Catechol group modified biomacromolecular scaffold material and preparation method thereof

Patent metadata

Field	Value
Publication number	US-11384162-B2
Application number	US-201716071027-A
Country	US
Kind code	B2
Filing date	Aug 31, 2017
Priority date	Sep 7, 2016
Publication date	Jul 12, 2022
Grant date	Jul 12, 2022

Abstract

The invention discloses a preparation method of a catechol group modified biomacromolecular scaffold material, comprising: grafting a catechol-containing compound by amidation to obtain modified biomacromolecules; then, allowing dopamine to perform oxidized self-polymerization in a weakly alkaline buffer solution to form polydopamine (PDA) particles with a uniform particle size; next, forming a scaffold which has three cross-linking structures, namely modified biomacromolecules, modified biomacromolecules/PDA, and biomacromolecules/PDA, through interaction between catechol groups, interaction between catechol groups and PDA particles, and interaction between macromolecules and PDA particles in the modified macromolecules respectively; and cross-linking the scaffold with calcium ions, adipic dihydrazide or genipin to further adjust the degree of cross-linking and porosity of the scaffold. The prepared scaffold material has excellent biocompatibility and biodegradability, can promote cell adhesion, and has a wide application prospect in the field of tissue repair and regeneration.

First claim

What is claimed is:

1. A method of making a catechol group modified biomacromolecular scaffold material wherein dopamine is taken as a functional group to physically or chemically modify biomacromolecules with a compound containing the catechol group, wherein the biomacromolecules are selected from the group consisting of alginic acid, hyaluronic acid, polyglutamic acid, chitosan, polylysine, and combinations thereof.

2. The method according to claim 1 wherein the modifying comprises:
1) subjecting the compound containing catechol groups and the biomacromolecules to amidation to obtain modified biomacromolecules;
2) generating polydopamine particles by self-polymerization of dopamine in an aqueous solution of ammonia;
3) forming a scaffold having three cross-linking structures of modified biomacromolecules, modified biomacromolecules/polydopamine, and biomacromolecules/polydopamine through interaction between the catechol groups, interaction between the catechol groups and the polydopamine particles, and interaction between the biomacromolecules and the polydopamine particles; and
3) further cross-linking the scaffold of step 2) with calcium ions to obtain a gradient scaffold material.

3. The method according to claim 1 wherein when the biomacromolecules are alginic acid, hyaluronic acid or polyglutamic acid, the compound containing the catechol group is dopamine; and when biomacromolecules are chitosan or polylysine, the compound containing the catechol group is 3,4-dihydroxyphenylpropionic acid.

4. The method according to claim 1 wherein the feeding ratio of the biomolecules to the compound containing the catechol group is within the range of 2:1-1:5, and the degree of substitution of the catechol group in the biomolecules is within the range of 16-60%.

5. The method according to claim 2 wherein during the preparation process of the polydopamine particles, the amount of ammonia water is within the range of 0.5-3.5 mL, and the particle size of the obtained polydopamine particles is within the range of 150-560 nm.

6. The method according to claim 2 wherein the concentration of the calcium ions is 5%.

7. The method according to claim 2 wherein the porosity of the gradient scaffold material is within the range of 88-91%.

8. A method of making a catechol group modified biomacromolecular scaffold material comprising:
I.
1) reacting biomacromolecules with a compound containing catechol groups to perform amidation and obtain catechol group modified biomacromolecules;
2)
a) freeze-drying the catechol group modified biomacromolecules of step 1) to obtain a freeze-dried catechol group modified biomacromolecular material; or, in the alternative,
b) mixing the catechol group modified biomacromolecules of step 1) with polydopamine to obtain a mixture of the catechol group modified biomacromolecules and polydopamine and then freeze-drying the mixture of the catechol group modified biomacromolecules and polydopamine to obtain a catechol group modified biomacromolecules/polydopamine compound material; and

3) cross-linking the freeze-dried catechol group modified biomacromolecular material of step 2.a) or the catechol group modified biomacromolecules/polydopamine compound material of step 2.b) with a cross-linking agent to obtain the catechol group modified biomacromolecular compound scaffold material.

9. The method according to claim 8 wherein the biomacromolecules are selected from the group consisting of alginic acid, hyaluronic acid, polyglutamic acid, chitosan, polylysine, and combinations thereof.

10. The method according to claim 9 wherein when the biomacromolecules are alginic acid, the cross-linking agent is calcium salt;
when the biomacromolecules are hyaluronic acid or polyglutamic acid, the cross-linking agent is adipic dihydrazide;
and when the biomacromolecules are chitosan or polylysine, the cross-linking agent is genipin.

11. The method according to claim 8 further comprising forming the polydopamine by oxidized polymerization of dopamine.

12. The method according to claim 8 wherein the compound containing the catechol groups is dopamine or 3,4-dihydroxyphenylpropionic acid.

13. The method according to claim 12 wherein when the biomacromolecules are alginic acid, hyaluronic acid or polyglutamic acid, the compound containing the catechol groups is dopamine;
and when the biomacromolecules are chitosan or polylysine, the compound containing the catechol groups is 3,4-dihydroxyphenylpropionic acid.

14. The method according to claim 8 wherein the feeding ratio of the biomolecules to the compound containing the catechol groups is within the range of 2:1-1:5.

15. The method according to claim 8 wherein the degree of substitution of the catechol groups in the biomolecules is within the range of 16-60%.

16. The method according to claim 8 wherein the porosity of the catechol group modified biomacromolecular scaffold material is within the range of 88-91%.

17. A method of making a catechol group modified biomacromolecular scaffold material comprising:
1) mixing biomacromolecules with polydopamine to obtain a mixture of the biomacromolecules with the polydopamine,
2) freeze-drying the mixture of the biomacromolecules and polydopamine of step 1) to obtain a freeze-dried biomacromolecules/polydopamine compound material; and
3) cross-linking the freeze-dried biomacromolecules/polydopamine compound material of 2) with a cross-linking agent to obtain the catechol group modified biomacromolecular scaffold material.

Assignees

• Univ Jiangnan

Inventors

• Shi Dongjian
• Shen Jiali
• Zhang Zhuying
• Cao Chuanhao
• Zhao Qian
• Li Xiaojie
• Chen Mingqing

Classifications

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L27/26

  Mixtures of macromolecular compounds · CPC title

• C08B37/0072

  Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates · CPC title

• C08G69/10

  Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)} · CPC title