Double cross-linked integrated seamless composite hydrogel scaffold for articular cartilage repair

A composite hydrogel and hydrogel technology, applied in prosthetics, coatings, medical science, etc., can solve problems such as delamination of the osteocartilage interface, cell death, and the inability to realize the preparation of loaded cells, so as to improve the interface binding force , to avoid the effect of excessive calcification

Active Publication Date: 2020-10-16
AFFILIATED ZHONGSHAN HOSPITAL OF DALIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned electrostatic complexation technology, ion cross-linking technology, and 3D printing technology still have poor interface bonding force, and the osteochondral interface delamination phenomenon is prone to occur under the action of joint movement shea

Method used

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  • Double cross-linked integrated seamless composite hydrogel scaffold for articular cartilage repair
  • Double cross-linked integrated seamless composite hydrogel scaffold for articular cartilage repair
  • Double cross-linked integrated seamless composite hydrogel scaffold for articular cartilage repair

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] The preparation of double-crosslinked integrated seamless composite hydrogel scaffold includes the following steps:

[0045] (1) The sodium alginate molecule is reacted with 3-(p-benzylamino)-1,2,4,5-tetrazine (BAT) containing an azide group, so that the hydroxyl group of sodium alginate is grafted with azide Group (-N=N-), the grafting rate is 120% as characterized by nuclear magnetic mass spectrometry.

[0046] (2) Preparation of the subchondral bone layer: the final concentration of sodium alginate prepared in step (1) is 40g / L, and the bioceramic particles are evenly dispersed in the solution, and the content of the bioceramic particles in the solution is 1-100mg / L mL, aseptically defoamed, and stored at low temperature for future use.

[0047] Spread the mixed liquid into a thin film with a thickness of 3 mm, and prepare an ion-crosslinked hydrogel film through a calcium ion solution, that is, a subchondral bone layer hydrogel scaffold is prepared.

[0048] (3) P...

Embodiment 2

[0060] The preparation of double-crosslinked integrated seamless composite hydrogel scaffold includes the following steps:

[0061] (1) Grafting 3-(p-benzylamino)-1,2,4,5-tetrazine (BAT) containing azide group on the hydroxyl group of sodium alginate molecule, grafting the hydroxyl group of sodium alginate Azide group (-N=N-), NMR mass spectrometry shows that the grafting rate is 120%.

[0062] (2) Preparation of subchondral bone layer: preparation of mixed liquor, wherein the final concentration of sodium alginate containing step (1) prepared is 40g / L; the final concentration of collagen is 8g / L; and the bioceramic particles are uniformly dispersed in The above mixed solution is aseptically defoamed and stored at low temperature for future use.

[0063] Add mesenchymal stem cells to the above mixed solution at a cell density of 1×10 7 / mL;

[0064] The above mixed solution was spread into a thin film with a thickness of 3 mm, and an ion-crosslinked hydrogel film was prepar...

Embodiment 3

[0073] The preparation of double-crosslinked integrated seamless composite hydrogel scaffold includes the following steps:

[0074] (1) The carboxyl group of sodium alginate molecule is grafted with furfuryl amine containing furyl radicals, and the carboxyl group in sodium alginate and the amino-NH in furfuryl amine are used to 2 Amidation reaction occurs, and sodium alginate molecules are grafted with furan groups (C 4 h 4 (0), the grafting rate of furan radicals characterized by nuclear magnetic mass spectrometry is 75%.

[0075] (2) Preparation of subchondral bone layer: preparation of mixed liquor, wherein the final concentration of sodium alginate containing step (1) prepared is 40g / L; the final concentration of collagen is 8g / L; and the bioceramic particles are uniformly dispersed in The above mixed solution is aseptically defoamed and stored at low temperature for future use.

[0076] Add mesenchymal stem cells to the above mixture, and the cell density is 10 6 cell...

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Abstract

The invention relates to the technical field of tissue engineering articular cartilage repair, and specifically relates to a double cross-linked integrated seamless composite hydrogel scaffold for articular cartilage repair. The hydrogel scaffold successively includes a subchondral bone layer, a calcified interface layer and a cartilaginous layer from bottom to top; the subchondral bone layer is the hydrogel including bioceramic particles and alginate; the calcified interface layer is the polyelectrolyte electrostatic complex hydrogel including the alginate and polycation; the cartilaginous layer is the hydrogel including the alginate; and the alginate hydrogel in the subchondral bone layer, the calcified interface layer and the cartilaginous layer firstly forms ionic crosslinked hydrogeland then forms a double cross-linked integrated seamless structure through covalent crosslinking. The mechanical strength of the hydrogel scaffold is significantly superior to ionic crosslinked hydrogel scaffolds, so that interface bonding strength can be increased; and through the polyelectrolyte composite hydrogel membrane layer in the middle of the hydrogel scaffold, isolation effects on cartilage and subchondral bone microenvironment can be realized.

Description

technical field [0001] The invention relates to the technical field of tissue engineering articular cartilage repair, in particular to a subchondral bone-cartilage integrated double-crosslinked composite hydrogel scaffold used for articular cartilage repair throughout the whole process and a preparation method thereof. Background technique [0002] Articular cartilage injury is a common clinical disease. Articular cartilage lacks blood vessels, nerves, and lymphatic tissues, and contains very few cells, so its self-repair ability is limited. Therefore, it is difficult to restore articular cartilage damage to a healthy state no matter whether it is caused by physical or chemical factors. At present, the commonly used clinical methods for the treatment of cartilage injuries, such as minimally invasive drilling, microfracture, mosaic transplantation, periosteum or perichondrium transplantation, etc., although they can alleviate the pain of patients to a certain extent, the long...

Claims

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Application Information

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IPC IPC(8): A61L27/52A61L27/54A61L27/40A61L27/38C08J7/04C08J5/18C08L5/04
CPCA61L27/10A61L27/18A61L27/20A61L27/3808A61L27/3821A61L27/3834A61L27/3847A61L27/3852A61L27/52A61L27/54A61L2300/252A61L2300/412A61L2300/414A61L2430/02A61L2430/06C08J5/18C08J7/042C08J2305/04C08J2405/08C08L5/04C08L71/02
Inventor 赵德伟于炜婷郑国爽曹放张秀智
Owner AFFILIATED ZHONGSHAN HOSPITAL OF DALIAN UNIV
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