Supercharge Your Innovation With Domain-Expert AI Agents!

Rapidly curable hydrogel based on collagen and hyaluronic acid, its preparation method and application

A technology of hyaluronic acid and hydrogel, applied in prosthesis, medical science and other directions, can solve the problems of difficult chemical modification, low biocompatibility, incomplete degradation, etc., and achieve low toxicity, simple preparation method, excellent biological Compatibility effect

Active Publication Date: 2021-12-21
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most synthetic polymer materials have low biocompatibility and incomplete degradation. Therefore, natural polymer materials with good biocompatibility can be considered, but natural polymer materials are difficult to chemically modify, which limits their Applications

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Rapidly curable hydrogel based on collagen and hyaluronic acid, its preparation method and application
  • Rapidly curable hydrogel based on collagen and hyaluronic acid, its preparation method and application
  • Rapidly curable hydrogel based on collagen and hyaluronic acid, its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0071] In some embodiments, the preparation method includes: mixing hyaluronic acid, 3-(4-benzylamino)-1,2,4,5-tetrazine, a condensing agent and a first solvent to form a first mixed system A step of obtaining tetrazine-modified hyaluronic acid by amidation reaction; wherein, the reaction temperature is controlled at 15-30° C., and the reaction time is controlled at 10-20 hours.

[0072] Preferably, the condensing agent includes benzotriazol-1-yloxy tris(dimethylamino)phosphonium hexafluorophosphate and N,N-diisopropylethylamine; preferably, the transparent The molar ratio of uric acid to 3-(4-benzylamino)-1,2,4,5-tetrazine is 6-10:1; preferably, the molar ratio of the condensing agent to hyaluronic acid is 0.1- 0.5:1; Preferably, the first solvent includes dimethyl sulfoxide.

[0073] Further, the preparation method further includes: after the amidation reaction, post-treating the reaction product, the molecular weight cut-off of the dialysis bag used for dialysis in the pos...

Embodiment 1

[0090] Step 1: acidify an aqueous solution of sodium hyaluronate (Mw=36KDa) with a strongly acidic ion exchange resin Dowex 50W×8-100. Subsequently, the pH of the filtrate was adjusted to neutral by tetrabutylammonium hydroxide (TBA-OH), and then freeze-dried to obtain the product HA-TBA. HA-TBA and 1,2,4,5-tetrazineamine were dissolved in anhydrous DMSO, then pyBOP and DIEA were added and reacted overnight.

[0091] Among them, the reaction molar ratio of carboxyl group on HA-TBA, 1,2,4,5-tetrazine, pyBOP and DIEA is 8:1:1:1.

[0092] After the reaction in Step 1, the reaction solution was placed in a dialysis bag with a molecular weight cutoff of 3500 Da, dialyzed in deionized water for 1 day, and then purified by G-15 Sephadex chromatography column. Finally, freeze-dry to obtain tetrazine-modified hyaluronic acid (HA-Tz). The structural formula of hyaluronic acid modified by tetrazine is shown in formula (1):

[0093]

[0094] Wherein, the value of n is 115.

[0095]...

Embodiment 2

[0109] Step 1: acidify an aqueous solution of sodium hyaluronate (Mw=36KDa) with a strongly acidic ion exchange resin Dowex 50W×8-100. Subsequently, the pH of the filtrate was adjusted to neutral by tetrabutylammonium hydroxide (TBA-OH), and then freeze-dried to obtain the product HA-TBA. HA-TBA and 1,2,4,5-tetrazineamine were dissolved in anhydrous DMSO, then pyBOP and DIEA were added and reacted overnight.

[0110] Among them, the reaction molar ratio of carboxyl group on HA-TBA, 1,2,4,5-tetrazine, pyBOP and DIEA is 6:1:1:1.

[0111] After the reaction in Step 1, the reaction solution was placed in a dialysis bag with a molecular weight cut-off of 3500 Da, dialyzed in deionized water for 2 days, and then purified by G-15 Sephadex chromatographic column. Finally, freeze-dry to obtain tetrazine-modified hyaluronic acid (HA-Tz). The structural formula of hyaluronic acid modified by tetrazine is shown in formula (1):

[0112]

[0113] Wherein, the value of n is 115.

[01...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pore sizeaaaaaaaaaa
Login to View More

Abstract

The invention provides a rapidly curable hydrogel based on collagen and hyaluronic acid, its preparation method and application. The preparation method comprises: reacting 3-(4-benzylamino)-1,2,4,5-tetrazine with hyaluronic acid to obtain tetrazine-modified hyaluronic acid; generating amides of collagen and succinic anhydride reaction to obtain succinic anhydride-modified collagen, and then react 5-norbornene-2-methylamine with succinic anhydride-modified collagen to obtain norbornene-modified collagen; then tetrazine-modified hyaluronic acid and The norbornene-modified collagen was mixed evenly to undergo bioorthogonal reaction, and a rapidly curable hydrogel was obtained. The rapidly curable hydrogel obtained by the invention has short curing time, good biocompatibility and low toxicity, can provide cells with a three-dimensional living environment, and improve the adhesion and proliferation of stem cells on the three-dimensional support.

Description

technical field [0001] The invention belongs to the technical field of preparation of tissue engineering materials, and in particular relates to a rapidly curable hydrogel formed based on the bioorthogonal reaction between norbornene and tetrazine for three-dimensional culture of stem cells, as well as its preparation method and application. Background technique [0002] Tissue engineering is an effective way to treat organ failure or injury. Tissue engineering is an emerging multidisciplinary research field, which is the application of engineering and life science methods to prepare artificial tissues or organs, aiming at repairing damaged or worn tissues and organs in the body and restoring their functions. The three elements of tissue engineering are: biological scaffolds that support cell growth, cells, and growth factors that inducibly regulate cell activities. Among them, bioscaffold is a hot spot and difficulty in tissue engineering research. [0003] To be applied ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C08G81/00C08J3/075C08B37/08C08H1/00A61L27/24A61L27/20A61L27/56A61L27/52A61L27/50C08L87/00
CPCC08G81/00C08J3/075C08B37/0072C08H1/00A61L27/24A61L27/20A61L27/56A61L27/52A61L27/50C08J2387/00C08L5/08
Inventor 裴仁军昝悦刘敏
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com