阅读说明：本技术 一种稀土微纳米材料与甲壳素复合骨植入材料及制备方法 (Rare earth micro-nano material and chitin composite bone implant material and preparation method thereof ) 是由 黄晶 利月珍 李莉 杨潮晖 蔡忠星 王菲 于 2021-09-24 设计创作，主要内容包括：本发明公开了一种稀土微纳米材料与甲壳素复合骨植入材料及制备方法,通过机械搅拌、超声处理将碱性水溶液、稀土微纳米材料、甲壳素粉充分混合后得到均匀混合液；将混合液转移至聚四氟乙烯的模具中,放置在-20℃至-30℃的条件下冷冻,然后反复冻融,脱模后得到甲壳素凝胶；将甲壳素凝胶放入甘油或无水乙醇里浸泡,取出后用去离子水洗涤,直至洗涤至中性即得到复合骨植入材料。本发明以甲壳素为骨植入材料基体,引入稀土微纳米材料,通过低温冻融法,优化制备条件,制备出具有适宜孔径、高孔隙率和良好机械强度及多功能性的骨支架材料,干燥后可形成类似骨髓腔的中空仿生结构,对骨修复和再生的研究具有重要的意义。(The invention discloses a rare earth micro-nano material and chitin composite bone implant material and a preparation method thereof, wherein an alkaline aqueous solution, the rare earth micro-nano material and chitin powder are fully mixed through mechanical stirring and ultrasonic treatment to obtain a uniform mixed solution; transferring the mixed solution into a polytetrafluoroethylene mold, freezing at-20 to-30 ℃, repeatedly freezing and thawing, and demolding to obtain chitin gel; and (3) soaking the chitin gel in glycerol or absolute ethyl alcohol, taking out, washing with deionized water until the gel is neutral, and thus obtaining the composite bone implant material. The invention takes chitin as a bone implant material matrix, introduces rare earth micro-nano materials, prepares a bone scaffold material with proper pore diameter, high porosity, good mechanical strength and multiple functions by optimizing preparation conditions through a low-temperature freeze thawing method, can form a hollow bionic structure similar to a marrow cavity after drying, and has important significance for research on bone repair and regeneration.)

1. A preparation method of a rare earth micro-nano material and chitin composite bone implant material is characterized by comprising the following steps:

fully mixing an alkaline aqueous solution, a rare earth micro-nano material and chitin powder through mechanical stirring and ultrasonic treatment to obtain a uniform mixed solution;

step two, transferring the mixed solution into a polytetrafluoroethylene mold, freezing at the temperature of-20 ℃ to-30 ℃, repeatedly freezing and thawing, and demolding to obtain chitin gel;

and step three, soaking the chitin gel in water or glycerol or absolute ethyl alcohol, taking out, washing with deionized water until the chitin gel is washed to be neutral, and thus obtaining the composite bone implant material.

2. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the first step specifically comprises:

and (2) placing 90-100 parts by weight of alkaline aqueous solution and 0.00769-2 parts by weight of rare earth in a beaker, mechanically stirring, carrying out ultrasonic treatment until solid particles are completely dispersed, weighing 7-11 parts by weight of chitin powder, adding the chitin powder into the mixed solution, continuously mechanically stirring until the chitin powder is dispersed in the mixed solution, then carrying out ultrasonic treatment on the mixed solution, taking out, and continuously carrying out mechanical stirring to obtain uniform mixed solution.

3. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the alkaline aqueous solution is urea alkaline solution or thiourea alkaline solution, and the alkali is sodium hydroxide.

4. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the rare earth micro-nano material is gadolinium oxide Gd₂O₃Gadolinium oxysulfide Gd₂O₂S, gadolinium phosphate GdPO₄·nH₂O, gadolinium fluoride GdF₃Barium gadolinium pentafluoride BaGdF₅One kind of (1).

5. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the mesh number of the chitin powder is 100-200 meshes respectively.

6. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the ultrasonic power is 20W-100W during ultrasonic treatment, and the ultrasonic time is 20-60 min.

7. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: the number of days of repeated freeze thawing is 3-9 days.

8. The method for preparing the rare earth micro-nano material and chitin composite bone implant material according to claim 1, wherein the method comprises the following steps: soaking chitin gel in water or glycerol or anhydrous alcohol for 1-72 hr.

9. A rare earth micro-nano material and chitin composite bone implant material is characterized in that: the preparation method of the rare earth micro-nano material and chitin composite bone implant material according to any one of claims 1-8 is used.

Technical Field

The invention relates to the field of bone implant materials, in particular to a rare earth micro-nano material and chitin composite bone implant material and a preparation method thereof.

Background

The ideal scaffold material for bone tissue engineering should have good biocompatibility, good biodegradability, three-dimensional porous structure, plasticity, certain mechanical strength, osteoinductivity, osteoconductivity and easy disinfection. For single autogenous bone, allogeneic bone, metal material, high molecular material or inorganic non-metallic material, these materials have different advantages and disadvantages respectively, therefore, the composite material can give play to its advantage comprehensively, make up for its deficiency, it is an important direction of bone implantation material research.

Among organic materials, natural polymer materials have good biocompatibility, and particularly Chitin (Chitin) materials, which are rich renewable resources with the chemical name of beta- (1,4) -2-amino-deoxy-D-glucose. Chitin is widely distributed in shellfish shells, insect shells, mollusks and algae skeletons. As a natural cationic biopolymer, chitin and its derivatives have good physicochemical properties (e.g., mechanical stability, thermal stability and adsorption capacity) and biological properties (e.g., biocompatibility, biodegradability and nontoxicity), and play a crucial role in hierarchical control of biomineralization system processes. The nano composite scaffold material prepared by utilizing the chitin shows good cell adhesion and protein adsorption performance. Therefore, the applications in the fields of food industry, material science, and tissue engineering are also attracting more and more attention. Although the chitin has poor solubility in media such as water, dilute acid, common organic solvents and the like, so that the application of the chitin is limited, the existing low-temperature freeze-thaw method promotes the linkage of hydrogen bonds among chitin molecules, can form a solid material with uniform body system, provides a solid foundation for the application of the chitin in bone implant materials, and has great preparation process, mechanical property optimization and promotion space, thereby having important significance of further research.

Since 1794 discovered by Finnish chemist-Jiadolin (John Gadolin), rare earths have gradually explored their application in various fields due to their excellent optical, electrical, and magnetic effects. The introduction of rare earths has promoted the jump in human science and technology from military, metallurgy, petrochemical, to glass ceramics for photovoltaic materials, to agricultural fields. For example, after the rare earth is added into steel, cast iron and nonferrous metal, the physical and chemical properties of the metal material can be changed, so that the shaping, toughness, corrosion resistance, wear resistance and fatigue resistance of the metal material can be improved. With the development of the micro-nano material in the twentieth century, the research and development of the rare earth material are still not completed, and scientists hope that the rare earth micro-nano material brings further innovation and innovation of the technology from the regulation and synthesis of the rare earth micro-nano material to the development and application of the rare earth micro-nano material in a new field. Among biomedical materials, rare earth materials which are concerned in the early stage include cerium nitrate-silver sulfadiazine, lanthanum carbonate, gadolinium-based contrast agents and the like, which are respectively used for treating deep burn, hyperphosphatemia caused by end-stage renal failure and Magnetic Resonance Imaging (MRI) contrast, the action mechanism and the biological safety of the rare earth materials are also researched and discussed in succession, and most of people think that the biological effect of the rare earth materials presents two aspects of concentration dependence, namely low-concentration positive effect and high-concentration negative effect (hermesis effect). Current studies also confirm this hypothesis. In 2019, the x.h.cheng group modified Carbon Nanotubes (CNTs) with Rare Earth (RE) lanthanum chloride to obtain rare earth modified Carbon Nanotubes (CNTs), and incorporated into epoxy resins (EP) to prepare composite materials. Compared with pure EP, the untreated carbon nanotubes (CNTs/EP), the carbon nanotubes prepared by acidification (ACNTs/EP), the acidified carbon nanotubes and the rare earth synergistic modification (REACNTs/EP) respectively improve the ultimate tensile strength and the tensile modulus of the RECNTs/EP by 33.9 percent and 73.7 percent, and respectively improve the performances of the REACNTs/EP by 50.7 percent and 90.9 percent, which shows that RE has good effect on improving the mechanical properties of the carbon nanotube reinforced composite material. Therefore, it is the focus of the current research to fully develop and utilize the specificity of the rare earth micro-nano material and explore and expand a new and suitable application direction.

Since there are 7 unpaired in the rare earth gadolinium 4f orbitalElectronically, in the context of organic materials, water-soluble gadolinium-containing particles are useful as MRI contrast agents for tumor diagnosis, which have been used clinically for many years. In the field of inorganic materials, research is mainly focused on two directions: firstly, morphology regulation and control of rare earth micro-nano materials and research of fluorescence properties of the rare earth micro-nano materials; and secondly, the particle size/morphology of the rare earth micro-nano particles is regulated and controlled and the research of the rare earth micro-nano particles in the biomedical direction is carried out, such as the treatment of cancers through biological imaging, drug transportation, photo-thermal treatment and the like. In the bone implant material, apart from the research on the rare earth doped metal matrix bone implant material, the research on rare earth inorganic micro-nano particles in the bone implant material is less. The rare earth elements and calcium ions have similar ionic radii, and the rare earth ions have higher charges and are used for Ca on biological molecules²⁺The sites have a high affinity and are therefore also commonly referred to as Ca²⁺An inhibitor or a probe. By utilizing the characteristic, the rare earth inorganic micro-nano material has potential application in bone implant materials. Meanwhile, the magnetic resonance imaging tracer effect on natural polymer bone implant materials such as chitin base and the like can be achieved by combining the paramagnetism of gadolinium.

Based on the analysis, if the natural polymer chitin and the rare earth inorganic gadolinium-containing micro-nano material can be compounded and dried to form a hollow bionic structure similar to a marrow cavity, the multifunctional performances such as mechanical property, biocompatibility/bioactivity, traceability and the like of the composite material are comprehensively improved, a new possibility is provided for the development of an orthopedic implantation instrument.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides a rare earth micro-nano material and chitin composite bone implant material and a preparation method thereof.

In order to achieve the purpose, the invention is implemented according to the following technical scheme:

the invention provides a preparation method of a rare earth micro-nano material and chitin composite bone implant material, which comprises the following steps:

fully mixing an alkaline aqueous solution, a rare earth micro-nano material and chitin powder through mechanical stirring and ultrasonic treatment to obtain a uniform mixed solution;

step two, transferring the mixed solution into a polytetrafluoroethylene mold, freezing at the temperature of-20 ℃ to-30 ℃, repeatedly freezing and thawing, and demolding to obtain chitin gel;

and step three, soaking the chitin gel in water or glycerol or absolute ethyl alcohol, taking out, washing with deionized water until the chitin gel is washed to be neutral, and thus obtaining the composite bone implant material.

Further, the first step specifically includes:

and (2) placing 90-100 parts by weight of alkaline aqueous solution and 0.00769-2 parts by weight of rare earth in a beaker, mechanically stirring, carrying out ultrasonic treatment until solid particles are completely dispersed, weighing 7-11 parts by weight of chitin powder, adding the chitin powder into the mixed solution, continuously mechanically stirring until the chitin powder is dispersed in the mixed solution, then carrying out ultrasonic treatment on the mixed solution, taking out, and continuously carrying out mechanical stirring to obtain uniform mixed solution.

Further, the alkaline aqueous solution is urea alkaline solution or thiourea alkaline solution, and the alkali is sodium hydroxide.

Further, the rare earth micro-nano material is gadolinium oxide Gd₂O₃Gadolinium oxysulfide Gd₂O₂S, gadolinium phosphate GdPO₄·nH₂O, gadolinium fluoride GdF₃Barium gadolinium pentafluoride BaGdF₅One kind of (1).

Furthermore, the mesh number of the chitin powder is 100-200 meshes respectively.

Furthermore, the ultrasonic power is selected from 20W to 100W during ultrasonic treatment, and the ultrasonic time is 20 min to 60 min.

Further, the number of days of repeated freeze thawing is 3-9 days.

Further, the chitin gel is soaked in water or glycerol or absolute ethyl alcohol for 1-72 h.

The second purpose of the invention is to provide a rare earth micro-nano material and chitin composite bone implant material, which is prepared by using the preparation method of the rare earth micro-nano material and chitin composite bone implant material.

Compared with the prior art, the invention has the following beneficial effects:

(1) the natural polymer chitin is a material with good biocompatibility and bioactivity, and the chitin is used as a matrix of the bone implant material, so that renewable resources can be fully utilized, and the resources can be efficiently recycled.

(2) The bone scaffold material with proper pore size, high porosity, good mechanical strength and multiple functions is prepared by taking chitin as a bone implant material matrix, introducing a rare earth micro-nano material, optimizing preparation conditions through a low-temperature freeze thawing method, and forming a hollow bionic structure similar to a marrow cavity after drying, thereby having important significance for research on bone repair and bone regeneration.

(3) The preparation process is simple to operate, the synthesis process is stable, the requirement on equipment is not high, and industrialization is easy to realize.

Drawings

Fig. 1 is an SEM image of the pore structure of the pure chitin bone scaffold of the present invention after drying and freeze-drying.

Fig. 2 is a diagram of a pure chitin scaffold of comparative example 1 by different treatment methods.

FIG. 3 is a T-shape of the rare earth/chitin composite bone implant material prepared in example 1 after drying₁Weighted Magnetic Resonance Imaging (MRI) map.

FIG. 4 is a wet stress-strain curve of the RE/chitin composite bone implant material prepared in example 1.

Fig. 5 is a stress-strain curve diagram of the chitin bone scaffold obtained by drying the composite bone implant material of example 1 and comparative examples 1-7.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The specific embodiments described herein are merely illustrative of the invention and do not limit the invention.

The raw materials and reagents used in the following examples are all commercially available raw materials and reagents.

Example 1

75ml of water, 11g of sodium hydroxide and 4g of urea are weighedPlacing in a beaker, mechanically stirring until the solution becomes clear and transparent, and weighing 0.00769 gadolinium oxide Gd₂O₃Adding the chitin into the mixed solution, mechanically stirring, performing ultrasonic treatment (ultrasonic time is 30min, ultrasonic power is 80W) until solid particles are completely dispersed, weighing 10g of chitin with 200 meshes, adding the chitin into the mixed solution, continuously performing mechanical stirring until chitin powder is dispersed in the mixed solution, then performing ultrasonic treatment on the mixed solution, taking out the mixed solution, continuously performing mechanical stirring, transferring a reactant into a polytetrafluoroethylene mold, placing the mold for freezing and repeated freezing and thawing at-20 ℃ for 5 days, demolding to obtain chitin gel, placing the chitin gel into absolute ethyl alcohol for soaking for 15h, taking out, washing with deionized water until the chitin gel is neutral to obtain a composite bone implant material, and drying to obtain the rare earth chitin composite bone scaffold.

Example 2

75ml of water, 11g of sodium hydroxide and 4g of urea are weighed and placed in a beaker, mechanical stirring is carried out until the solution becomes clear and transparent, and 2g of gadolinium oxysulfide Gd₂O₂S, adding the chitin into the mixed solution, mechanically stirring, carrying out ultrasonic treatment (ultrasonic time is 30min, ultrasonic power is 80W) until solid particles are completely dispersed, weighing 200 meshes of chitin, adding the chitin into the mixed solution, continuously mechanically stirring until chitin powder is dispersed in the mixed solution, then carrying out ultrasonic treatment on the mixed solution, taking out the mixed solution, continuously carrying out mechanical stirring, transferring a reactant into a polytetrafluoroethylene mold, placing the mold for freezing and repeated freezing and thawing at-30 ℃ for 3 days, demolding to obtain chitin gel, placing the chitin gel into glycerol for soaking for 1h, taking out, washing with deionized water until the mixture is neutral, thus obtaining the composite bone implant material, and drying to obtain the rare earth chitin composite bone scaffold.

Example 3

75ml of water, 11g of sodium hydroxide and 4g of urea are weighed into a beaker, mechanical stirring is carried out until the solution becomes clear and transparent, and 0.0231g of gadolinium fluoride GdF is weighed₃Adding into the mixed solution, mechanically stirring, and performing ultrasonic treatment (ultrasonic time is 30min, and ultrasonic power is 20-80W) until solid particles are completely removedAfter dispersion, weighing 10g of chitin with 150 meshes, adding the chitin into the mixed solution, continuously mechanically stirring until chitin powder is dispersed in the mixed solution, then carrying out ultrasonic treatment on the mixed solution, taking out the mixed solution, continuously mechanically stirring, transferring the reactant into a polytetrafluoroethylene mold, placing the polytetrafluoroethylene mold for freezing and repeatedly freezing and thawing for 5 days at the temperature of-25 ℃, demolding to obtain chitin gel, soaking the chitin gel in water for 72 hours, taking out the chitin gel, washing the chitin gel with deionized water until the chitin gel is neutral to obtain a composite bone implant material, and drying to obtain the rare earth chitin composite bone scaffold.

For comparison with the chitin bone scaffold prepared by adding rare earth, some comparative examples were set based on the above example 1.

Comparative example 1

The difference from the example 1 is that the pure chitin bone scaffold is obtained after drying without adding rare earth, and the SEM picture is shown in figure 1.

Comparative example 2

The difference from the embodiment 1 is that no rare earth is added, the added material is sodium alginate, and the dosage is 0.1-0.9 g.

Comparative example 3

The difference from the embodiment 1 is that no rare earth is added, the additive material is gelatin, and the dosage is 0.5-2.5 g.

Comparative example 4

The difference from the embodiment 1 is that no rare earth is added, the additive material is sodium carboxymethyl cellulose, and the dosage is 0.2-1 g.

Comparative example 5

The difference from the embodiment 1 is that no rare earth is added, the additive material is microcrystalline cellulose, and the dosage is 1-3 g.

Comparative example 6

The difference from the example 1 is that rare earth is not added, and the stent is soaked by sodium citrate with the dosage of 1-9 g.

Comparative example 7

The difference from the example 1 is that rare earth is not added, and the stent is soaked by glycerol with the dosage of 25-40 g.

Fig. 2 is a diagram of a pure chitin scaffold of comparative example 1 by different treatment methods.

FIG. 3 is a T-shape of the rare earth/chitin composite bone implant material prepared in example 1 after drying₁Weighted Magnetic Resonance Imaging (MRI) map. It can be seen that the composite scaffold has good nuclear magnetic tracer property after being doped with rare earth.

FIG. 4 is a wet stress-strain curve of the RE/chitin composite bone implant material prepared in example 1. It can be seen that at appropriate concentrations, the incorporation of rare earths can promote the mechanical properties of the scaffold material.

Fig. 5 is a stress-strain curve diagram of the chitin bone scaffold obtained by drying the composite bone implant material of example 1 and comparative examples 1-7. As can be seen from FIG. 4, the composite bone implant material prepared by the invention has better compression strength with the maximum compression strength of 6.5 MPa.

The technical solution of the present invention is not limited to the limitations of the above specific embodiments, and all technical modifications made according to the technical solution of the present invention fall within the protection scope of the present invention.