Interpenetrating polymer network hydrogel

Patent metadata

Field	Value
Publication number	US-11759549-B2
Application number	US-201816107708-A
Country	US
Kind code	B2
Filing date	Aug 21, 2018
Priority date	Aug 21, 2017
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

An interpenetrating polymer network (IPN) structured hydrogel includes a crosslinked first natural polymer macromer with a first elasticity and an interpenetrating network of crosslinked second natural polymer macromers having a second elasticity higher than the first elasticity, the IPN structured hydrogel being cytocompatible, and, upon degradation, produce substantially non-toxic products.

First claim

Having described the invention, I claim:

1. A composition comprising:
a triple-network hydrogel having three types of crosslinking networks that includes crosslinked first natural polymer macromers with a first elasticity and a homogenously distributed interpenetrating network of crosslinked second natural polymer macromers having a second elasticity higher than the first elasticity, the triple-network hydrogel being cytocompatible, and, upon degradation, produce substantially non-toxic products,
wherein the first polymer macromers are oxidized alginates and the second polymer macromers are acrylated and/or methacrylated gelatin macromers, wherein the first natural polymer macromers are crosslinked with a first agent to form a first crosslinking network, and the second natural polymer macromer are crosslinked with a second agent different than the first agent to form a second crosslinking network, wherein the first agent crosslinks the first natural polymer macromers but not the second natural polymer macromers, and the second agent crosslinks the second natural polymer macromers but not the first natural polymer macromers, and wherein aldehyde groups of the oxidized acrylates form imine-bonds with amine groups of the acrylated and/or methacrylated gelatin macromers to form a third crosslinking network,
and wherein a plurality of cells are encapsulated within the hydrogel and mechanical stimulation of the hydrogel enhances cell proliferation and differentiation.

2. The composition of claim 1 , wherein the elasticity of the hydrogel is substantially maintained during degradation.

3. The composition of claim 1 , wherein the first natural polymer macromers are ionically crosslinkable with the first agent.

4. The composition of claim 1 , wherein the second natural polymer macromers are photocrosslinkable with the second agent.

5. The composition of claim 1 , further comprising at least one bioactive agent.

6. The composition of claim 1 , wherein the cells comprise progenitor cells, undifferentiated cells and/or differentiated cells.

7. The composition of claim 6 , wherein the cells include mesenchymal stem cells.

8. A composition comprising:
a triple-network hydrogel having three types of crosslinking networks that includes a crosslinked first natural polymer macromers with a first elasticity and a homogenously distributed interpenetrating network of crosslinked second natural polymer macromers having a second elasticity higher than the first elasticity, the triple-network hydrogel being cytocompatible, and, upon degradation, produce substantially non-toxic products, wherein the elasticity of the hydrogel is substantially maintained during degradation,
wherein the first polymer macromers are oxidized alginates and the second polymer macromers are acrylated and/or methacrylated gelatin macromers, wherein the first natural polymer macromers are crosslinked with a first agent to form a first crosslinking network and the second natural polymer macromer are crosslinked with a second agent different than the first agent to form a second crosslinking network, wherein the first agent crosslinks the first natural polymer macromers but not the second natural polymer macromers, and the second agent crosslinks the second natural polymer macromers but not the first natural polymer macromers, and wherein aldehyde groups of the oxidized acrylates form imine-bonds with amine groups of the acrylated and/or methacrylated gelatin macromers to form a third crosslinking network,
and wherein a plurality of cells are encapsulated within the hydrogel and mechanical stimulation of the hydrogel enhances cell proliferation and differentiation.

9. The composition of claim 8 , wherein the first natural polymer macromers are ionically crosslinkable with the first agent.

10. The composition of claim 8 , wherein the second natural polymer macromers are photocrosslinkable with the second agent.

11. The composition of claim 8 , further comprising at least one bioactive agent.

Assignees

• Univ Case Western Reserve

Inventors

• Alsberg Eben

Classifications

• A61L27/52 Primary

  Hydrogels or hydrocolloids · CPC title

• A61L27/44 Primary

  having a macromolecular matrix · 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

• C08H1/06

  derived from horn, hoofs, hair, skin or leather · 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