Hydrogels with dynamically adjustable mechanical properties

Patent metadata

Field	Value
Publication number	US-11116875-B2
Application number	US-201816107774-A
Country	US
Kind code	B2
Filing date	Aug 21, 2018
Priority date	Aug 21, 2017
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

A composition includes a dual crosslinkable hydrogel that includes a plurality of polymer macromers, which are crosslinked with a first agent and a second agent different than the first agent, wherein the crosslinks formed using the second agent are reversible and repeatable to allow the mechanical properties of the hydrogel to be dynamically adjusted.

First claim

Having described the invention, we claim:

1. A method of regulating cell behavior, the method comprising:
providing a dual crosslinkable hydrogel that includes a plurality of polymer macromers that are crosslinked with a first agent and a second agent different than the first agent and a plurality of cells dispersed in the crosslinked polymer macromers, the crosslinks formed using the second agent being reversible and repeatable to allow the mechanical properties of the hydrogel to be dynamically adjusted, and
dynamically adjusting the mechanical properties of the dual crosslinkable hydrogel by increasing or decreasing crosslinking with the second agent to modulate the growth and/or proliferation of the cells within the hydrogel.

2. The method of claim 1 , wherein the stiffness of the hydrogel is dynamically adjusted by increasing or decreasing crosslinking with the second agent.

3. The method of claim 1 , wherein an increase of the crosslinks formed using the second agent increases the stiffness of the hydrogel and a decrease in the crosslinks formed using the second agent decreases the stiffness of the hydrogel.

4. The method of claim 1 , wherein the hydrogel further comprises at least one bioactive agent.

5. The method of claim 4 , wherein release of the bioactive agent from the hydrogel is controlled by dynamically adjusting the mechanical properties of the hydrogel.

6. The method of claim 1 , wherein the polymer macromers comprise biodegradable acrylated and/or methacrylated natural polymer macromers.

7. The method of claim 6 , wherein the acrylated and/or methacrylated, natural polymer macromers are polysaccharides, which are optionally oxidized.

8. The method of claim 6 , the natural polymer macromers comprising oxidized, acrylated and/or methacrylated alginates.

9. The method of claim 1 , wherein the polymer macromers are photocrosslinked with the first agent.

10. The method of claim 1 , wherein the polymer macromers are ionically crosslinked with the second agent.

11. The method of claim 10 , wherein second agent comprises calcium ions.

Assignees

• Univ Case Western Reserve

Inventors

• Alsberg Eben
• Jeon Oju
• Kim Tae-Hee

Classifications

• A61L27/52 Primary

  Hydrogels or hydrocolloids · CPC title

• A61L2400/16

  Materials with shape-memory or superelastic properties · CPC title

• A61L27/3834

  Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells · CPC title

• C08B37/0084

  Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates · CPC title

• A61L27/54

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