Chiral bone cement, preparation method therefor, and use thereof

Abstract

The present invention relates to the field of biomedical materials, and in particular to bone cement having good adhesion, good solidification, and chirality, a preparation method therefor, and a use thereof. According to the present invention, by means of introduction of a chiral molecule-modified polysaccharide, a chiral bone cement which implements construction of an adaptive chiral microenvironment, has strong connection and integration fastness with an organism bone, can be rapidly cured, and finally implements immediate implantation is prepared.

Description

Chiral bone cement and its preparation method and application Technical Field

[0001] The present invention belongs to the field of biomedical materials, and specifically relates to a bone cement with good adhesion, good curing and a chiral multi-level structure, as well as a preparation method and application thereof. Background Art

[0002] On a macroscopic level, bone is the body's hardest tissue, supporting the body and enabling movement in collaboration with skeletal muscle and the nervous system. On a microscopic level, skeletal tissue exhibits distinct developmental patterns and cellular composition characteristics depending on its location. The various cells within bone have the ability to sense mechanical stimuli and convert them into biological signals. Bone defects are bone defects caused by trauma or surgery, often resulting in nonunion, delayed healing or nonunion, and localized dysfunction. Bone defects caused by pathological processes, such as comminuted fractures and open fractures resulting from trauma, inflammation, and bone disease, large bone tissue defects due to necrosis and separation caused by inflammation, and defects caused by large areas of bone necrosis due to bone infarction or avascular necrosis, are all considered bone defects caused by disease.

[0003] Currently, autologous bone or allogeneic bone transplantation is the most commonly used method for treating bone defects. Autologous bone is currently recognized as the best method for repairing bone defects, primarily due to its excellent osteoconductivity, osteoinductivity, and biocompatibility. However, its limited availability, invasive bone harvesting process, and high donor site complications limit its application. Although allogeneic bone is abundant and readily available, it lacks the osteoinductivity and osteogenic properties of autologous bone, and carries the risk of disease transmission and immune rejection. Although tissue has a certain regenerative capacity, its repair capacity is relatively weak in large bone defects, and the extent of the defect exceeds the natural repair capacity of bone. Therefore, clinical intervention is often required to promote bone tissue repair. Traditional treatments for large bone defects mainly include vascularized fibula transplantation, open bone grafting (Papineau technique), and bone transport (Ilizarov technique). However, these techniques have long treatment cycles, high technical requirements, and are prone to complications such as fracture nonunion, limiting their clinical application. Due to the limited source of autologous bone and the risk of rejection and infection of allogeneic bone, the preparation of bionic bone scaffolds to maximize the promotion of bone tissue repair has always been a research hotspot in clinical medicine and materials science. Bioscaffolds have gradually become a promising biomaterial for bone repair and regeneration.

[0004] Ideal bone repair materials should possess excellent biocompatibility, be non-toxic or have low toxicity to the human body, be easily molded to meet the needs of different implant sites, possess a suitable microstructure to ensure tissue ingrowth and nutrient supply, and be capable of gradual degradation and replacement by new bone in the body. Bone cement, a member of the bone repair biomaterial family, self-solidifies through physical and chemical reactions between solid and liquid phases. Bone cement can be delivered to the target site through a small surgical incision, or even percutaneous injection, simplifying and minimizing treatment and promoting patient recovery. In the 1980s, Drs. Brown and Chow investigated remineralizing pastes for repairing early-stage dental caries and developed calcium phosphate cement (CPC). This material, composed of a solid phase composed of one or more calcium phosphate compounds and a liquid phase, is homogenized into a slurry. Under physiological conditions, it solidifies through chemical reactions and ultimately bioconverts to hydroxyapatite (HAP) in the body. Due to its excellent fluidity, low heat release during curing, osteoconductivity, biocompatibility, degradability, and drug-carrying properties, CPC has significant application value in bone repair. However, the solid phase used in the existing preparation of calcium phosphate bone cement is powder or particles with a common structure. The bone cement formed by powder or particles with a common structure does not have biocompatibility, especially structural compatibility, which is an important factor in designing biomaterials, resulting in unsatisfactory treatment effects.

[0005] In Chinese patent CN115364276B, a composite calcium phosphate bone cement loaded with erythrosin polysaccharide is disclosed. The preparation method thereof is as follows: mixing the solid phase of the bone cement, dissolving a certain amount of erythrosin polysaccharide in the liquid phase of the bone cement, placing the solid phase and the liquid phase in a constant temperature water bath at 80-95°C according to a liquid-solid ratio of 0.6-1.5 mL / g, stirring continuously for gelatinization, and then shaping and solidifying. However, the microstructure of the bone tissue is ignored, and for patients with bone defects, immediate implantation cannot be achieved. For another example, in Chinese patent CN114105114B, a method for preparing a chiral mesostructured hydroxyapatite film with a simple process, low cost, multi-level chiral structure and good biocompatibility is disclosed. The film is used as a cell culture matrix material, a stem cell differentiation induction material, a stem cell selective differentiation induction matrix or a carrier of a targeted drug. However, for patients with bone defects, immediate implantation is still not possible.

[0006] Therefore, biocompatible biomaterials are key to the field of tissue repair, reconstruction and regeneration. The structures of biomaterials, such as pores, surface roughness, and topology, are important factors in bioadaptability. Therefore, regulating the structure of materials can produce biomaterials with good adaptability and excellent performance. Chirality is a basic property of nature, commonly present in organisms, and closely related to life activities, such as various helical structures of DNA, proteins, cells and tissues. Multi-level structures are a common phenomenon in nature. Because materials have multi-level organizational structures, this gives them unexpected properties. Natural bone is a chiral multi-level structure.

[0007] Living organisms themselves are chiral multi-level structures that exhibit specific selectivity for chiral environments. For example, chiral drugs exert different effects within living organisms, with thalidomide being the most typical example. Some chiral pesticides also exhibit varying insecticidal properties. Currently, the relationship between chiral substances and living organisms has become a hot topic of research. The present invention, during the preparation of bone cement, achieves the construction of a chiral multi-level structure with an adaptive microenvironment by adding chiral molecules, polysaccharide derivatives, dopamine, and organic acids, resulting in excellent curing strength, strong adhesion, and the ability to be immediately implanted.

[0008] Summary of the Invention

[0009] The present invention utilizes non-toxic, biodegradable, and absorbable chiral molecules to modify polysaccharides, which can induce the in situ formation of a chiral, hierarchical microenvironment during the hydration process of bone cement. Furthermore, the polysaccharide derivative in the liquid phase ionizes in an acidic environment, enhancing its ability to chelate calcium ions, thereby generating adhesion at the chemical bond level. Furthermore, the polysaccharide derivative co-modified with dopamine and chiral molecules mimics the adhesive molecules found in mussel protein, generating adhesion at the hydrogen bond level. Consequently, the chiral bone cement prepared by the present invention achieves the construction of an adaptive chiral microenvironment, a strong, integrated connection between the implant and the bone, and rapid curing properties.

[0010] In a first aspect, the present invention provides a chiral bone cement obtained by a hydration and solidification reaction between a solid phase and a liquid phase, wherein the liquid phase component of the bone cement contains an acidic aqueous solution of a chiral polysaccharide derivative, and the solid phase component of the bone cement contains a calcium-based bioceramic material. The bone cement has the characteristics of adhesion and rapid solidification.

[0011] Furthermore, the calcium-based bioceramic material includes but is not limited to hydroxyapatite, β-tricalcium phosphate, calcium silicate, calcium borate, calcium carbonate, calcium sulfate, calcium dihydrogen phosphate and / or other calcium phosphates.

[0012] In some embodiments, the calcium-based bioceramic material is selected from β-tricalcium phosphate and monocalcium phosphate, wherein the ratio of β-tricalcium phosphate to monocalcium phosphate is 1:0.5-1.

[0013] Furthermore, the acidic aqueous solution of the chiral polysaccharide derivative is obtained by the following steps:

[0014] S001. The chiral molecule is dissolved in a solution, and then the polysaccharide is added, stirred to dissolve, heated, and crystallized to form a mixed solution A;

[0015] S002. Dopamine is added to the mixed solution A to form a mixed solution B;

[0016] S003. The polysaccharide is dissolved in an acidic solution and stirred thoroughly to form a mixed solution C;

[0017] S004. Mix solution B and solution C in proportion to obtain a final liquid phase, which is an acidic aqueous solution of the chiral polysaccharide derivative.

[0018] Furthermore, the liquid phase may be a D-type or L-type chiral liquid phase depending on the configuration of the selected chiral molecules.

[0019] Furthermore, the chiral molecule is one or more of chiral amino acids, polypeptide molecules, protein molecules, chiral organic acids, chiral sugars and chiral alcohols.

[0020] Furthermore, the chiral amino acid is one or more of histidine, arginine, lysine, isoleucine, phenylalanine, leucine, tryptophan, alanine, methionine, proline, cysteine, aspartic acid, valine, serine, glutamine, tyrosine, aspartic acid, glutamic acid, and threonine; the polypeptide molecule is diphenylalanine; the protein molecule is bovine serum albumin or soluble collagen; the chiral organic acid is one or more of tartaric acid, malic acid, and lactic acid; the chiral sugar is one or more of glucose, fructose, galactose, ribose, deoxyribose, furanose, pyranose, maltose, sucrose, lactose, and hyaluronic acid; and the chiral alcohol is one or more of mannitol, xylitol, sorbitol, paclitaxel, resveratrol, ginkgo biloba polyprenol, (R)-(+)-1-phenyl-1-propanol, (S)-(-)-1-phenyl-1-propanol, and phenylpropanol.

[0021] Furthermore, the polysaccharide includes but is not limited to one or more of starch, cellulose starch, cellulose, gum arabic, pectin, galactose, chitin (chitin), polyfructose, agar, hyaluronic acid, chondroitin sulfate, dermatan sulfate, laminar acid sulfate, heparin, heparan sulfate, and alginic acid.

[0022] Furthermore, the polysaccharide derivatives include, but are not limited to, one or more of cellulose derivatives, amylose derivatives, xylan derivatives, inulin derivatives, deacetylated chitosan derivatives, and glucose derivatives.

[0023] Furthermore, the acidic solution includes but is not limited to one or more of oxalic acid, citric acid, acetic acid, carbonic acid, hydrofluoric acid, succinic acid, malic acid, gluconic acid, formic acid, lactic acid, benzoic acid, acrylic acid, propionic acid, stearic acid, hydrosulfuric acid, hypochlorous acid, and boric acid.

[0024] Furthermore, the mass ratio of the chiral molecule to the polysaccharide is 3-10:1-3.

[0025] Furthermore, the amount of added dopamine is 10-20 mg / mL.

[0026] Furthermore, the amount of acid added to the acidic solution is 2 wt% to 50 wt%.

[0027] Furthermore, the ratio of solution B to solution C is 1-4:1-2.

[0028] Furthermore, the ratio of the liquid phase to the solid phase of the chiral bone cement is 1:0.2-1 (mass g / volume mL).

[0029] Furthermore, metal ions can be added to the liquid phase as antibacterial or osteogenesis-promoting functional elements of bone cement.

[0030] Furthermore, the metal ions include but are not limited to Sr 2+ 、Zn 2+ 、Mn 2+ 、Ga 2+ 、Zn 2+ 、Ag 3+ One or more of .

[0031] In a second aspect, the present invention provides a method for preparing the chiral bone cement as described in the first aspect, the method comprising the following steps:

[0032] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0033] Step S2: selecting a calcium-based bioceramic material as the solid phase of bone cement;

[0034] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are subjected to a hydration curing reaction to obtain an adhesive fast-curing chiral bone cement.

[0035] Furthermore, the bone cement liquid phase in step S1 is obtained by the following steps:

[0036] S001. The chiral molecule is dissolved in a solution, and then the polysaccharide is added, stirred to dissolve, heated, and crystallized to form a mixed solution A;

[0037] S002. Dopamine is added to the mixed solution A to form a mixed solution B;

[0038] S003. The polysaccharide is dissolved in an acidic solution and stirred thoroughly to form a mixed solution C;

[0039] S004. Mix solution B and solution C in proportion to obtain a final liquid phase, which is an acidic aqueous solution of the chiral polysaccharide derivative.

[0040] Furthermore, the mass ratio of the chiral molecule to the polysaccharide is 3-10:1-3.

[0041] Furthermore, the amount of added dopamine is 10-20 mg / mL.

[0042] Furthermore, the amount of acid added to the acidic solution is 2 wt% to 50 wt%.

[0043] Furthermore, the ratio of solution B to solution C is 1-4:1-2.

[0044] Furthermore, the ratio of the liquid phase to the solid phase of the chiral bone cement is 1:0.2-1 (mass g / volume mL).

[0045] Furthermore, metal ions can be added to the liquid phase as antibacterial or osteogenesis-promoting functional elements of bone cement.

[0046] Furthermore, the metal ions include but are not limited to Sr 2+ 、Zn 2+ 、Mn 2+ 、Ga 2+ 、Zn 2+ 、Ag 3+ One or more of .

[0047] In a third aspect, the present invention provides an application of the chiral bone cement as described in the first aspect in the preparation of medical biomaterials for treating bone defects, wherein the application is the application in the preparation of bone cement that improves curing performance, promotes bone chelation, and promotes bone regeneration and bone healing ability.

[0048] Furthermore, the bone defect refers to the loss of normal bone due to various reasons.

[0049] Furthermore, the bone defect includes but is not limited to one or more of traumatic bone defect, congenital bone defect, and infectious bone defect.

[0050] Furthermore, the bone defect includes but is not limited to alveolar bone defect, skull defect, femoral head necrosis defect, tumor bone necrosis defect, spinal bone defect, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG1 is a flow chart of the preparation of adhesive chiral bone cement;

[0052] FIG2 shows the viscosity of adhesive chiral bone cement;

[0053] Figure 3: Adhesive chiral bone cement fills and solidifies at the defect site in a pig bone defect model;

[0054] Figure 4 shows the porosity of the adhesive chiral bone cement in the pig bone defect model after filling and curing the defect for 30 minutes.

[0055] FIG5 shows the chiral signal of the adhesive chiral bone cement prepared in Example 1. DETAILED DESCRIPTION

[0056] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments, but they are not intended to limit the present invention. The embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other unless they conflict.

[0057] To make the objects, advantages, and features of the present invention more clearly apparent, the adhesive chiral bone cement and its preparation method proposed by the present invention are described in further detail below. It should be noted that the accompanying drawings are all in a very simplified form and use very precise proportions, and are only used to conveniently and clearly assist in illustrating the purpose of the embodiments of the present invention.

[0058] Example 1: Chiral bone cement product 1

[0059] The bone cement product of this embodiment is prepared by the following method (see Figure 1), and the steps of the method are as follows:

[0060] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0061] S001. Dissolve chiral L-tartaric acid in pure water, then add chitin at a mass ratio of 7.5:2. Stir thoroughly to dissolve the mixture, then heat to 30°C and continue stirring for 6 hours to allow for thermal crystallization, forming a mixed solution A.

[0062] S002. 10 mg / mL of dopamine was added to the mixed solution A, stirred for 10 minutes and irradiated with UV light for 2 minutes to form a mixed solution B;

[0063] S003. The chitosan was dissolved in a 40wt% citric acid solution and stirred thoroughly to dissolve to form a mixed solution C;

[0064] S004. Mix solution B and solution C in a volume ratio of 3:2 and stir at room temperature for 20 minutes to obtain a liquid phase of bone cement.

[0065] Step S2: selecting β-tricalcium phosphate and calcium dihydrogen phosphate in a mass ratio of 1:0.67 as the solid phase of bone cement;

[0066] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are hydrated and cured at a ratio of 1:0.33 mass g / volume mL to obtain an adhesive fast-curing chiral bone cement.

[0067] Similarly, D-tartaric acid can be selected as the chiral molecule to finally obtain D-type chiral bone cement.

[0068] The results are shown in Figures 2 to 5. Figure 2 shows the viscosity of the adhesive chiral bone cement of this example. The figure shows that the chiral bone cement is as sticky as chewing gum, which is sticky and can be drawn into threads. Figure 3 shows the filling and curing of the adhesive chiral bone cement at the defect site in a porcine bone defect model. The figure shows that the mixed bone cement is quickly formed and completely fills the defect area after filling the bone defect site. Figure 4 shows the perforation properties of the adhesive chiral bone cement at the defect site in the porcine bone defect model after 30 minutes of filling and curing. The figure shows that after 30 minutes of curing reaction, the bone cement has reached a considerable strength and can be perforated at the filled site. The obtained holes are uniform, stable, and have a good shape without cracking. Figure 5 shows the circular dichroism spectral signal, i.e., the chiral signal, of the prepared adhesive chiral bone cement. The figure shows the CD spectrum of the chiral bone cement formed by the polysaccharide modified with L-tartaric acid. It can be seen that there are two negative bulge peaks in the 200-800 nanometer band, corresponding to the different levels of chiral structure within the chiral bone cement.

[0069] Example 2: Chiral bone cement product 2

[0070] The bone cement product of this embodiment is prepared by the following method, and the steps of the method are as follows:

[0071] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0072] S001. Dissolve chiral L-malic acid in pure water, then add chitin in a ratio of 3:1 by weight. Stir thoroughly to dissolve the chitin. Then, heat to 40°C and continue stirring for 5 hours to allow for thermal crystallization, forming a mixed solution A.

[0073] S002. 15 mg / mL of dopamine was added to the mixed solution A, stirred for 5 minutes and irradiated with UV light for 6 minutes to form a mixed solution B;

[0074] S003. The chitosan was dissolved in a 30wt% citric acid solution and stirred thoroughly to form a mixed solution C;

[0075] S004. Mix solution B and solution C in a volume ratio of 1:1, and stir at room temperature for 60 minutes to obtain a liquid phase of bone cement.

[0076] Step S2: selecting β-tricalcium phosphate and calcium dihydrogen phosphate in a mass ratio of 1:0.67 as the solid phase of bone cement;

[0077] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are hydrated and cured at a ratio of 1:0.4 mass g / volume mL to obtain an adhesive fast-curing chiral bone cement.

[0078] Similarly, D-malic acid can be selected as the chiral molecule to finally obtain D-type chiral bone cement.

[0079] Example 3 Chiral bone cement product 3

[0080] The bone cement product of this embodiment is prepared by the following method, and the steps of the method are as follows:

[0081] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0082] S001. Dissolve chiral L-tartaric acid in pure water, then add chitin at a mass ratio of 4:1. Stir thoroughly to dissolve the mixture, then heat to 50°C and continue stirring for 4 hours to allow for thermal crystallization, forming a mixed solution A.

[0083] S002. 20 mg / mL of dopamine was added to the mixed solution A, stirred for 10 minutes and irradiated with UV light for 3 minutes to form a mixed solution B;

[0084] S003. The chitosan was dissolved in a 20wt% oxalic acid solution and stirred thoroughly to form a mixed solution C;

[0085] S004. Mix solution B and solution C in a volume ratio of 4:1, and stir at room temperature for 40 minutes to obtain a liquid phase of bone cement.

[0086] Step S2: selecting β-tricalcium phosphate and calcium dihydrogen phosphate in a mass ratio of 1:0.5 as the solid phase of bone cement;

[0087] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are hydrated and cured at a ratio of 1:0.25 g / mL to obtain an adhesive fast-curing chiral bone cement.

[0088] Similarly, D-tartaric acid can be selected as the chiral molecule to finally obtain D-type chiral bone cement.

[0089] Example 4 Chiral bone cement product 4

[0090] The bone cement product of this embodiment is prepared by the following method, and the steps of the method are as follows:

[0091] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0092] S001. Dissolve chiral L-aspartic acid in pure water, then add chitin at a mass ratio of 9:2. Stir thoroughly to dissolve the chitin. Then, heat to 60°C and continue stirring for 3 hours to allow for thermal crystallization, forming a mixed solution A.

[0093] S002. 12 mg / mL of dopamine was added to the mixed solution A, stirred for 8 minutes and irradiated with UV light for 2 minutes to form a mixed solution B;

[0094] S003. The chitosan was dissolved in a 20wt% oxalic acid solution and stirred thoroughly to form a mixed solution C;

[0095] S004. Mix solution B and solution C in a volume ratio of 2:1, and stir at room temperature for 80 minutes to obtain a liquid phase of bone cement.

[0096] Step S2: selecting β-tricalcium phosphate and calcium dihydrogen phosphate in a mass ratio of 1:0.75 as the solid phase of bone cement;

[0097] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are hydrated and cured at a ratio of 1:0.4 mass g / volume mL to obtain an adhesive fast-curing chiral bone cement.

[0098] Similarly, D-aspartic acid can be used as the chiral molecule to finally obtain D-type chiral bone cement.

[0099] Example 5 Chiral bone cement product 5

[0100] The bone cement product of this embodiment is prepared by the following method, and the steps of the method are as follows:

[0101] Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as the liquid phase of bone cement;

[0102] S001. Dissolve chiral L-glutamic acid in pure water, then add chitin in a ratio of L-aspartic acid to chitin of 5:1 by weight. Stir thoroughly to dissolve, then heat to 70°C and continue stirring for 1 hour to allow for thermal crystallization, forming a mixed solution A.

[0103] S002. 10 mg / mL of dopamine was added to the mixed solution A, stirred for 10 minutes and irradiated with UV light for 1 minute to form a mixed solution B;

[0104] S003. The chitosan was dissolved in a 2wt% acetic acid solution and stirred thoroughly to form a mixed solution C;

[0105] S004. Mix solution B and solution C in a volume ratio of 3:1, and stir at room temperature for 120 minutes to obtain a liquid phase of bone cement.

[0106] Step S2: selecting β-tricalcium phosphate and calcium dihydrogen phosphate in a mass ratio of 1:1 as the solid phase of bone cement;

[0107] Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are hydrated and cured at a ratio of 1:0.75 g / mL to obtain an adhesive fast-curing chiral bone cement.

[0108] Similarly, D-aspartic acid can be used as the chiral molecule to finally obtain D-type chiral bone cement.

[0109] Implementation of 6 chiral bone cement cell proliferation and adhesion experiments

[0110] In this test example, the D-type and L-type chiral bone cements of Example 1 were used to conduct cell adhesion, proliferation and differentiation experiments, and the cell lines used were bone marrow-derived mesenchymal stem cells (BMSCs).

[0111] The specific operation process of the adhesion and proliferation experiment is as follows:

[0112] 1) First, place the sterilized chiral bone cement on the bottom of the cell culture plate;

[0113] 2) Then, the dispersed BMSC cells are seeded on the chiral substrate and cultured;

[0114] 3) After a period of incubation, remove the culture plate, wash with PBS, and fix with 4% PFA;

[0115] 4) After fixation, wash several times with PBS and then stain;

[0116] 5) Finally, observe and take photos under a microscope.

[0117] The specific operation process of the differentiation experiment is as follows:

[0118] 1) First, bone marrow-derived mesenchymal stem cells were extracted from the femur of mice, cultured, and incubated;

[0119] 2) Then, implant the cells by placing the sterilized bone cement substrate on the bottom of the cell culture plate;

[0120] 3) seeding the dispersed BMSC cells on the chiral bone cement substrate and culturing them;

[0121] 3) After a period of incubation, remove the culture plate, wash with PBS, and fix with 4% PFA;

[0122] 4) After fixation, wash the sections several times with PBS and then perform Oil Red and ALP staining.

[0123] 5) Finally, observe and take photos under a microscope.

[0124] Implementation of 7 chiral bone cement implantation experiments in alveolar bone

[0125] In this test example, the D-type and L-type chiral bone cements of Example 1 were used to perform alveolar bone defect repair and immediate implantation experiments, and the animals used were beagle dogs.

[0126] The specific operation process is as follows:

[0127] 1) First, the alveolar bone defect model was created in beagle dogs;

[0128] 2) Implantation is then performed by first mixing the sterilized chiral bone cement evenly;

[0129] 3) The mixed bone cement is then filled into the alveolar bone defect and solidified in situ;

[0130] 4) After curing for a period of time, confirm whether the strength is enough to punch holes, then punch holes and implant screws, and then cultivate and repair for a period of time;

[0131] 5) Remove the sample and observe the bone defect repair.

Claims

1. A chiral bone cement, wherein the bone cement is obtained by hydration and solidification reaction of a solid phase and a liquid phase, wherein: The liquid phase component of the bone cement contains an acidic aqueous solution of a chiral polysaccharide derivative, and the solid phase component of the bone cement contains a calcium-based bioceramic material. The bone cement has the characteristics of adhesion and fast solidification.

2. The chiral bone cement according to claim 1, characterized in that: The calcium-based bioceramic material is selected from hydroxyapatite, β-tricalcium phosphate, calcium silicate, calcium borate, calcium carbonate, calcium sulfate, monocalcium phosphate and / or other calcium phosphates.

3. The chiral bone cement according to claim 1, characterized in that: The calcium-based bioceramic material is selected from β-tricalcium phosphate and monocalcium phosphate, wherein the ratio of β-tricalcium phosphate to monocalcium phosphate is 1:0.5-1.

4. The chiral bone cement according to claim 1, characterized in that: The acidic aqueous solution of the chiral polysaccharide derivative is obtained by the following steps: S001. The chiral molecule is dissolved in a solution, and then the polysaccharide is added, stirred to dissolve, heated, and crystallized to form a mixed solution A; S002. adding dopamine to the mixed solution A to form a mixed solution B; S003. Dissolving the polysaccharide in the acidic solution and stirring thoroughly to dissolve to form a mixed solution C; S004. Mix solution B and solution C in proportion to obtain a final liquid phase, which is an acidic aqueous solution of the chiral polysaccharide derivative.

5. The chiral bone cement according to claim 4, characterized in that: The mass ratio of the chiral molecule to the polysaccharide is 3-10:1-3.

6. The chiral bone cement according to claim 4, characterized in that: The ratio of the chiral bone cement liquid phase to the solid phase is 1:0.2-1 (mass g / volume mL).

7. The chiral bone cement according to claim 4, characterized in that: Metal ions can be added to the liquid phase as antibacterial or bone-forming functional elements of the bone cement, and the metal ions are selected from Sr 2+ 、Zn 2+ , Mn 2+ , Ga 2+ 、Zn 2+ 、Ag 3+ One or more of .

8. A method for preparing the chiral bone cement according to claim 1, comprising the following steps: Step S1: preparing an acidic aqueous solution containing a chiral polysaccharide derivative as a liquid phase of bone cement; Step S2: selecting a calcium-based bioceramic material as the solid phase of bone cement; Step S3: The solid phase of the bone cement obtained in step S2 and the liquid phase obtained in step S1 are subjected to a hydration curing reaction to obtain an adhesive fast-curing chiral bone cement.

9. The method for preparing chiral bone cement according to claim 8, characterized in that: The bone cement liquid phase in step S1 comprises the following steps to obtain: S001. The chiral molecule is dissolved in a solution, and then the polysaccharide is added, stirred to dissolve, heated, and crystallized to form a mixed solution A; S002. adding dopamine to the mixed solution A to form a mixed solution B; S003. Dissolving the polysaccharide in the acidic solution and stirring thoroughly to dissolve to form a mixed solution C; S004. Mix solution B and solution C in proportion to obtain a final liquid phase, which is an acidic aqueous solution of the chiral polysaccharide derivative.

10. Use of the chiral bone cement as claimed in claim 1 in the preparation of medical biomaterials for treating bone defects, wherein the application is the use of the chiral bone cement in the preparation of bone cements that improve curing performance, promote bone chelation, promote bone regeneration and bone healing ability.

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