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A highly biomimetic bone matrix hybrid cross-linked porous membrane for skull repair and its preparation method

A hybrid cross-linked, porous membrane technology, applied in tissue regeneration, prostheses, medical science, etc., can solve problems such as HAp aggregation, uneven dispersion, and limited compatibility of inorganic phases, so as to reduce uncontrollable clinical risks, Effect of promoting transport and cell migration, promoting adhesion

Active Publication Date: 2021-10-26
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing bioactive hydrogel / HAp composites have the problems of agglomeration and uneven dispersion of HAp in the composite, and limited compatibility between the inorganic phase and the organic phase.

Method used

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  • A highly biomimetic bone matrix hybrid cross-linked porous membrane for skull repair and its preparation method
  • A highly biomimetic bone matrix hybrid cross-linked porous membrane for skull repair and its preparation method
  • A highly biomimetic bone matrix hybrid cross-linked porous membrane for skull repair and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064]In this example, the preparation of dopamine-modified hyaluronic acid (HAD), the steps are as follows:

[0065] (1) Add a concentration of 84mg / mL N-hydroxysuccinimide (NHS) solution dropwise to a sodium hyaluronate (Mw=2000kDa) aqueous solution with a concentration of 21mg / mL, and then add dropwise a concentration of 200mg / mL 1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) solution, stirred for 4 hours, added dropwise an aqueous solution of dopamine hydrochloride with a concentration of 3 mmol / L, stirred for 24 hours, twice During the stirring reaction process, the pH value was controlled at 6.0, and the operation of this step was carried out under nitrogen protection. The molar ratio of EDCI, NHS, dopamine hydrochloride and carboxyl groups on sodium hyaluronate was 7:5:4:1;

[0066] (2) Dialyze the reaction solution obtained in step (1) with a dialysis membrane (MW=3.5-8kDa) in ultrapure water with a pH value of 4 for 72h, and vacuum freeze-dry to obt...

Embodiment 2

[0069] In this example, a highly biomimetic bone matrix hybrid cross-linked porous membrane for skull repair (HCLM) was prepared. The schematic diagram of the preparation process is shown in figure 1 ,Proceed as follows:

[0070] The HAD with a dopamine grafting rate of 10% prepared in Example 1 was dissolved in deionized water, vortexed until transparent and clear, to obtain a HAD solution with a concentration of 25 mg / mL, and collagen type I (ColI) was dissolved in 0.5 mol / L acid solution to obtain a concentration of 25mg / mL ColI solution.

[0071] Add the micron-sized spherical HAp slurry with a solid content of 35wt.% to the HAD solution under ice bath conditions, and use the probe of the cell disruptor to ultrasonically disperse for 15 minutes, then add the ColI solution dropwise, and use the probe of the cell disruptor to fully ultrasonically disperse, micron-sized The addition of spherical HAp slurry, HAD solution and ColI solution should make the mass ratio of micron-...

Embodiment 3

[0091] In this example, HCLM was prepared and tested for tensile stress and immediate fixation performance.

[0092] The HAD with a dopamine grafting rate of 10% prepared in Example 1 was dissolved in deionized water, vortexed until transparent and clear, to obtain a HAD solution with a concentration of 25 mg / mL, and collagen type I (ColI) was dissolved in 0.5 mol / L acid solution to obtain a concentration of 25mg / mL ColI solution.

[0093] Add the micron-sized spherical HAp slurry with a solid content of 35wt.% to the HAD solution under ice bath conditions, and use the probe of the cell disruptor to disperse ultrasonically for 15 minutes, then add the type I collagen solution dropwise, and use the probe of the cell disrupter to fully ultrasonically disperse, The addition amount of micron spherical HAp slurry, HAD solution and ColI solution should make the mass ratio of micron spherical HAp, HAD and ColI be 2:5:5; then use 1mol / L NaOH solution under ultrasonic condition to mix ...

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Abstract

The invention provides a highly bionic bone matrix hybrid cross-linked porous membrane for skull repair, which is composed of a double-cross-linked polymer three-dimensional network and micron-sized spherical hydroxyapatite evenly distributed in the double-cross-linked polymer three-dimensional network , a porous membrane with an interpenetrating network structure; the double cross-linked polymer three-dimensional network is a polymer material with carboxyl and catechol functional groups oxidative self-crosslinking, a polymer material with carboxyl and catechol functional groups and a polymer material with amino and carboxyl groups The polymer material is formed by Michael addition reaction, and the phenolic hydroxyl group on the polymer material with carboxyl and catechol functional groups is chelated with calcium ions dissociated from micron-sized spherical hydroxyapatite. The invention can improve the dispersibility of the hydroxyapatite in the material, increase the integration degree of the hydroxyapatite and the organic phase, and realize the remodeling and regeneration of the skull defect without exogenous cells or growth factors.

Description

technical field [0001] The invention belongs to the field of bone repair materials, and relates to a highly bionic bone matrix hybrid cross-linked skull repair porous membrane and a preparation method thereof. Background technique [0002] Skull defects caused by trauma, tumor resection or infection pose a great clinical challenge worldwide. The incidence of craniocerebral trauma is increasing year by year. According to incomplete statistics, the number of skull defects caused by craniocerebral trauma in my country is as high as 1-200 / 100,000 people every year, and its mortality and disability rate ranks first among all types of trauma , Traumatic brain injury has also become an important threat to human health. Considering the clinical treatment effect and economic benefits of patients, choosing suitable cranioplasty materials is the most severe challenge in cranial defect repair. [0003] Currently, autologous and allogeneic bone grafts account for more than 90% of grafts...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/56A61L27/12A61L27/50A61L27/58A61L27/24A61L27/20A61L27/54
CPCA61L27/12A61L27/20A61L27/24A61L27/50A61L27/54A61L27/56A61L27/58A61L2300/112A61L2300/412A61L2430/02C08L5/08
Inventor 孙勇樊渝江卢恭恭徐杨
Owner SICHUAN UNIV
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