Calcium sulfate-based biomimetic bone repair material, and preparation method and application thereof

Abstract

The application relates to the technical field of biomedical materials, in particular to a calcium sulfate-based bionic bone repair material and a preparation method and application thereof. The preparation method comprises the following steps: stirring and mixing calcium sulfate dihydrate mixture into a collagen solution; performing suction filtration on the mixed solution to obtain bone paste, and performing shaping and drying to obtain a pre-shaped bone block; heating the pre-shaped bone block under vacuum conditions to obtain a dehydrated bone block; and finally rehydrating the dehydrated bone block and solidifying under the condition that the relative humidity is greater than or equal to 90% to obtain a bone repair material; the calcium sulfate dihydrate mixture is composed of calcium sulfate dihydrate and inorganic particles. The material is densified through suction filtration, collagen cross-linking and the conversion of calcium sulfate dihydrate into calcium sulfate hemihydrate are simultaneously completed through vacuum heating, and then the rehydration and high-humidity solidification are performed to obtain a bone repair material with an interpenetrating network structure. The material has excellent mechanical properties, a controllable degradation rate and is suitable for bone defect repair.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a calcium sulfate-based biomimetic bone repair material and its preparation method and application. Background Technology

[0002] Bone defect repair is a common treatment need in clinical orthopedics, oral and maxillofacial surgery, and trauma surgery. Ideal bone repair materials should possess good biocompatibility, appropriate mechanical strength, a matched degradation rate, and excellent osteogenic induction activity. Currently, the materials most widely used and researched in clinical practice mainly include autologous bone, allogeneic bone, and artificial synthetic bone substitutes, but all of them have certain limitations: autologous bone has limited sources and is prone to secondary damage; allogeneic bone poses risks of immune rejection, disease transmission, and ethical issues; and traditional artificial bone materials struggle to achieve a harmonious match between mechanical support, degradation behavior, and the biomimetic microenvironment of bone tissue.

[0003] Calcium sulfate materials have been used for bone defect filling due to their wide availability, high biocompatibility, and certain osteoconductivity and early mechanical support. However, pure calcium sulfate materials have significant drawbacks: on the one hand, they are brittle and lack toughness, making them prone to breakage during surgery and resulting in poor clinical operability; on the other hand, they degrade too quickly, often degrading significantly before new bone tissue has fully ingrained, making it difficult to continuously provide a stable scaffold structure, thus limiting the later osteogenic effect.

[0004] Collagen is the main organic component of human bone tissue, possessing excellent cell adhesion, biocompatibility, and low immunogenicity, providing a biomimetic microenvironment for cell adhesion, proliferation, and differentiation. However, pure collagen raw materials have a loose structure and low mechanical strength, easily swelling and collapsing in physiological environments, and cannot independently provide the support required for bone defect repair. Existing bone repair materials composed of collagen and calcium-phosphorus-based inorganic phases mostly employ simple physical blending or conventional cross-linking molding methods, resulting in problems such as weak bonding between the organic and inorganic phases, significant phase separation, and poor structural uniformity. Furthermore, the cross-linking process often relies on chemical cross-linking agents or conventional thermal cross-linking, making it difficult to achieve stable cross-linking of collagen while simultaneously controlling the curing behavior of the inorganic phase. The material's toughness, structural stability, and clinical suitability still need improvement.

[0005] Furthermore, bone repair materials with a single degradation rate are difficult to match the bone tissue regeneration cycle. Excessive degradation leads to premature scaffold failure, while excessively slow degradation easily results in foreign body encapsulation, hindering new bone maturation. While there are reports of combining collagen, calcium sulfate, and components such as α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, or bioglass in existing composite systems, these generally suffer from problems such as cumbersome processes, low degree of organic phase fibrosis, uneven inorganic phase dispersion, and the inability to simultaneously achieve cross-linking of the organic phase and controllable curing of the inorganic phase. The biomimetic structure, mechanical properties, degradation coordination, and overall osteogenic effect of these materials still cannot fully meet the clinical needs for repairing complex bone defects. Therefore, developing a calcium sulfate-based composite bone repair material with a biomimetic structure, excellent mechanical properties, controllable degradation rate, good cell compatibility, and high osteogenic capacity has significant clinical value and research significance. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide a calcium sulfate-based biomimetic bone repair material, its preparation method and application, which has excellent biocompatibility, component ratio and structural design, can rapidly guide tissue regeneration, and can be completely degraded after implantation, thus meeting clinical needs.

[0007] The technical solution of this invention is implemented as follows: In a first aspect, the present invention proposes a method for preparing a calcium sulfate-based biomimetic bone repair material, comprising the following steps: S1. Add the calcium sulfate dihydrate mixture to the collagen solution and stir to mix to obtain a mixture; S2. Filter the mixture to obtain bone paste, place the bone paste in a mold to form it, and dry it to obtain pre-formed bone blocks; S3. The pre-formed bone block is heated under vacuum conditions to obtain a dehydrated bone block; S4. Rehydrate the dehydrated bone block and solidify it under conditions of relative humidity ≥90% to obtain bone repair material; The calcium sulfate dihydrate mixture comprises calcium sulfate dihydrate and inorganic particles, wherein the inorganic particles comprise at least one of α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, or bioglass.

[0008] Preferably, in step S1, the amount of the calcium sulfate dihydrate mixture added is 3 to 10 wt% of the collagen solution; the concentration of the collagen solution is 0.5 to 2.0 wt%.

[0009] Specifically, if the calcium sulfate dihydrate mixture is too small, it will be difficult to solidify on its own. As the main osteogenic component, a low content of calcium sulfate dihydrate mixture is not conducive to osteoogenesis. If the content of calcium sulfate dihydrate mixture is too large, it will lead to a relative reduction in collagen content. In terms of biomimicry, the difference in collagen content from that in bone tissue is too large, which is not conducive to cell adhesion and growth. In terms of mechanics, too little collagen cannot effectively cross-link in the subsequent cross-linking process, and thus cannot play a toughening role, resulting in mechanical properties that do not meet expectations.

[0010] Preferably, in the calcium sulfate dihydrate mixture in step S1, the calcium sulfate dihydrate accounts for 60-80 wt% of the total mass of the calcium sulfate dihydrate mixture.

[0011] Preferably, in step S1, the stirring and mixing is carried out at 25~35°C for 20~60 minutes.

[0012] Preferably, in step S2, the drying temperature is 30~45℃ and the time is 10~40h.

[0013] More preferably, in step S2, the filtration includes: filtration for 2 to 5 minutes under a vacuum of -0.08 to -0.1 MPa.

[0014] Preferably, in step S3, the heating temperature under vacuum conditions is 120~130℃, and the time is 10~20h.

[0015] Preferably, in step S4, the curing temperature is 30~45℃ and the time is 10~40h.

[0016] Preferably, the calcium sulfate dihydrate is a powder with a particle size ≤10μm; the inorganic particles are ceramic particles with a particle size of 0.25~1.0mm; and the collagen solution includes a type I collagen solution with telopeptides removed, and its pH value is 4~6.

[0017] More preferably, step S4 is followed by step S5: the bone repair material is packaged and then sterilized with ethylene oxide. Specifically, the bone repair material is packaged in a paper-plastic bag, and the sealing temperature is 150~170℃; the parameters for ethylene oxide sterilization include: temperature 37~40℃, humidity 50~70%, ethylene oxide concentration 600~800 mg / L, and exposure time 5~6h.

[0018] Secondly, the present invention provides a calcium sulfate-based biomimetic bone repair material obtained by the preparation method described in the first aspect.

[0019] Thirdly, the present invention provides an application of the calcium sulfate-based biomimetic bone repair material as described in the second aspect in the field of biomedical materials.

[0020] Compared with the prior art, the advantages of the present invention are as follows: (1) This invention fully utilizes the salting-out effect and isoelectric point characteristics of type I collagen solution. By adding calcium sulfate dihydrate, collagen is induced to self-assemble into fibers, and calcium sulfate dihydrate and inorganic particles are uniformly embedded in the collagen fiber network. At the same time, the salting-out and isoelectric point effects can significantly reduce the viscosity of the system, making it easier to concentrate the material through filtration and form a bone paste-like precursor with a certain plasticity, thereby achieving material densification and laying the foundation for subsequent molding and processing.

[0021] (2) In terms of structural construction, this invention can simultaneously achieve the cross-linking of collagen and the curing of calcium sulfate-based inorganic phases, forming a biomimetic organic-inorganic interpenetrating network structure of human bone: the collagen phase and inorganic phase are interwoven and integrated as a whole, significantly improving the mechanical properties and structural stability of the material; after vacuum cross-linking / dehydration treatment, the collagen completes cross-linking and curing, which can effectively bind inorganic particles inside the collagen network; at the same time, calcium sulfate dihydrate is dehydrated into calcium sulfate hemihydrate, giving the material curable properties. In clinical use, it can be pre-cured and molded before being implanted into the bone defect site, or it can be directly filled after rehydration and shaping, and cured in situ in vivo, which can adapt to a variety of clinical bone defect repair scenarios.

[0022] (3) In terms of component ratio and functional design, this invention achieves precise matching between degradation and osteogenicity through multi-component synergy. Although calcium sulfate material has good mechanical properties, its degradation rate is too fast and it is difficult to support osteogenicity in the later stage. This invention significantly improves the cell adhesion and biocompatibility of the material by introducing type I collagen. At the same time, collagen can effectively delay its degradation rate through fibrosis and cross-linking treatment. Further compounding with inorganic components such as β-tricalcium phosphate, hydroxyapatite or bioglass can regulate and slow down the degradation rate of the material as a whole, so that the material can maintain an intact scaffold structure in the middle and late stages of bone repair, continuously guide new bone ingrowth and tissue regeneration, and promote bone tissue crawling replacement and regeneration through multiple mechanisms, significantly improving the osteogenic effect. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is an appearance diagram of the bone repair material prepared in Example 1 of the present invention; Figure 2 The XRD curve of the bone repair material prepared in Example 1 of this invention; Figure 3The IR curve of the bone repair material prepared in Example 1 of this invention; Figure 4 HE-stained images of rat skull tissue collected 12 weeks after implantation of the bone repair material prepared in Example 1 of this invention; Figure 5 HE staining image of the bone repair material prepared in Comparative Example 1 of this invention after 12 weeks of rat skull implantation experiment. Detailed Implementation

[0025] The embodiments of the present invention are described in detail below. These embodiments are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0026] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0027] In this document, the terms “containing,” “comprising,” or “including” are open-ended expressions, meaning they include the contents specified in this invention but do not exclude other aspects.

[0028] In this document, the terms “optional,” “optionally,” or “optional” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0030] Unless otherwise specified, all reagents used in this invention can be purchased from the market.

[0031] The type I collagen solution used in this invention is prepared by the following method: Healthy beef Achilles tendons were selected as raw materials. Surface fascia, fat, and other impurities were removed, and the tendons were rinsed three times with deionized water and cut into small pieces. The cut tendons were then placed in a 0.9 wt% saline solution and soaked at 4°C for 24 hours, with the saline solution changed twice during this period to remove soluble impurities. Subsequently, 0.1 wt% (based on saline solution) of trypsin was added, and the mixture was enzymatically hydrolyzed at 4°C for 12 hours. After hydrolysis, the pH of the system was adjusted to 2.5 with 0.1 mol / L hydrochloric acid, and pepsin (hydrolysis ratio 1:100, g / g) was added. The mixture was then hydrolyzed at 37°C for 24 hours to obtain the desired product. The enzymatic hydrolysate was filtered through an 80-mesh filter cloth to remove insoluble residues. The solution was then slowly saturated with sodium chloride solution until the sodium chloride concentration reached 1 mol / L. The solution was allowed to stand for 1 hour to allow the collagen to precipitate using the salting-out effect. The precipitate was collected by centrifugation at 8000 rpm for 20 minutes and reconstituted with 0.5 mol / L hydrochloric acid solution. Dialysis (dialysis bag molecular weight cutoff of 10 kDa) was performed for 72 hours, during which time the deionized water was changed three times daily to remove sodium chloride, acid, and small molecule impurities. After dialysis, a collagen solution was obtained. The collagen content was determined according to Method VI of the Protein Content Determination Method in Chinese Pharmacopoeia 0731. The results were 8 mg / ml to 25 mg / ml. Based on the test results, purified water was added in proportion to prepare collagen solutions of the required concentration. The pH value was then adjusted by adding 0.1M hydrochloric acid solution or 0.1M sodium hydroxide solution. Type I collagen solutions of 0.5wt% (pH=5), 1.2wt% (pH=5), 2.0wt% (pH=4), 2.0wt% (pH=5), and 2.0wt% (pH=6) were prepared and refrigerated for later use in the preparation of subsequent examples and comparative examples.

[0032] Example 1 This embodiment provides a calcium sulfate-based biomimetic bone repair material and its preparation method, including the following steps: S1. Add 60g of calcium sulfate dihydrate with a particle size ≤10μm and 20g of α-tricalcium phosphate ceramic particles with a particle size of 0.25~1.0mm to 1kg of 2.0wt% (pH=5) type I collagen solution with telopeptide removal (the amount of calcium sulfate dihydrate mixture added is 8wt% of the collagen solution mass; calcium sulfate dihydrate accounts for 75wt% of the total mass of the calcium sulfate dihydrate mixture), stir and mix at 25℃ for 30min to obtain a mixture; S2. Filter the mixture under -0.09MPa for 3 minutes to concentrate the material and obtain bone paste. Place it in a mold to form it and dry it at 40℃ for 24 hours to obtain pre-formed bone blocks. S3. Vacuum dry the bone blocks at 120℃ for 20 hours; S4. After rehydrating the bone block, cure it at 40℃ and 95% humidity for 24 hours to obtain bone repair material. S5. Pack the bone repair material in a paper-plastic bag and seal it at 160℃. Sterilize it with ethylene oxide. The sterilization parameters for ethylene oxide are: temperature 38℃, humidity 60%, ethylene oxide concentration 700 mg / L, and exposure time 5h, to obtain calcium sulfate-based biomimetic bone repair material.

[0033] Performance testing: The finished product prepared in Example 1 was tested for its mechanical properties using a universal testing machine. The test results were: compressive strength 18.6±1.2MPa, flexural strength 6.8±0.5MPa.

[0034] Example 2 This embodiment provides a calcium sulfate-based biomimetic bone repair material and its preparation method, including the following steps: S1. Add 68g of calcium sulfate dihydrate with a particle size ≤10μm and 20g of β-tricalcium phosphate ceramic particles with a particle size of 0.25~1.0mm to 1kg of 2.0wt% (pH=4) type I collagen solution with telopeptides removed. (The amount of calcium sulfate dihydrate mixture added is 8.8wt% of the collagen solution mass; calcium sulfate dihydrate accounts for 77wt% of the total mass of the calcium sulfate dihydrate mixture.) Stir and mix at 25℃ for 40min to obtain a mixture. S2. Filter the mixture under -0.09MPa for 3 minutes to concentrate the material and obtain bone paste. Place it in a mold to form it and dry it at 40℃ for 24 hours to obtain pre-formed bone blocks. S3. Vacuum dry the bone blocks at 120℃ for 20 hours; S4. After rehydrating the bone block, cure it at 40℃ and 95% humidity for 24 hours to obtain bone repair material. S5. Pack the bone repair material in a paper-plastic bag and seal it at 160℃. Sterilize it with ethylene oxide. The sterilization parameters for ethylene oxide are: temperature 38℃, humidity 60%, ethylene oxide concentration 700mg / L, and exposure time 5h, to obtain calcium sulfate-based biomimetic bone repair material.

[0035] Performance testing: The finished product prepared in Example 2 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 22.3±1.5MPa, flexural strength 8.2±0.6MPa.

[0036] Example 3 This embodiment provides a calcium sulfate-based biomimetic bone repair material and its preparation method, including the following steps: S1. Add 50g of calcium sulfate dihydrate with a particle size ≤10μm and 15g of hydroxyapatite ceramic particles with a particle size of 0.25~1.0mm to 1kg of 2.0wt% (pH=6) type I collagen solution with determinated peptides (the amount of calcium sulfate dihydrate mixture added is 6.5wt% of the collagen solution mass; calcium sulfate dihydrate accounts for 77wt% of the total mass of the calcium sulfate dihydrate mixture), stir and mix at 25℃ for 40min to obtain a mixture; S2. Filter the mixture under -0.09MPa for 3 minutes to concentrate the material and obtain bone paste. Place it in a mold to form it and dry it at 40℃ for 24 hours to obtain pre-formed bone blocks. S3. Vacuum dry the bone blocks at 120℃ for 20 hours; S4. After rehydrating the bone block, cure it at 40℃ and 95% humidity for 24 hours to obtain bone repair material. S5. Pack the bone repair material in a paper-plastic bag and seal it at 160℃. Sterilize it with ethylene oxide. The sterilization parameters for ethylene oxide are: temperature 38℃, humidity 60%, ethylene oxide concentration 700 mg / L, and exposure time 5h, to obtain calcium sulfate-based biomimetic bone repair material.

[0037] Performance testing: The finished product prepared in Example 3 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 20.1±1.3MPa, flexural strength 7.5±0.4MPa.

[0038] Example 4 This embodiment provides a calcium sulfate-based biomimetic bone repair material and its preparation method, including the following steps: S1. Add 80g of calcium sulfate dihydrate with a particle size ≤10μm and 20g of bioglass (45S5 bioglass) ceramic particles with a particle size of 0.25~1.0mm to 1kg of 2.0wt% (pH=5) type I collagen solution with telopeptide removal. (The amount of calcium sulfate dihydrate mixture added is 10wt% of the collagen solution mass; calcium sulfate dihydrate accounts for 80wt% of the total mass of the calcium sulfate dihydrate mixture.) Stir and mix at 25℃ for 60min to obtain a mixture. S2. Filter the mixture under -0.1MPa for 2 minutes to concentrate the material and obtain bone paste. Place it in a mold to form it and dry it at 45℃ for 10 hours to obtain pre-formed bone blocks. S3. Vacuum dry the bone blocks at 120℃ for 20 hours; S4. After rehydrating the bone blocks, cure them at 30°C and 95% humidity for 40 hours to obtain bone repair material. S5. Pack the bone repair material in a paper-plastic bag and seal it at 160℃. Sterilize it with ethylene oxide. The sterilization parameters for ethylene oxide are: temperature 38℃, humidity 60%, ethylene oxide concentration 700mg / L, and exposure time 5h, to obtain calcium sulfate-based biomimetic bone repair material.

[0039] Performance testing: The mechanical properties of the finished product prepared in Example 4 were tested using a universal testing machine. The results were: compressive strength 25.7±1.8MPa, flexural strength 9.6±0.7MPa.

[0040] Example 5 This embodiment provides a calcium sulfate-based biomimetic bone repair material and its preparation method, including the following steps: S1. Add 18g of calcium sulfate dihydrate with a particle size ≤10μm and 12g of hydroxyapatite ceramic particles with a particle size of 0.25~1.0mm to 1kg of 0.5wt% (pH=5) type I collagen solution with determinated telopeptides (the amount of calcium sulfate dihydrate mixture added is 3wt% of the collagen solution mass; calcium sulfate dihydrate accounts for 60wt% of the total mass of the calcium sulfate dihydrate mixture), stir and mix at 35℃ for 20min to obtain a mixture; S2. Filter the mixture under -0.08MPa for 5 minutes to concentrate the material and obtain bone paste. Place it in a mold to form it. After forming, dry it at 30℃ for 40 hours to obtain pre-formed bone blocks. S3. Vacuum dry the bone blocks at 130℃ for 10 hours; S4. After rehydrating the bone block, cure it at 45℃ and 90% humidity for 10 hours to obtain bone repair material. S5. Pack the bone repair material in a paper-plastic bag and seal it at 160℃. Sterilize it with ethylene oxide. The sterilization parameters for ethylene oxide are: temperature 38℃, humidity 60%, ethylene oxide concentration 700mg / L, and exposure time 5h, to obtain calcium sulfate-based biomimetic bone repair material.

[0041] Performance testing: The finished product prepared in Example 5 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 8.2±0.6MPa, flexural strength 3.8±0.2MPa.

[0042] Comparative Example 1 This comparative example provides a traditional calcium sulfate-based bone repair material and its preparation method, including the following steps: S1. Take 60g of calcium sulfate dihydrate powder (particle size ≤10μm) and vacuum dry it at 120℃ for 20 hours to obtain calcium sulfate hemihydrate powder. S2. Mix and stir 50g of 1.2wt% type I collagen solution (pH=5) to obtain a mixed slurry (high viscosity, cannot be filtered). S3. Pour the mixed slurry directly into the mold to form it, and cure it for 24 hours at a temperature of 40℃ and a relative humidity of 95% to obtain the bone repair material. S4. After packaging, the product is sterilized with ethylene oxide. The packaging and sterilization parameters are the same as in Example 1.

[0043] Performance testing: The finished product prepared in Comparative Example 1 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 13.6±1.9MPa, flexural strength 5.2±0.7MPa.

[0044] Comparative Example 2 The difference between this comparative example and Example 1 is that the amount of calcium sulfate dihydrate mixture added is 2wt% of the collagen solution mass, that is, in step S1, 15g of calcium sulfate dihydrate with a particle size ≤10μm and 5g of α-tricalcium phosphate ceramic particles with a particle size of 0.25~1.0mm are added to 1kg of 2.0wt% (pH=5) type I collagen solution with telopeptide removal; the rest are consistent with Example 1.

[0045] Performance testing: The finished product prepared in Comparative Example 2 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 2.1±0.3MPa, flexural strength 1.2±0.1MPa.

[0046] Comparative Example 3 The difference between this comparative example and Example 1 is that the amount of calcium sulfate dihydrate mixture added is 12 wt% of the collagen solution mass, that is, in step S1, 90 g of calcium sulfate dihydrate with a particle size ≤10 μm and 30 g of α-tricalcium phosphate ceramic particles with a particle size of 0.25~1.0 mm are added to 1 kg of 2.0 wt% (pH=5) type I collagen solution with telopeptide removal. The remaining steps are the same as in Example 1.

[0047] Performance testing: The finished product prepared in Comparative Example 3 was tested for its mechanical properties using a universal testing machine. The results were: compressive strength 27.6±1.8 MPa, flexural strength 10.3±0.5 MPa. Although increasing the amount of calcium sulfate dihydrate mixture can improve its mechanical properties, it also increases brittleness, making it more prone to breakage after implantation. Considering its impact on bioactivity and osteogenic capacity, the addition amount is generally controlled within 10 wt%.

[0048] Comparative Example 4 The difference between this comparative example and Example 1 is that: in step S2, filtration is not performed, but the mixture is directly poured into the mold (because it is not filtered, the mixture has a high water content, making it difficult to solidify and obtain bone blocks).

[0049] Comparative Example 5 The difference between this comparative example and Example 1 is that vacuum heating is not performed in step S3; instead, the pre-formed bone block is directly rehydrated and cured at a relative humidity of 95%. In the resulting material, collagen did not undergo cross-linking, and calcium sulfate dihydrate was not converted to calcium sulfate hemihydrate, thus preventing curing.

[0050] Figure 1 The image shows the appearance of the bone repair material described in Embodiment 1 of the present invention. As can be seen from the image, the prepared material is relatively dense and has a small number of pores on the surface.

[0051] Figure 2 The XRD curve of the bone repair material described in Example 1 of this invention shows the characteristic peaks of calcium sulfate dihydrate, calcium sulfate hemihydrate, and tricalcium α-phosphate.

[0052] Figure 3 The IR curve of the bone repair material described in Example 1 of this invention shows obvious characteristic peaks of sulfate, phosphate and collagen.

[0053] Figure 4 The images shown are HE-stained images obtained 12 weeks after the bone repair material of the rat skull was implanted in Example 1 of this invention. The experimental procedure was as follows: 8-week-old SD rats were anesthetized with isoflurane. The surgical area was routinely prepared and disinfected. The skin was incised along the midline of the skull, the soft tissue was separated, and the skull was exposed. A full-thickness bone defect was prepared in the center of the skull using a 5mm diameter trephine (without damaging the dura mater). The disinfected bone repair material to be tested was implanted into the defect area, the skin was sutured, and the surgical area was disinfected again. The section results show that osteocytes are visible in the bone lacunae, osteoblast lining is visible at the bone edges, and the surface osteogenic activity is active. The original filling area of ​​the material was gradually replaced by new bone and connective tissue. The material outline was irregular, and the material gradually degraded and was replaced by new bone. The above results show that the material is biodegradable, the degradation rate matches the bone regeneration rate well, and there is no obvious inflammation caused by material residue.

[0054] Figure 5 The images shown are HE-stained images taken 12 weeks after rat skull implantation of the bone repair material described in Comparative Example 1 of this invention. The section results show that the bone defect was not completely healed, and the material's osteogenic capacity was only average.

[0055] The calcium sulfate-based biomimetic bone repair material of this invention exhibits excellent biocompatibility and osteogenic properties. Thanks to the optimal component ratio and manufacturing process, collagen promotes cell adhesion and growth, calcium sulfate accelerates its replacement by bone tissue, and in the later stages of bone grafting, phosphate, hydroxyapatite, and other materials continue to act as a scaffold to guide bone tissue regeneration. All components work synergistically to jointly promote bone growth.

[0056] The embodiments described above are some, but not all, of the embodiments of the present invention; the detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention; all other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. A method for preparing a calcium sulfate-based biomimetic bone repair material, characterized in that, Includes the following steps: S1. Add the calcium sulfate dihydrate mixture to the collagen solution and stir to mix to obtain a mixture; S2. Filter the mixture to obtain bone paste, place the bone paste in a mold to form it, and dry it to obtain pre-formed bone blocks; S3. The pre-formed bone block is heated under vacuum conditions to obtain a dehydrated bone block; S4. Rehydrate the dehydrated bone block and solidify it under conditions of relative humidity ≥90% to obtain bone repair material; The calcium sulfate dihydrate mixture comprises calcium sulfate dihydrate and inorganic particles, wherein the inorganic particles comprise at least one of α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, or bioglass.

2. The preparation method according to claim 1, characterized in that, In step S1, the amount of calcium sulfate dihydrate mixture added is 3 to 10 wt% of the collagen solution; the concentration of the collagen solution is 0.5 to 2.0 wt%.

3. The preparation method according to claim 1, characterized in that, In the calcium sulfate dihydrate mixture in step S1, the calcium sulfate dihydrate accounts for 60-80 wt% of the total mass of the calcium sulfate dihydrate mixture.

4. The preparation method according to claim 1, characterized in that, In step S1, the stirring and mixing is carried out at 25~35℃ for 20~60 minutes.

5. The preparation method according to claim 1, characterized in that, In step S2, the drying temperature is 30~45℃ and the time is 10~40h.

6. The preparation method according to claim 1, characterized in that, In step S3, the heating temperature under vacuum conditions is 120~130℃, and the time is 10~20h.

7. The preparation method according to claim 1, characterized in that, In step S4, the curing temperature is 30~45℃ and the time is 10~40h.

8. The preparation method according to claim 1, characterized in that, The calcium sulfate dihydrate is a powder with a particle size ≤10μm; the inorganic particles are ceramic particles with a particle size of 0.25~1.0mm; the collagen solution includes a type I collagen solution with telopeptides removed, and its pH value is 4~6.

9. A calcium sulfate-based biomimetic bone repair material obtained by the preparation method according to any one of claims 1 to 8.

10. The application of a calcium sulfate-based biomimetic bone repair material as described in claim 9 in the field of biomedical materials.

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