Injectable tough and viscoelastic bta hydrogel

Patent metadata

Field	Value
Publication number	US-2025058024-A1
Application number	US-202218706336-A
Country	US
Kind code	A1
Filing date	Nov 1, 2022
Priority date	Nov 1, 2021
Publication date	Feb 20, 2025
Grant date	—

Abstract

The invention describes benzene-1,3,5-tricarboxamide (BTA) based hydrogels. The hydrogels have purpose in tissue culturing for in vitro applications such as drug screening or in vivo applications such as transplantation. The hydrogels are particularly tough but still allow 3D printing and cell culturing. The invention further describes 3D printing of the hydrogels and uses of the hydrogels.

First claim

1 . A compound having the formula represented by formula (Ia):

wherein:
each 1, m, and n are individually an integer between 1 to 18; and
R 1 , R 2 and R 3 are each individually selected from a polymer or a reactive group,
wherein
the polymer is represented by

R 4
wherein

represents

polyester co-polymers, polysaccharides, polyacrylates, polyacrylamides, polyurethanes or co-polymers thereof, wherein m is an integer from 1 to 20000 and
wherein R 4 is a natural chain end or a reactive group, and
wherein the polymer is selected such that the compound is water soluble or water dispersible; and
wherein the reactive group is selected from the group consisting of:
a C 1 -C 36 linear or branched alkyl or alkenyl or alkynyl or cycloalkyl,

azides, alkynes, amines, oximes, hydrazides, semicarbazides, aldehydes, strained triple bonds, epoxides, malimides, furans or substitutions thereof, preferably substitutions with a linear or branched alkyl group, acrylate or acrylamide or sulphides thereof, and
wherein at least one of R 1 , R 2 or R 3 is a polymer.

2 . The compound of claim 1 , wherein the compound represented by formula (IVa) or formula (IVb):

wherein X 1 and X 2 are each individually selected from:

polyester co-polymers, polysaccharides, polyacrylates, polyacrylamides, polyurethanes or co-polymers thereof, wherein o and p are individually an integer from 1 to 20000,
and wherein R 5 and R 6 are each individually selected from H, OH, NH 2 , a C 1 -C 36 linear or branched alkyl or alkenyl or alkynyl or cycloalkyl,

azides, alkynes, amines, oximes, hydrazides, semicarbazides, aldehydes, strained triple bonds, epoxides, malimides, furans or substitutions thereof or

3 . The compound of claim 1 , wherein the compound is represented by formula (Ib):

wherein:
each a is individually an integer between 1 to 18;
each n is individually an integer between 6 to 18;
wherein

represents

polyester co-polymers, polysaccharides, or co-polymers thereof, wherein m is an integer from 1 to 20000; and
each R is individually selected from the group consisting of:
a C 1 -C 36 linear or branched alkyl or alkenyl or alkynyl or cycloalkyl,

or
substitutions thereof, preferably substitutions with a linear or branched alkyl group, acrylate or acrylamide or sulphides thereof,
with the proviso that at least two, preferably at least three, more preferably all four, R are individually selected form the group consisting of:

or
substitutions thereof, preferably substitutions with a linear or branched alkyl group, acrylate or acrylamide or sulphides thereof.

4 . The compound according to claim 1 , wherein the compound is represented by formula (IIa) or (IIb):

wherein:
each n is individually an integer between 6 to 18; and
m is an integer from 1 to 20000;

wherein:
each n is individually an integer between 6 to 18; and
m is an integer from 1 to 20000.

5 . The compound of claim 1 , wherein the compound is further modified with the covalent attachment of one or more peptides, antibodies, growth factors, DNA strands, glycans or combinations thereof.

6 . A hydrogel comprising the compound according to claim 1 .

7 . The hydrogel according to claim 6 , further comprising a cross-linking agent,
wherein the crosslinking agent is a compound comprising two or more reactive groups each individually selected from the group consisting of azide, alkyne, amine, oxime, hydrazide, thiol, furan, malimide, acrylate, amine and derivatives thereof, preferably wherein the crosslinker is defined as:

wherein

represents

polyester co-polymers, polysaccharides, polyacrylates, polyacrylamides, polyurethanes or co-polymers thereof, wherein m is an integer from 1 to 20000, and wherein each Y is individually selected from an azide, alkyne, amine, oxime, hydrazide, thiol, furan, malimide, acrylate, amine or a derivative thereof, or
wherein the crosslinking agent is represented by formula (IIIa), formula (IIIb), formula (IIIc), formula (IIId):

wherein a is an integer ranging from 0 to 12;

wherein b is an integer ranging from 0 to 10000;

wherein each c is individually an integer ranging from 0 to 250; or

wherein

represents a peptide of 2 to 45 amino acids, preferably an enzymatically cleavable peptide; or

wherein f is an integer ranging from 1 to 10 and wherein each g is individually an integer ranging from 0 to 250
and wherein in the formulas IIIa, IIIb, IIIc, IIId and IIIe each Y individually is selected from an azide, alkyne, amine, oxime, hydrazide, thiol, furan, malimide, acrylate, amine or a derivative thereof.

8 . The hydrogel according to claim 6 comprising between 0.25 to 30 w/v %, preferably between 1 and 10 w/v %, of the compound.

9 . The hydrogel according to claim 6 , wherein the molar ratio of the compound to cross-linking agent is between 10:1 and 1:4.

10 . The hydrogel according to c

Assignees

• Univ Maastricht
• Acad Ziekenhuis Maastricht

Inventors

• Baker Matthew Brandon
• Hafeez Shahzad
• Moroni Lorenzo
• Aldana Ana Agustina

Classifications

• C08G65/00

  Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule · CPC title

• C07D207/46

  with hetero atoms directly attached to the ring nitrogen atom · CPC title

• C07C205/57

  having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton · CPC title

• C07C69/76

  Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring · CPC title

• A61L27/38

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