Injectable high-strength and temperature-sensitive modified chitin-based hydrogel as well as preparation method and application thereof

A temperature-sensitive, high-strength technology, applied in the field of biomedical materials and tissue engineering, can solve problems such as weak material strength, and achieve the effects of easy industrial production, good biocompatibility, and simple and fast preparation methods

Active Publication Date: 2018-07-24
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the temperature-sensitive chitin derivatives are weak in physical gelation at elevated temperatures

Method used

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  • Injectable high-strength and temperature-sensitive modified chitin-based hydrogel as well as preparation method and application thereof
  • Injectable high-strength and temperature-sensitive modified chitin-based hydrogel as well as preparation method and application thereof
  • Injectable high-strength and temperature-sensitive modified chitin-based hydrogel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: the synthesis of hydrophilic macromolecular cross-linking agent

[0038] 1. Synthesis of benzaldehyde-modified polyethylene glycol (PEG) macromolecular cross-linking agent

[0039] (1) Synthesis of linear bisbenzaldehyde-terminated PEG (DF-PEG)

[0040] Benzaldehyde with linear PEG end group Linear bisbenzaldehyde end group PEG

[0041] Weigh 1.5 gram of PEG 6k and 0.19 gram of 4-carboxybenzaldehyde and place in a 100mL round bottom flask, add 30mL of dried methylene chloride to dissolve, then add 0.15 gram of 4-dimethylaminopyridine (DMAP) and 0.31 gram of dicyclohexylcarbodiimide (DCC), stirred and reacted at room temperature for 24 hours, filtered and collected the filtrate and precipitated in a large amount of ether, and the collected crude product was dissolved, recrystallized and dried in isopropanol to obtain bifunctional benzaldehyde PEG, 79% yield. 1 H NMR (500MHz, CDCl 3 ,δ): 10.1 (hydrogen on the aldehyde functional group), 8.2, 7.9 (hydroge...

Embodiment 2

[0052] Embodiment 2: Preparation of thermosensitive chitin derivative A

[0053] Preparation of thermosensitive hydroxypropyl chitin (HPCH)

[0054] According to our previous research work [Chinese invention patent application publication specification CN201410170871.8], a homogeneous method was used to prepare hydroxypropyl chitin with a low degree of deacetylation in a sodium hydroxide-urea system. Weigh 2 grams of purified chitin (viscosity-average molecular weight is 756,000) and stir and disperse it in 100 grams of aqueous solution containing 11wt% sodium hydroxide and 4wt% urea in advance, freeze overnight at -25°C, take it out at room temperature Under mechanical stirring to thaw it, and then repeat the freezing and thawing twice to obtain the dissolved chitin aqueous solution. Add 11.5 grams of propylene oxide to the obtained chitin solution (100 grams, 2 wt%), and the system is mechanically stirred at 2°C for 2 hours to mix the reactants evenly, then the temperature ...

Embodiment 3

[0060] Example 3: Preparation of thermosensitive ammonia aldehyde in situ reaction modified hydroxypropyl chitin HPCH hydrogel

[0061] The DF-PEG prepared in Example 1 (the molecular weight of PEG is 2000) and the thermosensitive hydroxypropyl chitin HPCH-T1 prepared in Example 2 were respectively dissolved in 0.15M PBS buffer at pH 7.4, and the concentration of A solution of 20 wt% DF-PEG and 3 wt% HPCH-T1. Take 0.047g of DF-PEG solution, 1g of HPCH-T1 solution and 0.14g of PBS buffer solution and mix them uniformly at 2-15°C for half a minute at low temperature (it is liquid for a long time after mixing at low temperature, and has good injectability properties) It was placed in a constant temperature water bath at 37°C and quickly formed a gel, which illustrated its in-situ rapid gelation characteristics in vivo. Because the chemical crosslinking of ammonia aldehyde proceeds slowly in the body, in a constant temperature water bath at 37°C for 6-24 hours, a hydrogel with a ...

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Abstract

The invention discloses injectable high-strength and temperature-sensitive modified chitin-based hydrogel as well as a preparation method and application thereof. The gel is characterized in that a temperature-sensitive chitin derivative is dissolved into a water system at low temperature and a crosslinking agent or a photoinitiator is introduced to form an injectable hydrogel precursor solution with good flowability; after the injectable hydrogel precursor solution is injected into a body, the injectable high-strength hydrogel is formed through spontaneous chemical crosslinking or light illumination crosslinking under physiological conditions. The hydrogel disclosed by the invention has abundant precursor material sources and is easy to prepare; the photoinitiator or the crosslinking agent, which has relatively good solubility and very low toxicity in water, is used. The temperature-sensitive chitin derivative is utilized and can be physically cross-linked and molded under the physiological conditions and is further subjected to chemical crosslinking or photocrosslinking to prepare the injectable high-strength hydrogel and the injectable high-strength hydrogel does not need to besubjected to any post-treatment. Furthermore, the hydrogel has biodegradability and can be widely used for fields including biomedical materials, tissue engineering technologies and the like.

Description

technical field [0001] The invention belongs to the field of biomedical materials and tissue engineering, and specifically relates to an injectable intelligent high-strength chitin-based hydrogel product and its preparation method and application. Background technique [0002] Polymer hydrogel is a cross-linked polymer with a three-dimensional network structure that absorbs a large amount of water and is insoluble in water. Because it is close to the extracellular matrix, it has good hydrophilicity, excellent swelling performance and biocompatibility etc., have broad application prospects in the fields of biomedicine and tissue engineering materials. For example, as a medical device, hydrogel can be used for wound dressing, adhesion, sealing and anti-leakage during surgery, hemostasis during surgery, tissue filling, anti-adhesion after surgery, or can evenly wrap cells, proteins, peptides, hormones, etc. Various bioactive substances and drug carriers and tissue engineering ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/26A61L27/52A61L24/04A61L24/08A61L31/04A61L31/06A61L31/14C08B37/08
CPCA61L24/0031A61L24/043A61L27/26A61L27/52A61L31/041A61L31/145A61L2400/04A61L2400/06C08B37/003C08L5/08C08L71/02
Inventor 蒋序林毕波袁蒙黄佳昌
Owner WUHAN UNIV
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