Biomimetic double network hydrogels

Patent metadata

Field	Value
Publication number	US-11840705-B2
Application number	US-201816607824-A
Country	US
Kind code	B2
Filing date	Apr 23, 2018
Priority date	Apr 24, 2017
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

Abstract

A double network hydrogel including a polymer (A) having a persistence length between 10 and 1000 nm; a flexible polymer (B), wherein the persistence length is measured according to single molecule force microscopy measurement, wherein polymer (B) has an extended coil conformation at a first condition and a collapsed globular conformation at a second condition. Polymer (A) preferably is a polyisocyanate, while polymer (B) is a crosslinked flexible polymer like for example PNIPAM. A method for making a double network hydrogel.

First claim

What is claimed is:

1. A double network hydrogel comprising:
a. a polymer (A) having a persistence length between 10 and 1000 nm,
b. a polymer (B) having a persistence length smaller than 1 nm,
wherein the persistence length is measured at room temperature in an aqueous solution at neutral pH according to single molecule force microscopy measurement,
wherein polymer (B) has an extended coil conformation at a first condition and a collapsed globular conformation at a second condition,
wherein the concentration of polymer (B) ranges between 1 and 80 mg/mL,
wherein the polymer (B) is a temperature responsive (thermoresponsive) polymer having a lower critical solution temperature (LCSTb), whereby the first condition is present at a temperature below LCSTb and the second condition is present at a temperature above the LCSTb,
wherein the polymer (A) has a lower critical solution temperature (LCSTa),
wherein the LCSTb is higher than the LCSTa, and
wherein the LCSTa is between 5° C. and 20° C.

2. The double network hydrogel according to claim 1 , wherein polymer (A) is selected from polyisocyanopeptides, DNA, actin, fibrin, intermediate filaments, collagen and cellulose derivatives.

3. The double network hydrogel according to claim 1 , wherein polymer (A) is an oligo(alkylene glycol)functionalized poly(isocyanopeptide).

4. The double network hydrogel according to claim 3 , wherein polymer (A) is a polymer based on the polymerization of isocyanopeptides which are functionalized with at least 3 ethylene glycol units.

5. The double network hydrogel according to claim 2 , wherein the polyisocyanopeptides (PIC) are present at a concentration between 0.25 mg/ml and 3.0 mg/ml.

6. The double network hydrogel according to claim 1 , wherein the viscosity average molecular weight of polymer (A) ranges between 200 and 1000 kg/mol (kDalton).

7. The double network hydrogel according to claim 1 , wherein polymer (B) is PNIPAM crosslinked with a multifunctional acrylate.

8. The double network hydrogel according to claim 7 , wherein the concentration of PNIPAM ranges between 3 and 80 mg/I.

9. A double network hydrogel according to claim 1 , wherein polymer (B) is selected from poly(acrylic acid) (PAAc) or poly(2-(dimethylamino)ethylethyl acrylate) (PDMA), copolymerized with acrylamide.

10. A process for making the double network hydrogel according to claim 1 , comprising the steps of:
a. providing an aqueous solution of polymer (A) at a temperature below a lower critical solution temperature of polymer (A) (LCSTa);
b. providing monomers B to be polymerized to polymer (B) having a LCSTb;
c. mixing the aqueous solution of polymer (A) with monomers (B) and subsequently heating the mixture to a temperature above the LCSTa and below the LCSTb to provide a hydrogel comprising polymer (A) and monomers (B);
d. inducing polymerization of monomers (B) at a temperature above the LCSTa and below the LCSTb to provide a double network hydrogel;
e. wherein polymer (A) is a polymer as defined above in claim 1 and
f. wherein polymer (B) is a polymer as defined above in claim 1 .

11. A method of using a hydrogel, comprising the step of: culturing cells with the double network hydrogel of claim 1 .

12. A coating, comprising: the double network hydrogel according to claim 1 .

13. The double network hydrogel according to claim 5 , wherein the polyisocyanopeptides (PIC) have the LCSTa between 10° C. and 20° C.

14. The double network hydrogel according to claim 6 , wherein the viscosity average molecular weight of polymer (A) ranges between 250 and 700 kg/mol.

15. The double network hydrogel according to claim 7 , wherein polymer (B) is PNIPAM crosslinked with N,N′-methylenebisacrylamide (MBAA).

16. The double network hydrogel according to claim 9 , wherein polymer (B) is PAAc with acrylamide, crosslinked with N,N′-methylenebisacrylamide (MBAA), wherein the concentration of polymer (B) ranges between 3 and 30 mg/mL, and wherein the LCSTb is at least 2° C. higher than the LCSTa.

17. The double network hydrogel according to claim 1 , wherein the LCSTb is at least 2° C. higher than the LCSTa.

18. The double network hydrogel according to claim 17 , wherein the LCSTb ranges between 20° C. and 40° C., and is at least 4° C. higher than the LCSTa.

Assignees

• Stichting Katholieke Univ
• Stichting Radboud Univ

Inventors

• Kouwer Paul
• Rowan Alan
• Jaspers Maarten
• De Almeida Paula

Classifications

• C12N5/0018 Primary

  Culture media for cell or tissue culture (media for specific animal cell type C12N5/06) · CPC title

• C08F120/54

  Amides {, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide} · CPC title

• C08J3/246 Primary

  Intercrosslinking of at least two polymers · CPC title

• C09D133/26

  Homopolymers or copolymers of acrylamide or methacrylamide · CPC title

• C08J2333/02

  Homopolymers or copolymers of acids; Metal or ammonium salts thereof · CPC title