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A mechanically enhanced gelatin frozen hydrogel and its preparation method and application

A technology of frozen water and hydrogel, applied in medical science, prosthesis, aerosol delivery, etc., can solve the problems of short degradation cycle, limited promotion, monomer residue, etc., achieve good biocompatibility, and prolong the degradation cycle Effect

Active Publication Date: 2022-03-29
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that factors such as poor mechanical properties and too short degradation cycle greatly limit the further promotion of these natural polymer gels in the field of tissue engineering.
Using small molecular monomers (such as acrylamide, etc.) to participate in cross-linking or doping with nanoparticles (such as hydroxyapatite (HA) and bioglass (BG), etc.) is a common way to improve the mechanical strength of cryogels. However, there will be problems such as monomer residues and limited increase: For example, Song et al. used BG to be incorporated into GelMA jelly to increase the calculated value of Young's modulus from about 80kpa to about 170kpa (Song K, Seunghun L, Sivashanmugam A, et al. al.Bioglass-Incorporated Methacrylated Gelatin Cryogel for Regeneration of Bone Defects[J].Polymers,2018,10(8):914.); Gu et al. used HA nanowires to enhance GelMA gelatin, and its Young's modulus ranged from about Increase from 35Kpa to 55Kpa (20% strain) (Gu L, Zhang J, Li L, et al. Hydroxyapatitenanowire composited gelatin cryogel with improved mechanical properties and cell migration for bone regeneration[J].Biomedical Materials,2019.)
In addition, due to the osteogenic effect or vascularity of HA and BG particles, this kind of composite jelly is only suitable for bone repair or dressing, which is not conducive to broadening the practical application range of jelly

Method used

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  • A mechanically enhanced gelatin frozen hydrogel and its preparation method and application
  • A mechanically enhanced gelatin frozen hydrogel and its preparation method and application
  • A mechanically enhanced gelatin frozen hydrogel and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Preparation of low solid content jelly (and load-bearing test)

[0041] (1) Preparation of GelMA and SF-GMA

[0042] Dissolve 1 g of gelatin in 10 ml of 1×PBS buffer at 50 °C, stir for 30 minutes until the gelatin is completely dissolved, and continuously inject 0.6 ml of methacrylic anhydride within 30 minutes using a micro-syringe pump, and then continue to react for 3 hours. The product was transferred to a 8-12kDA dialysis bag, and the dialysis was carried out at 40°C. The water was changed twice a day for 7 days. Store at low temperature.

[0043] Add 1 g of silk fibroin to 7 ml of saturated lithium bromide solution at 60°C and stir for 40 minutes to dissolve to obtain a silk fibroin solution. Add 0.3 ml of glycidyl methacrylate into the silk fibroin solution, and stir for 3 hours. , the stirring rate is 100-250rpm, the product is transferred to a 8-12kDA dialysis bag and dialyzed at 4°C, the water is changed twice a day for 3 days, the dialysis produc...

Embodiment 2

[0050] Example 2: Preparation of higher solid content jelly

[0051] (1) Preparation of GelMA, SF-GMA and APS solutions

[0052] GelMA, SF-GMA solution, etc. were prepared according to the method of Example 1, 0.45g APS was weighed and added to 15ml ultrapure water, stirred until APS was completely dissolved, and the APS solution was placed in a 4°C refrigerator for use.

[0053] (2) Preparation of GelMA / SF-GMA composite frozen hydrogel with higher solid content (15%)

[0054] Dissolve 1.2g of GelMA in 2.182ml of deionized water, then add 6.818ml of concentrated SF-GMA solution with a mass fraction of 8.8%, stand at 40°C for 5min, stir well, then add 60μl of TEMED and mix well, and finally add 3ml of APS solution and stirred for 10s to mix the material, then transfer it to the mold and store it at -30°C for cross-linking treatment (induced free radical cross-linking). The cross-linking treatment time is 24h. Frozen hydrogel molding.

[0055] (3) Post-processing of jelly

...

Embodiment 3

[0057] Example 3: Preparation of jelly with different solid content (also SEM morphology characterization)

[0058] (1) Preparation of GelMA, SF-GMA and APS solutions:

[0059] GelMA and SF-GMA solutions, etc. were prepared according to the method of Example 1, 0.45 g of APS was weighed and added to 15 ml of ultrapure water, dissolved and then placed in a 4°C refrigerator for use.

[0060] (2) Preparation of GelMA / SF-GMA composite jelly with different solid contents:

[0061] Add the components of the hydrogel precursor solution to a series of vials according to the parameters in Table 1 and mix them thoroughly. After adding the ammonium persulfate solution, immediately stir for 10 seconds to mix the precursor solution, and then transfer it to the mold immediately. and stored at -20 °C for 12 h to induce the formation of frozen hydrogels.

[0062] Table 1: Composition ratios of frozen hydrogels with different solid contents

[0063]

[0064](3) Post-processing and charac...

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Abstract

The invention discloses a mechanically reinforced gelatin frozen hydrogel, a preparation method and application thereof. The method comprises: compounding methacrylylated gelatin and glycidyl acrylate modified silk fibroin solution, adding ammonium persulfate / tetramethylethylenediamine initiator solution to realize free radical crosslinking at low temperature, using methanol solution Post-treatment induces SF-GMA molecular chains to form hydrophobic crystals (β-sheet structure), and the frozen hydrogel is obtained. The cryohydrogel has a nearly 200 μm through macroporous structure under swelling equilibrium conditions, its compressive modulus can be enhanced from 0.057Mpa to 0.523Mpa, and the degradation cycle in the environment containing type II collagenase is extended from 7 days to 28 The remaining 60% is degraded in one day, and has good biocompatibility. The method provided by the invention has a simple preparation process, effectively enhances the performance of the jelly, and has good application prospects in the fields of drug delivery, tissue repair and the like.

Description

technical field [0001] The invention relates to the technical field of the manufacture of composite hydrogel materials, in particular to a mechanically enhanced gelatin frozen hydrogel and a preparation method and application thereof. Background technique [0002] Macroporous hydrogels have the characteristics of high specific surface area and internal through-hole structure, and have the ability of rapid exchange of support substances and cell migration, so they have broad prospects in biomedical fields such as drug release, cell carriers and tissue engineering scaffolds. Because the macroporous gel prepared by the current porogen method often suffers from the defects of residual porogen and prone to closed-cell phenomenon, the frozen hydrogel (hereinafter referred to as jelly) prepared by the cryogelation method has become more and more popular in recent years. focus on. [0003] If the hydrogel is prepared by cross-linking below the freezing point of the system, it is ca...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/075C08H1/00A61K9/06A61K47/42A61L15/32A61L15/42A61L15/64A61L27/22A61L27/52A61L27/58C08L89/00
CPCC08J3/075A61K47/42A61K9/06A61L15/32A61L15/325A61L15/42A61L15/64A61L27/222A61L27/227A61L27/52A61L27/58A61L2430/02A61L2430/06C08J2389/00C08J2489/00C08L89/00
Inventor 方立明潘西满陈文祥钟华苏健裕
Owner SOUTH CHINA UNIV OF TECH
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