Preparation method and application of sulfhydryl/disulfide bond controllable self-crosslinked hyaluronic acid hydrogel

A hyaluronic acid and hydrogel technology, applied in medical science, prosthesis, etc., can solve problems such as affecting the biocompatibility of hydrogel materials, and achieve good water solubility, controllable physical properties, and simple gelation method. Effect

Active Publication Date: 2015-09-09
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Carboxyl, hydroxyl, amino and other chemically active functional groups are often used in chemical crosslinking reactions. Commonly used chemical crosslinking agents generally contain bifunctional groups, such as diamine, dihydrazine, dialdehyde, diol, etc., but these crosslinking agents Agents are usually cytotoxic, if residual will affect the biocompatibility of hydrogel materials

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  • Preparation method and application of sulfhydryl/disulfide bond controllable self-crosslinked hyaluronic acid hydrogel
  • Preparation method and application of sulfhydryl/disulfide bond controllable self-crosslinked hyaluronic acid hydrogel
  • Preparation method and application of sulfhydryl/disulfide bond controllable self-crosslinked hyaluronic acid hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] (1) Dissolve 400mg of sodium hyaluronate in 100mL of deionized water, first add 230mg of N-succinimide (NHS), fully dissolve; then add 385mg of 1-ethyl-(3-dimethylaminopropyl) Carbodiimide hydrochloride (EDC·HCl) powder, adjust the pH=4.75 of the reaction solution with 1M NaOH and 1M HCl solution, and react for 2 hours; then add 10mL of 11.36mg / mL cysteine ​​( CSH·HCl) hydrochloride, react for 24 hours; finally adjust the pH of the reaction solution to 8.5 with 1M NaOH solution, add 10 mL of 46.5 mg / ml dithiothreitol (DTT) solution, and react for 12 hours.

[0064] (2) After the reaction, adjust the pH of the reaction solution to 3.0-3.5 with 1M HCl solution, dialyze in deionized water with pH=3.0-3.5 for 72 hours, and freeze-dry to obtain cysteine-modified hyaluronic acid.

[0065] Among them, the molecular weight of sodium hyaluronate is 0.1MDa, carboxyl group in sodium hyaluronate: N-succinimide: 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride: half The m...

Embodiment 2

[0069] (1) Dissolve 400mg of sodium hyaluronate in 100mL of deionized water, first add 230mg of N-succinimide (NHS), fully dissolve; then add 575mg of 1-ethyl-(3-dimethylaminopropyl) Carbodiimide hydrochloride (EDC·HCl) powder, adjust the pH=4.75 of the reaction solution with 1M NaOH and 1M HCl solution, and react for 2 hours; then add 10mL of 22.72mg / mL cysteine ​​( CSH·HCl) hydrochloride, react for 24 hours; finally adjust the pH of the reaction solution to 8.5 with 1M NaOH solution, add 10 mL of 93.0 mg / ml dithiothreitol (DTT) solution, and react for 12 hours.

[0070] (2) After the reaction, adjust the pH of the reaction solution to 3.0-3.5 with 1M HCl solution, dialyze in deionized water with pH=3.0-3.5 for 72 hours, and freeze-dry to obtain cysteine-modified hyaluronic acid.

[0071] Among them, the molecular weight of sodium hyaluronate is 0.1MDa, carboxyl group in sodium hyaluronate: N-succinimide: 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride: half The m...

Embodiment 3

[0075](1) Dissolve 400mg sodium hyaluronate in 100mL deionized water, first add 230mg N-succinimide (NHS), fully dissolve; then add 770mg 1-ethyl-(3-dimethylaminopropyl) Carbodiimide hydrochloride (EDC·HCl) powder, adjust the pH=4.75 of the reaction solution with 1M NaOH and 1M HCl solution, and react for 2 hours; then add 10mL of 45.44mg / mL cysteine ​​( CSH·HCl) hydrochloride, react for 24 hours; finally adjust the pH of the reaction solution to 8.5 with 1M NaOH solution, add 10 mL of 186.0 mg / ml dithiothreitol (DTT) solution, and react for 12 hours.

[0076] (2) After the reaction, adjust the pH of the reaction solution to 3.0-3.5 with 1M HCl solution, dialyze in deionized water with pH=3.0-3.5 for 72 hours, and freeze-dry to obtain cysteine-modified hyaluronic acid.

[0077] Among them, the molecular weight of sodium hyaluronate is 0.1MDa, carboxyl group in sodium hyaluronate: N-succinimide: 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride: half The mass ratio of...

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Abstract

The invention discloses a preparation method and an application of sulfhydryl/disulfide bond controllable self-crosslinked hyaluronic acid hydrogel and belongs to the field of biological materials. The hydrogel is prepared from a sulfhydryl-hyaluronic acid compound with free sulfhydryl as a raw material; by adjusting the sulfhydryl density (10-60%), the gel temperature (4-37 DEG C) and the molecular weight (0.1M, 0.3M and 1M) of hyaluronic acid, and using the oxidation-reduction transformation characteristics between sulfhydryl and disulfide bonds to control the forming time, degradation time and the mechanical properties of the gel, a controllable and injectable type intelligent hydrogel with a good three-dimensional network crosslinked structure is constructed. Meanwhile, the hydrogel of the type is single in component, avoids the introduction of exogenous toxic substances before and after gel forming, and has good biocompatibility and degradation performance. Based on the research discovery, the controllable self-crosslinked high-polymer polymer can be applied to minimally invasive repairing of tissue engineering in-situ damages and construction of an intelligent adjustable three-dimensional cell culture scaffold.

Description

technical field [0001] The invention belongs to the field of biological materials, and in particular relates to a hyaluronic acid hydrogel with controllable self-crosslinking of thiol / disulfide bonds, a preparation method and application thereof. technical background [0002] Tissue engineering, also known as "regenerative medicine", refers to the technology of using biologically active substances to rebuild or repair organs and tissues through in vitro culture or construction. This concept was proposed by the National Science Foundation of the United States in 1987, and it was officially defined in 1988 as: applying the principles and technologies of life science and engineering to correctly understand the tissue structure and function of mammals in both normal and pathological states On the basis of the relationship between human beings, it is an emerging discipline to research and develop biological substitutes for repairing, maintaining, and promoting the functions and s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08J3/24C08L5/08A61L27/20A61L27/58
Inventor 孙勇樊渝江边少荃曹万旭张兴栋
Owner SICHUAN UNIV
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