Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof

A composite structure, biomimetic mineralization technology, applied in tissue regeneration, medical science, prosthesis, etc., can solve the problem of inability to form highly compatible organic-inorganic complexes, achieve good biocompatibility, wide source of raw materials, The effect of reducing clinical risk

Active Publication Date: 2020-12-15
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, SBF biomimetic mineralization usually results in heterogeneous nucleation of bone-like apatite on the surface

Method used

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  • Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof
  • Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof
  • Biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] In this example, the preparation of dopamine-modified hyaluronic acid (HAD), the steps are as follows:

[0061] (1) To the sodium hyaluronate (Mw=340kDa) aqueous solution with a concentration of 11.5mg / mL, add a solution of N-hydroxysuccinimide (NHS) with a concentration of 46mg / mL dropwise, and then add a solution with a concentration of 150mg / mL 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) solution, stirred for 2 hours, added dropwise an aqueous solution of dopamine hydrochloride with a concentration of 2 mmol / L, stirred for 12 hours, two The pH value was controlled at 5.0 during the stirring reaction process, and the operation of this step was carried out under nitrogen protection. The molar ratio of EDCI, NHS, dopamine hydrochloride and the carboxyl group on sodium hyaluronate was 6:4:3:1;

[0062] (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 3.5 for 48 hours,...

Embodiment 2

[0065] In the present embodiment, the hydrogel (DCLH hydrogel), Col I hydrogel and HAD hydrogel with double cross-linked polymer network structure are prepared, and the steps are as follows:

[0066] (1) Dissolve the HAD powder prepared in Example 1 in deionized water, vortex until transparent and clear, and obtain a HAD solution with a concentration of 25 mg / mL, and dissolve type I collagen (Col I) in 0.5 mol / L A Col I solution with a concentration of 25 mg / mL was obtained in the acid solution. The Col I solution was slowly added dropwise to the above mixed solution, vortexed under ice bath conditions to mix the two fully, then the pH value of the resulting mixed solution was adjusted to 7.5 with 1mol / L NaOH solution, and quickly transferred to silica gel Stand still in the mold (diameter 8mm, height 2mm) for 24h, so that each component is fully cross-linked, and DCLH hydrogel is obtained.

[0067] In this example, three groups of DCLH hydrogels were prepared by controlling ...

Embodiment 3

[0075] In this example, the biomimetic mineralized hydrogel was prepared, and the steps were as follows:

[0076] (1) Prepare simulated body fluid, the simulated body fluid is 1.5×SBF.

[0077] Soak glass beakers, plastic beakers, and other containers used in the experiment in an acid bath. Measure 700mL of deionized water, add 0.1mmolNaCl, 0.02mmolNaHCO in sequence 3 , 0.05mmolKCl, 0.01mmolK 2 HPO 4 ·3H 2 O, 0.025 mmol MgCl 2 ·6H 2 O, 0.01 mmol CaCl2 and 1 mmol Na 2 SO 4 Dissolve it in deionized water and adjust the pH to 7.40 with tris(hydroxymethyl)aminomethane and 1mol / L HCl aqueous solution at 36.5°C, and adjust the volume to 1L to prepare a simulated body fluid. Filter the prepared simulated body fluid with a 0.22 μm head filter.

[0078] (2) The three groups of DCLH hydrogels prepared in Example 2 were fully rinsed with deionized water, and dried with nitrogen flow to remove the moisture on the surface of the hydrogels, and then immersed in the simulated body f...

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Abstract

The invention provides biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density. The biomimetic mineralized hydrogel with nano-micron composite structure and highmineral density is composed of hydrogel with double-crosslinked polymer network structure, and bone-like apatite uniformly distributed on the double-crosslinked polymer network structure of the hydrogel; the hydrogel with the double-crosslinked polymer network structure is formed by oxidative self-crosslinking of a polymer material with carboxyl and catechol functional groups as well as Michael addition reaction between the polymer material with the carboxyl and the catechol functional groups and a polymer material with amino and carboxyl; and the bone-like apatite is formed by allowing complexation of the catechol functional groups in the double-crosslinked polymer network structure of the hydrogel and calcium ions as nucleation sites for bone-like apatite growth. More specifically, the bone-like apatite is micron-scale bone-like apatite aggregate formed by aggregation of nano-scale bone-like apatite. The invention further provides application of the biomimetic mineralized hydrogel inthe field of skull repair.

Description

technical field [0001] The invention belongs to the field of bone repair materials, and relates to a biomimetic mineralized hydrogel with nano-micron composite structure and high mineral density, a preparation method and application thereof. Background technique [0002] Using biomimetic mineralization, biological organisms can produce hierarchically structured minerals with unique functions in liquid, ambient temperature. Inspired by the layered structure of bone components in organic–inorganic composites, a biomimetic mineralization strategy was reported to prepare type I collagen (Col I) mineralized scaffolds for bone tissue engineering. As a structural template, Col I can facilitate the permeation of amorphous calcium phosphate (ACP) precursor ions into the interstitial space and crystallization into aligned hydroxyapatite nanocrystals. While collagen / apatite biomimetic mineralized scaffolds showed enhanced cell viability and improved osteogenic activity. However, biom...

Claims

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Application Information

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IPC IPC(8): A61L27/52A61L27/54A61L27/46C08B37/08
CPCA61L27/52A61L27/46A61L27/54C08B37/0072A61L2430/02A61L2300/112C08L89/00C08L5/08
Inventor 孙勇樊渝江卢恭恭徐杨
Owner SICHUAN UNIV
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