Dynamic covalent hydrogels, precursors thereof and uses thereof

1 . A crosslinking pair of hydrogel precursor polymers comprising:

(1) a first hydrogel precursor polymer consisting of a first polymer modified with a Wulff-type phenylboronic acid, and

(2) a second hydrogel precursor polymer consisting of a second polymer modified with glucamine.

2 . The crosslinking pair of hydrogel precursor polymers according to claim 1 , wherein the first polymer is grafted with the Wulff-type phenylboronic acid and the second polymer is grafted with glucamine.

3 . The crosslinking pair of hydrogel precursor polymers according to claim 1 , wherein the first and second polymers are independently selected from natural polymers, semi-synthetic polymers, and synthetic polymers.

4 . The crosslinking pair of hydrogel precursor polymers according to claim 3 , wherein at least one of the first and second polymers is selected from biocompatible, biodegradable, hydrophilic natural polymers, semi-synthetic polymers, and synthetic polymers.

5 . The crosslinking pair of hydrogel precursor polymers according to claim 1 , wherein the first hydrogel precursor polymer or the second hydrogel precursor polymer is directly or indirectly covalently linked to a bioorthogonal functional moiety or to a clickable moiety.

6 . The crosslinking pair of hydrogel precursor polymers according to claim 1 , wherein the first hydrogel precursor polymer is in a first aqueous solution; and the second hydrogel precursor polymer is in a second aqueous solution, the first and second aqueous solutions being separate aqueous solutions.

7 . The crosslinking pair of hydrogel precursor polymers according to claim 6 , wherein at least one of the first and second aqueous solutions comprises a component selected from the group consisting of cells, bioactive agents, visualization agents, and any combination thereof.

8 . A dynamic covalent hydrogel composed of a first hydrogel precursor polymer and a second hydrogel precursor polymer of a crosslinking pair as defined in claim 1 , wherein the first and second hydrogel precursors are crosslinked by dynamic covalent bonds.

9 . A dynamic covalent hydrogel according to claim 8 further comprising a component selected from the group consisting of cells, bioactive agents, visualization agents, and any combination thereof.

10 . A pharmaceutical composition comprising a crosslinking pair of hydrogel precursor polymers according to claim 1 , and at least one pharmaceutically acceptable carrier or excipient.

11 . A pharmaceutical composition comprising a dynamic covalent hydrogel according to claim 8 , and at least one pharmaceutically acceptable carrier or excipient.

12 . The pharmaceutical composition according to claim 10 , wherein the first hydrogel precursor polymer and the second precursor hydrogel polymer are contained in a multi-barrel syringe.

13 . A kit comprising a crosslinking pair of hydrogel precursor polymers according to claim 1 , and instructions to use the crosslinking pair.

14 . A kit comprising a dynamic covalent hydrogel according to claim 8 , and instructions to use the dynamic covalent hydrogel.

15 . A kit comprising a pharmaceutical composition according to claim 10 , and instructions to use the pharmaceutical composition.

16 . A method for preparing a dynamic covalent hydrogel comprising a step of mixing a first hydrogel precursor polymer and a second hydrogel precursor polymer of a crosslinking pair as defined in claim 1 to obtain a dynamic covalent hydrogel.

17 . A method according to claim 16 , wherein said method is carried out under physiological conditions.

18 . The crosslinking pair of hydrogel precursor polymers according to claim 1 , wherein the Wulff-type phenylboronic acid has formula (II):

wherein R and R′ are independently selected from hydrogen, substituted or unsubstituted C 1 -C 20 alkyls, substituted or unsubstituted C 1 -C 10 alkenyls, substituted or unsubstituted C 1 -C 10 alkynyls, acyls-C(═O) R 1a , wherein R 1a is a substituted or unsubstituted C 1 -C 20 alkyl group) and carboxy groups-C(═O) OR 1b , wherein R 1b is a substituted or unsubstituted C 1 -C 20 alkyl group,

wherein substituted alkyls, alkenyls and alkynyls are substituted with one or more substituents selected from halogen (F, Br, I, Cl), hydroxy (—OH), amino (—NR 2 R 3 , wherein R 2 and R 3 are independently selected from hydrogen and substituted or unsubstituted C 1 -C 20 alkyl), alkoxy (—OR 1c , wherein Ric is a substituted or unsubstituted C 1 -C 20 alkyl group), carboxy (—C(═O) OR 1b , wherein R 1b is a substituted or unsubstituted C 1 -C 20 alkyl group), amido (—NR 2 C(═O) R 3 or —C(═O) NR 2 R 3 , wherein R 2 and R 3 are independently selected from hydrogen and substituted or unsubstituted C 1 -C 20 alkyl), nitro (—NO 2 ), oxo (═O), and cyano (—CN) groups.

19 . The crosslinking pair of hydrogel precursor polymers according to claim 18 , wherein the Wulff-type phenylboronic acid is 2-((dimethylamino) methyl)-phenylboronic acid.

20 . The crosslinking pair of hydrogel precursor polymers according to claim 18 , wherein the Wulff-type phenylboronic acid is (2-(((4-aminobutyl) amino)-methyl) phenyl) boronic acid.

21 . A method for delivering cells and/or bioactive agents to a subject, said method comprising a step of using a crosslinking pair of hydrogel precursor polymers according to claim 1 for delivering said cells and/or bioactive agent to said subject.

22 . A method of viscosupplementation in a subject, said method comprising a step of injecting a crosslinking pair of hydrogel precursor polymers according to claim 1 in at least one joint in said subject.

23 . A method of regenerative medicine in a subject, said method comprising steps of (a) using a crosslinking pair of hydrogel precursor polymers according to claim 1 to produce a tissue equivalent and (b) implanting the tissue equivalent obtained in step (a) into said subject.