阅读说明：本技术 基于改性钙钛矿量子点/氨基碳量子点的骨缺损修复材料及其制备方法 (Bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots and preparation method thereof ) 是由 王文爽 沈文齐 于 2020-12-23 设计创作，主要内容包括：本发明公开一种基于改性钙钛矿量子点的骨缺损修复材料及其制备方法,包括以下质量百分比原料：羟基磷灰石20～30％、磷酸八钙10～20％、骨形态发生蛋白0.5～2％、胶原蛋白1～5％、硫酸软骨素0.5～2％、羧甲基壳聚糖3～5％、改性钙钛矿量子点溶液补足余量；改性钙钛矿量子点/氨基碳量子点溶液的反应原料及质量份如下：钙钛矿量子点0.5～1.5份、二棕榈酰基磷脂酰乙醇胺8～16份、酸性氨基酸3～7份、还原型谷胱甘肽1～3份、EDC·HCl 0.5～1份、氯仿20～30份、去离子水100份。本发明首次在骨缺损修复材料中引入钙钛矿量子点、氨基碳量子点,利用量子点介导干细胞的转染,利用荧光显微成像技术监测干细胞行为变化；同时,诱导干细胞向成骨细胞和成软骨细胞方向分化,刺激骨细胞增殖再生。(The invention discloses a bone defect repairing material based on modified perovskite quantum dots and a preparation method thereof, wherein the bone defect repairing material comprises the following raw materials in percentage by mass: 20-30% of hydroxyapatite, 10-20% of octacalcium phosphate, 0.5-2% of bone morphogenetic protein, 1-5% of collagen, 0.5-2% of chondroitin sulfate, 3-5% of carboxymethyl chitosan and the balance of modified perovskite quantum dot solution; the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following reaction raw materials in parts by mass: 0.5-1.5 parts of perovskite quantum dots, 8-16 parts of dipalmitoyl phosphatidylethanolamine, 3-7 parts of acidic amino acid, 1-3 parts of reduced glutathione, 0.5-1 part of EDC & HCl, 20-30 parts of chloroform and 100 parts of deionized water. According to the invention, perovskite quantum dots and amino carbon quantum dots are introduced into a bone defect repair material for the first time, quantum dots are utilized to mediate the transfection of stem cells, and a fluorescence microscopic imaging technology is utilized to monitor the behavior change of the stem cells; meanwhile, stem cells are induced to differentiate towards osteoblasts and chondroblasts, and the proliferation and regeneration of the osteocytes are stimulated.)

1. A bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots is characterized by comprising the following raw materials in parts by mass:

the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following raw materials in parts by mass: 0.5-1 part of perovskite quantum dots, 0.6-1.2 parts of amino carbon quantum dots, 8-16 parts of phosphatidylserine, 3-5 parts of citric acid, 1-3 parts of reduced glutathione, 0.5-1 part of EDC & HCl, 20-30 parts of chloroform and 100 parts of deionized water; the preparation method of the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following steps:

i: adding phosphatidylserine into a chloroform solvent, magnetically stirring until the phosphatidylserine is completely dissolved, then adding the perovskite quantum dots, uniformly stirring, and carrying out rotary evaporation at the temperature of 60-70 ℃ to remove chloroform, thus obtaining the perovskite quantum dot lipid film;

ii: adding citric acid and reduced glutathione into deionized water, stirring and dissolving, then adding amino carbon quantum dots, and stirring and reacting at 40-50 ℃ for 1-2 hours to obtain an amino carbon quantum dot reaction solution;

iii: and adding the perovskite quantum dot lipid film into the obtained amino carbon quantum dot reaction liquid, stirring and dispersing, then heating to 50-60 ℃, adding EDC & HCl, and continuously stirring and reacting for 2-4 hours to obtain the modified perovskite quantum dot/amino carbon quantum dot solution.

2. The bone defect repair material based on the modified perovskite quantum dot/amino carbon quantum dot as claimed in claim 1, wherein the perovskite quantum dot comprises CsPbCl₃、CsPbBr₃、CsPbI₃、CsPbBr_3-xCl_x、CsPbBr_3-xI_x、CsSnCl₃、CsSnBr₃、CsSnI₃、CsSnBr_3-xCl_x、CsSnBr_3-xI_xOne or more of (a).

3. The bone defect repair material based on the modified perovskite quantum dots/amino carbon quantum dots as claimed in claim 2, characterized in that: x is more than 0 and less than 3.

4. The bone defect repair material based on the modified perovskite quantum dots/amino carbon quantum dots as claimed in claim 1, wherein the mass concentration of the calcium chloride solution is 0.5-1%.

5. The preparation method of the bone defect repairing material based on the modified perovskite quantum dots/amino carbon quantum dots as claimed in any one of claims 1 to 4, characterized by comprising the following steps:

s101: adding bone growth factors, collagen and chondroitin sulfate into the modified perovskite quantum dot/amino carbon quantum dot solution, and stirring for reaction for 0.5-1 h to obtain a dispersion liquid A;

s102: adding hydroxyapatite and tetracalcium phosphate into the dispersion liquid A, soaking and adsorbing for 3-6 hours, and fully stirring to obtain dispersion liquid B;

s103: and (3) adding hydroxypropyl chitosan and sodium alginate into the B dispersed slurry, stirring and reacting for 2-4 h at 45-60 ℃, then dropwise adding a calcium chloride solution, and continuously stirring and crosslinking for 0.5-2 h to obtain the bone defect repairing material.

Technical Field

The invention belongs to the field of biomedical materials, and particularly relates to a bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots and a preparation method thereof.

Background

Bone defects are a shortage of bone mass caused during pathological or surgical procedures, such that the structural integrity of the bone is compromised. Clinically, bone defects may be caused by trauma, tumor, osteomyelitis, various congenital diseases, surgical operations, and the like. Due to the presence of bone defects, nonunion, delayed or no healing of the resulting bone, and localized dysfunction are often caused. At present, methods for treating bone defects include autologous bone and allogeneic bone transplantation, a tissue engineering technology, a gene therapy rejection method, a physical factor therapy and the like, but the autologous bone transplantation can cause secondary trauma, the allogeneic bone transplantation can cause an immune rejection phenomenon, the tissue engineering technology and the gene therapy rejection method are still in a laboratory stage, the clinical application difficulty is high, and the physical factor therapy is adjuvant therapy and is mainly used for later-stage rehabilitation. Therefore, various bionic bone repair materials are produced to meet the requirements of clinical application.

The bone repair material is a novel bone repair material which is artificially synthesized, is self-cured and molded, has high mechanical strength, convenient use and biological characteristics (no toxic or side effect, absorption and degradation, good biocompatibility, capability of inducing the growth of osteocytes and blood vessels and the like). The bone repair material is mainly compounded by biological ceramic particles such as hydroxyapatite, bioactive glass, nano alumina and the like and gelatin, chitosan, polylactic acid or polyglycolic acid and the like, has the capability of promoting the growth of bone tissues and realizing osseointegration, and can be degraded after new bones are regenerated for replacement and repair. However, after the bone repair material is implanted into damaged bone tissues, how to track and monitor the positioning and differentiation conditions of bone stem cells and mesenchymal stem cells of bone marrow and the problem of repairing bone tissues are still difficult in clinical application.

The perovskite quantum dot serving as a semiconductor material has the characteristics of simplicity in synthesis, narrow emission peak, high fluorescence quantum efficiency, adjustable luminescence peak position and the like, has huge biological imaging advantages, and has application prospects in the fields of light-emitting diodes, biological markers, fluorescence detection and the like. However, perovskite quantum dots are highly sensitive to the environment due to strong ionic property, high surface energy and metastable structure, and are easy to cause phase transition, agglomeration and even degradation under the action of polar solvent or water and oxygen, thereby causing fluorescence quenching, especially Sn²⁺Is B-site element, and is easily oxidized into Sn in humid air⁴⁺The main defects of halogen vacancies and interstitial metals are intensified, and the collapse of the perovskite structure is further accelerated. Due to the poor stability of perovskite quantum dots, the practical application thereof is greatly limited.

Based on the above, the bone defect repairing material with a fluorescence detection effect is prepared by using the modified perovskite quantum dots/amino carbon quantum dots with high stability and biological safety for the first time.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots and a preparation method thereof.

The technical scheme of the invention is summarized as follows:

a bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following raw materials in parts by mass:

the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following raw materials in parts by mass: 0.5-1 part of perovskite quantum dots, 0.6-1.2 parts of amino carbon quantum dots, 8-16 parts of phosphatidylserine, 3-5 parts of citric acid, 1-3 parts of reduced glutathione, 0.5-1 part of EDC & HCl, 20-30 parts of chloroform and 100 parts of deionized water; the preparation method of the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following steps:

i: adding phosphatidylserine into a chloroform solvent, magnetically stirring until the phosphatidylserine is completely dissolved, then adding the perovskite quantum dots, uniformly stirring, and carrying out rotary evaporation at the temperature of 60-70 ℃ to remove chloroform, thus obtaining the perovskite quantum dot lipid film;

ii: adding citric acid and reduced glutathione into deionized water, stirring and dissolving, then adding amino carbon quantum dots, and stirring and reacting at 40-50 ℃ for 1-2 hours to obtain an amino carbon quantum dot reaction solution;

iii: and adding the perovskite quantum dot lipid film into the obtained amino carbon quantum dot reaction liquid, stirring and dispersing, then heating to 50-60 ℃, adding EDC & HCl, and continuously stirring and reacting for 2-4 hours to obtain the modified perovskite quantum dot/amino carbon quantum dot solution.

Preferably, the perovskite quantum dots comprise CsPbCl₃、CsPbBr₃、CsPbI₃、CsPbBr_3-xCl_x、CsPbBr_3-xI_x、CsSnCl₃、CsSnBr₃、CsSnI₃、CsSnBr_3-xCl_x、CsSnBr_3-xI_xOne or more of (a).

Preferably, 0 < x < 3.

Preferably, the mass concentration of the calcium chloride solution is 0.5-1%.

A preparation method of a bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following steps:

s101: adding bone growth factors, collagen and chondroitin sulfate into the modified perovskite quantum dot/amino carbon quantum dot solution, and stirring for reaction for 0.5-1 h to obtain a dispersion liquid A;

s102: adding hydroxyapatite and tetracalcium phosphate into the dispersion liquid A, soaking and adsorbing for 3-6 hours, and fully stirring to obtain dispersion liquid B;

s103: and (3) adding hydroxypropyl chitosan and sodium alginate into the B dispersed slurry, stirring and reacting for 2-4 h at 45-60 ℃, then dropwise adding a calcium chloride solution, and continuously stirring and crosslinking for 0.5-2 h to obtain the bone defect repairing material.

The invention has the beneficial effects that:

1. according to the invention, perovskite quantum dots and amino carbon quantum dots are introduced into a bone defect repairing material for the first time, the calcium titanium quantum dots and the amino carbon quantum dots are utilized to mediate the transfection of bone stem cells and bone marrow mesenchymal stem cells, the stem cell positioning and differentiation conditions are monitored by a fluorescence microscopic imaging technology, and the whole process of repairing a defect bone tissue part is tracked and monitored; meanwhile, stem cells are induced to differentiate towards osteoblasts and chondroblasts, and the proliferation and regeneration of the osteocytes are stimulated.

2. The method for treating the perovskite quantum dots and the amino carbon quantum dots by combining the phosphatidylserine, the citric acid and the reduced glutathione for the first time improves the stability and the biological safety of the quantum dots, coats the perovskite quantum dots with the phosphatidylserine to form the quantum dot liposome, and avoids the perovskite quantum dots and O₂Directly contacting with polar solvent to improve the fluorescence stability of perovskite quantum dots, and using-NH₂and-COOH, so that citric acid and reduced glutathione are further modified on the surfaces of the quantum dot liposome and the amino carbon quantum dot, and both the citric acid and the reduced glutathione have reducibility, oxygen free radicals are removed, the B-site metastable element of the perovskite quantum dot is further prevented from being oxidized, the collapse of the perovskite structure is avoided, the fluorescence quantum efficiency is improved, and meanwhile, the citric acid also has excellent metal chelating property and fixes free metal ions Pb²⁺、Sn²⁺Further improving the biological safety.

3. The invention takes hydroxyapatite and tetracalcium phosphate as the skeleton structure of the bone defect repair material and as the carriers of active components such as quantum dots, growth-like protein and the like, and the hydroxyapatite and the tetracalcium phosphate utilize the static between the hydroxyapatite and the tetracalcium phosphate and bone growth factors, collagen, chondroitin sulfate, modified perovskite quantum dots/amino carbon quantum dotsThe active components such as quantum dots, growth-like proteins and the like are adsorbed on the surfaces of hydroxyapatite and tetracalcium phosphate by the action of electric attraction, hydrogen bonds and van der waals force to achieve the slow release effect, and meanwhile, the hydroxyapatite and the tetracalcium phosphate are enriched with a large amount of-COOH and-NH₂-COOH with-NH in hydroxypropyl chitosan₂-OH, -NH₂Reacts with-COOH in sodium alginate to form a mutually cross-linked network structure, thereby further improving the stability of the bone defect material and the drug slow-release effect.

4. The bone defect repairing material can effectively bond an interface of damaged bone tissues, participate in metabolic circulation of an organism, and has stimulation or induction effects on bone cell proliferation and bone tissues, thereby realizing the repair of the damaged bone tissues.

Drawings

FIG. 1 is a flow chart of a preparation method of a bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots.

Detailed Description

The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.

The preparation method of the amino carbon quantum dots in the following examples comprises the following steps: and (2) dissolving 1 part of citric acid and 10 parts of polyethyleneimine into 200 parts of deionized water according to parts by mass, placing the solution in a reaction kettle, carrying out hydrothermal reaction at 180 ℃ for 24 hours, dialyzing, and drying in vacuum to obtain the amino carbon quantum dot.

Example 1

A bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following raw materials in parts by mass:

the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following raw materials in parts by mass: CsSnCl₃0.5 part of perovskite quantum dot, 0.6 part of amino carbon quantum dot, 8 parts of phosphatidylserine, 3 parts of citric acid, 1 part of reduced glutathione, 0.5 part of EDC & HCl, and chlorine20 parts of imitation water and 100 parts of deionized water.

A preparation method of a bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following steps:

s101: preparing a modified perovskite quantum dot solution:

i: adding phosphatidylserine into chloroform solvent, magnetically stirring until completely dissolved, and adding CsSnCl₃Uniformly stirring the perovskite quantum dots, and then carrying out rotary evaporation at 60 ℃ to remove chloroform, thereby obtaining the perovskite quantum dot lipid film;

ii: adding citric acid and reduced glutathione into deionized water, stirring and dissolving, then adding amino carbon quantum dots, and stirring and reacting for 1h at 40 ℃ to obtain an amino carbon quantum dot reaction solution;

iii: adding the perovskite quantum dot lipid film into the obtained amino carbon quantum dot reaction liquid, stirring and dispersing, then heating to 50 ℃, adding EDC & HCl, and continuously stirring and reacting for 2 hours to obtain a modified perovskite quantum dot/amino carbon quantum dot solution;

s102: adding bone growth factors, collagen and chondroitin sulfate into the modified perovskite quantum dot/amino carbon quantum dot solution, and stirring for reaction for 0.5h to obtain a dispersion liquid A;

s103: adding hydroxyapatite and tetracalcium phosphate into the dispersion liquid A, soaking and adsorbing for 3 hours, and fully stirring to obtain dispersion liquid B;

s104: and adding hydroxypropyl chitosan and sodium alginate into the dispersed slurry B, stirring and reacting for 2 hours at 45 ℃, then dropwise adding a calcium chloride solution with the mass concentration of 0.5%, and continuously stirring and crosslinking for 0.5 hour to obtain the bone defect repairing material.

Example 2

A bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following raw materials in parts by mass:

modified perovskite quantum dot/amino carbon quantum dot solutionThe liquid comprises the following raw materials in parts by mass: CsSnBr₃0.8 part of perovskite quantum dot, 1.0 part of amino carbon quantum dot, 12 parts of phosphatidylserine, 4 parts of citric acid, 2 parts of reduced glutathione, 1 part of EDC & HCl, 25 parts of chloroform and 100 parts of deionized water.

A preparation method of a bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following steps:

s101: preparing a modified perovskite quantum dot solution:

i: adding phosphatidylserine into chloroform solvent, magnetically stirring until completely dissolved, and adding CsSnBr₃Uniformly stirring the perovskite quantum dots, and then carrying out rotary evaporation at 65 ℃ to remove chloroform, thereby obtaining the perovskite quantum dot lipid film;

ii: adding citric acid and reduced glutathione into deionized water, stirring and dissolving, then adding amino carbon quantum dots, stirring and reacting at 45 ℃ for 1.5h to obtain an amino carbon quantum dot reaction solution;

iii: adding the perovskite quantum dot lipid film into the obtained amino carbon quantum dot reaction liquid, stirring and dispersing, then heating to 55 ℃, adding EDC & HCl, and continuously stirring and reacting for 3 hours to obtain a modified perovskite quantum dot/amino carbon quantum dot solution;

s102: adding bone growth factors, collagen and chondroitin sulfate into the modified perovskite quantum dot/amino carbon quantum dot solution, and stirring for reacting for 1h to obtain a dispersion liquid A;

s103: adding hydroxyapatite and tetracalcium phosphate into the dispersion liquid A, soaking and adsorbing for 4.5 hours, and fully stirring to obtain dispersion liquid B;

s104: and adding hydroxypropyl chitosan and sodium alginate into the dispersed slurry B, stirring and reacting for 3h at 55 ℃, then dropwise adding a calcium chloride solution with the mass concentration of 0.8%, and continuously stirring and crosslinking for 1h to obtain the bone defect repairing material.

Example 3

A bone defect repairing material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following raw materials in parts by mass:

the modified perovskite quantum dot/amino carbon quantum dot solution comprises the following raw materials in parts by mass: CsSnI₃1 part of perovskite quantum dot, 1.2 parts of amino carbon quantum dot, 16 parts of phosphatidylserine, 5 parts of citric acid, 3 parts of reduced glutathione, 1 part of EDC & HCl, 30 parts of chloroform and 100 parts of deionized water.

A preparation method of a bone defect repair material based on modified perovskite quantum dots/amino carbon quantum dots comprises the following steps:

s101: preparing a modified perovskite quantum dot solution:

i: adding phosphatidylserine into chloroform solvent, magnetically stirring until completely dissolved, and adding CsSnI₃Uniformly stirring the perovskite quantum dots, and then carrying out rotary evaporation at 70 ℃ to remove chloroform, thereby obtaining the perovskite quantum dot lipid film;

ii: adding citric acid and reduced glutathione into deionized water, stirring and dissolving, then adding amino carbon quantum dots, stirring and reacting for 2 hours at 50 ℃ to obtain amino carbon quantum dot reaction liquid;

iii: adding the perovskite quantum dot lipid film into the obtained amino carbon quantum dot reaction liquid, stirring and dispersing, then heating to 60 ℃, adding EDC & HCl, and continuously stirring and reacting for 4 hours to obtain a modified perovskite quantum dot/amino carbon quantum dot solution;

s102: adding bone growth factors, collagen and chondroitin sulfate into the modified perovskite quantum dot/amino carbon quantum dot solution, and stirring for reacting for 1h to obtain a dispersion liquid A;

s103: adding hydroxyapatite and tetracalcium phosphate into the dispersion liquid A, soaking and adsorbing for 6 hours, and fully stirring to obtain dispersion liquid B;

s104: and adding hydroxypropyl chitosan and sodium alginate into the B dispersed slurry, stirring and reacting for 4 hours at 60 ℃, then dropwise adding a calcium chloride solution with the mass concentration of 1%, and continuously stirring and crosslinking for 2 hours to obtain the bone defect repairing material.

Comparative example 1 is the same as example 1 except that the raw material of the quantum dot solution does not contain amino carbon quantum dots.

Comparative example 2 is the same as example 1, except that the raw materials and the parts by mass of the quantum dot solution are as follows: 0.6 part of amino carbon quantum dots, 3 parts of citric acid, 1 part of reduced glutathione, 0.5 part of EDC & HCl and 100 parts of deionized water; the preparation method comprises the following steps: adding citric acid and reduced glutathione into deionized water, stirring for dissolving, adding amino carbon quantum dots, stirring at 40 deg.C for reaction for 1h, heating to 50 deg.C, adding EDC & HCl, and stirring for reaction for 2 h.

Comparative example 3 is the same as example 1 except that the modified perovskite quantum dot/amino carbon quantum dot solution is replaced with deionized water.

The bone defect repairing materials prepared in examples 1-3 and comparative examples 1-2 can photoluminescence under the irradiation of excitation light of 320-500 nm, stem cells can be labeled by using the fluorescence property of the bone defect repairing materials, and the behavior change of the stem cells can be monitored, while the repairing material prepared in comparative example 3 has no luminescence property. The luminescent properties of the bone defect repair materials prepared in examples 1 to 3 and comparative examples 1 to 2 were measured, and the test results are shown in table 1:

table 1:

	example 1	Example 2	Example 3	Comparative example 1	Comparative example 2
						Luminescence quantum yield/%)	93.2	93.6	93.5	91.8	38.6
Quantum dot fluorescence lifetime/ns	20.6	20.8	20.6	17.2	4.1

Embodiments 1 to 3 introduce perovskite quantum dots and amino carbon quantum dots into a bone defect repair material for the first time, mediate transfection of bone stem cells and bone marrow mesenchymal stem cells by the perovskite quantum dots and the amino carbon quantum dots, monitor stem cell positioning and differentiation conditions by a fluorescence microscopic imaging technology, and realize tracking and monitoring of the whole process of repairing a defect bone tissue part; meanwhile, stem cells are induced to differentiate towards osteoblasts and chondroblasts, and the proliferation and regeneration of the osteocytes are stimulated.

Examples 1 to 3 perovskite quantum dots and amino carbon quantum dots were first treated with phosphatidylserine, citric acid, and reduced glutathione, to improve the stability and biosafety of the quantum dots, and the perovskite quantum dots were coated with phosphatidylserine to form quantum dot liposomes, thereby avoiding the perovskite quantum dots and O₂Directly contacting with polar solvent to improve the fluorescence stability of perovskite quantum dots, and using-NH₂and-COOH to further modify the citric acid and the reduced glutathione on the surfaces of the quantum dot liposome and the amino carbon quantum dot, wherein the citric acid and the reduced glutathione areThe glycomacropeptide has reducibility, oxygen free radicals are eliminated, the B-site metastable state element oxidation of the perovskite quantum dot is further prevented, the collapse of the perovskite structure is avoided, the fluorescence quantum efficiency is improved, and meanwhile, the citric acid also has excellent metal chelating property and fixes free metal ions Pb²⁺、Sn²⁺Further improving the biological safety.

Examples 1 to 3 use hydroxyapatite and tetracalcium phosphate as the skeleton structure of bone defect repair material and as the carriers of active ingredients such as quantum dots and growth-like proteins, and the hydroxyapatite and tetracalcium phosphate utilize the electrostatic attraction, hydrogen bonds and van der waals force between the hydroxyapatite and tetracalcium phosphate and bone growth factors, collagen, chondroitin sulfate, modified perovskite quantum dots/amino carbon quantum dots to make the active ingredients such as quantum dots and growth-like proteins adsorbed on the surfaces of the hydroxyapatite and tetracalcium phosphate, thereby achieving the slow release effect and simultaneously enriching the hydroxyapatite and tetracalcium phosphate with a large amount of-COOH and-NH₂-COOH with-NH in hydroxypropyl chitosan₂-OH, -NH₂Reacts with-COOH in sodium alginate to form a mutually cross-linked network structure, thereby further improving the stability of the bone defect material and the drug slow-release effect.

The bone defect repair materials of the embodiments 1 to 3 can effectively bond with the interface of the damaged bone tissue, participate in the metabolic cycle of the organism, and have stimulation or induction effects on the proliferation of bone cells and the bone tissue, thereby realizing the repair of the defective bone tissue.

While embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.