claim 1 , wherein the induced pluripotent stem cells are human.

5 . The method of claim 1 , wherein the therapeutic agent is targeted to treat and/or prevent a neurodevelopmental disorder, a neurodegenerative disease or disorder, a neurological disease or disorder, brain cancer, or spinal cancer.

6 . The method of claim 1 , wherein the cell scaffold comprises:
up to about 2 wt % HAMA; and up to about 2 wt % HA-Cat.

7 . The method of claim 1 , wherein:
the HAMA has a molecular weight of from about 50 kDa to about 2000 kDa; and the HA-Cat has a molecular weight of from about 50 kDa to about 2000 kDa.

8 . The method of claim 1 , wherein the cell scaffold further comprises a crosslinker comprising:
up to about 1 wt % 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (NHS); and up to about 2 wt % thiolated polyethylene glycol (PEG).

9 . The method of claim 1 , wherein the cell scaffold further comprises from about 5 mM to about 15 mM Fe 3+ .

10 . The method of claim 1 , wherein the cell scaffold has a damping factor (tan δ) of from about 0.03 to about 0.3.

11 . The method of claim 1 , wherein the cell scaffold has a compression modulus (E) of from about 250 Pa to about 10,000 Pa.

12 . The method of claim 1 , wherein the cell scaffold has a stress relaxation time of from about 10 seconds to about 1000 seconds.

13 . The method of claim 1 , wherein:
the one or more ventral markers comprise SOX2, FOXA2, LHX3, NKX2.2, and/or OLIG2; the one or more dorsal markers comprise PAX7, LHX3, LMX1, LHX9, and/or BRN3; and the one or more interneuron markers comprise DBX1, DBX2, and or PAX6.

14 . The method of claim 1 , wherein, compared to a reference spinal cord spheroid or organoid or fragment thereof not cultured on the cell scaffold, the spinal cord spheroid or organoid or fragment thereof comprises:
at least about 1.5-fold greater expression of the one or more ventral markers; at least about 2-fold greater expression of the one or more dorsal markers; and/or at least about 2-fold greater expression of the one or more interneuron markers.

Assignees

• Univ Florida State Res Found Inc

Inventors

• Zeng Changchun
• Li Yan
• Chen Xingchi

Classifications

• C12N5/0618

  Cells of the nervous system · CPC title

• C12N2537/10

  Cross-linking · CPC title

• C12N2513/00

  3D culture · CPC title

• C12N5/0691 Primary

  Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels · CPC title

• C12N2533/40

  Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers · CPC title