A bone cement solid phase composition, a method for the preparation thereof and a bone cement

Abstract

The application relates to the technical field of medical materials, in particular to a bone adhesive solid-phase composition, a preparation method thereof and a bone adhesive. The bone adhesive solid-phase composition comprises the following components in percentage by mass: 1-20% of calcium-phosphorus biological ceramics, 30-50% of phosphoserine substances, 0.1-8% of absorbable hemostatic materials and 100% of tetracalcium phosphate; the calcium-phosphorus biological ceramics are weakly alkaline calcium-phosphorus biological ceramics, and the pH value of a 100g / L aqueous solution of the calcium-phosphorus biological ceramics is 7-10. The application can reduce the intensity of initial reaction between alkaline substances and phosphoserine substances, prolong the continuous reaction time, and thus reduce the reaction temperature.

Description

Technical Field

[0001] This application relates to the field of medical materials technology, specifically to a bone adhesive solid composition, its preparation method, and the bone adhesive itself. Background Technology

[0002] Bone adhesives are common medical consumables used in orthopedic surgery to adhere bone to promote repair. Existing bone adhesives often consist of tetracalcium phosphate, phosphoserine, and other additives. For example, CN117338992A, entitled "A Bone Adhesive and its Preparation Method," discloses a bone adhesive whose raw materials include tetracalcium phosphate, phosphoserine-like substances (e.g., phosphoserine), sustained-release microspheres, and a liquid phase component. The mass ratio of tetracalcium phosphate to phosphoserine-like substances is 3:(1-2). The tetracalcium phosphate content is higher than the phosphoserine-like substance content, which increases the strength of the bone adhesive.

[0003] However, the reaction between tetracalcium phosphate and phosphoserine is an acid-base reaction. Phosphoserine has a pH < 3, while tetracalcium phosphate has a pH > 13. The reaction temperature is high within minutes, and the larger the volume of the bone binder, the higher the reaction temperature, sometimes even approaching 80°C, far exceeding the tolerance temperature of bone tissue in the body. Bone morphogenetic protein (BMP), which promotes bone tissue formation, is often added to bone binder formulations. The short-term storage temperature for BMP is below 10°C, and the operating temperature is ≤ 37°C. Excessively high storage and operating temperatures will cause BMP inactivation. Summary of the Invention

[0004] In view of this, the present invention provides a solid-phase composition of bone adhesive, a method for preparing the same, and a bone adhesive. This solid-phase composition of bone adhesive can reduce the intensity of the initial reaction between alkaline substances and phosphoserine-like substances, prolonging the reaction time and thus achieving the purpose of lowering the reaction temperature.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides a bone adhesive solid phase composition, which, by weight percentage, comprises the following components:

[0007]

[0008] Calcium-phosphorus bioceramics are weakly alkaline, and the pH value of a 100g / L aqueous solution of calcium-phosphorus bioceramics is 7-10.

[0009] Preferably, the pH value of a 100 g / L aqueous solution of calcium-phosphorus bioceramics is 7 to 9.

[0010] For example, the mass percentage of calcium-phosphorus bioceramics in the bone adhesive solid composition is any value from 1%, 5%, 10%, 15%, 20%, or any value from any range of any two values.

[0011] Preferably, the calcium-phosphorus bioceramic content in the bone binder solid composition is 5% to 15% by mass.

[0012] For example, the mass percentage of phosphoserine in the bone adhesive solid composition is any one of 30%, 35%, 40%, 45%, or 50%, or any one of any two values ​​within a range.

[0013] For example, the mass percentage of absorbable hemostatic material in the bone adhesive solid composition is any one of 0.1%, 1%, 2%, 4%, 8%, or any one of any two values ​​within a range.

[0014] Preferably, the absorbable hemostatic material in the bone adhesive solid phase composition comprises 2% to 8% by mass.

[0015] In embodiments of the present invention, calcium-phosphorus bioceramics include at least one of β-tricalcium phosphate, bioactive glass, and hydroxyapatite.

[0016] In embodiments of the present invention, phosphoserine-like substances include at least one of phosphoserine, polyphosphoserine, and phosphorylated polypeptides.

[0017] In a specific embodiment of the present invention, the phosphoserine-like substance is phosphoserine.

[0018] In this invention, the larger the particle size of the phosphoserine-like substances, the slower the reaction with tetracalcium phosphate and calcium phosphate bioceramics. Preferably, the particle size of the phosphoserine-like substances is 30–100 μm. Exemplarily, the particle size of the phosphoserine-like substances is any value from 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, and 100 μm, or any value within a range of any two values.

[0019] Preferably, the particle size of phosphoserine derivatives is 40–80 μm.

[0020] Preferably, the absorbable hemostatic material includes absorbable filaments and absorbable hemostatic particles adhered to the surface of the absorbable filaments.

[0021] Preferably, the mass ratio of absorbable hemostatic granules to absorbable sutures is (1-5):1. For example, the mass ratio of absorbable hemostatic granules to absorbable sutures is any value from 1:1, 2:1, 3:1, 4:1, 5:1 or any value from any range of any two values.

[0022] In this embodiment of the invention, the raw materials for preparing absorbable hemostatic granules include at least one of starch, gelatin, sodium hyaluronate, collagen, chitosan, silk protein, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, polyamide, tannic acid, sorbitol, and polyethylene glycol.

[0023] In a specific embodiment of the present invention, starch is used as the raw material for preparing absorbable hemostatic granules. Other types of raw materials for preparing absorbable hemostatic granules can also achieve the present invention.

[0024] Preferably, the absorbable hemostatic particles have a particle size of 10–100 μm. For example, the particle size of the absorbable hemostatic particles can be any value from 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, and 100 μm, or any value within a range of any two values.

[0025] Preferably, the absorbable hemostatic particles have a particle size of 30–70 μm.

[0026] In embodiments of the present invention, the raw materials for preparing absorbable yarns include at least one of polyglycolic acid (PGA), polylactic acid, polylactic acid-glycolic acid copolymer (PLGA), and collagen.

[0027] In a specific embodiment of the present invention, the raw material for preparing absorbable yarn includes polyglycolic acid. Other types of raw materials for preparing absorbable yarn can also achieve the present invention.

[0028] Preferably, the absorbable yarn has a diameter of 5–50 μm and a length of 0.5–20 mm.

[0029] Preferably, the absorbable yarn has a diameter of 10–20 μm and a length of 1–10 mm.

[0030] In embodiments of the present invention, the absorbable yarn can be either pretreated or untreated, both methods achieving the objective of the present invention. The pretreatment step for the absorbable yarn includes treating the surface of the absorbable yarn with a lubricant and / or a plasticizer. For example, the lubricant includes calcium stearate, and the plasticizer includes polycaprolactone.

[0031] In a second aspect, the present invention provides a method for preparing the above-mentioned bone adhesive solid composition, comprising the following steps:

[0032] S1, the raw materials for preparing absorbable yarn are spun to obtain absorbable yarn; absorbable hemostatic particles are adhered to the surface of absorbable yarn; the absorbable yarn with the adhered absorbable hemostatic particles is cut to obtain absorbable hemostatic material.

[0033] S2, calcium-phosphorus bioceramics, phosphoserine-like substances, absorbable hemostatic materials, and tetracalcium phosphate are mixed to obtain a bone adhesive solid phase composition.

[0034] In an embodiment of the present invention, during the preparation of absorbable hemostatic material, absorbable hemostatic particles are sprayed onto the filament outlet or placed in the area where the filament passes before cooling down, so that the absorbable filament surface is uniformly adhered to the absorbable hemostatic particles. After cooling and drying, a beaded material is obtained, which is then cut into fiber segments.

[0035] In this embodiment of the invention, conventional spinning technology is used. This invention is not limited thereto.

[0036] Thirdly, the present invention provides a bone adhesive comprising the above-described solid phase composition and liquid phase of the bone adhesive.

[0037] Preferably, the liquid phase includes at least one of purified water, artificial saliva, simulated body fluid, cell preservation solution, water for injection, physiological saline, distilled water, platelet-rich plasma, soluble phosphate solution, and physiological saline containing 0.1% to 30% of the drug.

[0038] In embodiments of the present invention, the bone adhesive further includes osteogenic active ingredients for promoting the repair of fractures or bone injuries.

[0039] In embodiments of the present invention, the osteogenic active ingredient includes at least one of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP).

[0040] Preferably, the mass ratio of the bone adhesive solid phase composition, the osteogenic active ingredient, and the liquid phase is 1:(0-0.1):(0.15-0.35).

[0041] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0042] 1. This invention incorporates a weakly alkaline calcium-phosphorus bioceramic into the solid phase composition of a bone binder. Compared to tetracalcium phosphate, calcium-phosphorus bioceramic has a lower pH value and is weakly alkaline. This invention combines two alkaline substances, strongly alkaline tetracalcium phosphate and weakly alkaline calcium-phosphorus bioceramic, which can reduce the intensity of the initial reaction between the alkaline substances and phosphoserine-like substances, prolonging the reaction time and thus lowering the reaction temperature. This allows for the maintenance of the activity of osteogenic active ingredients such as bone morphogenetic protein (BMP) when added subsequently, preventing deactivation.

[0043] 2. The liquid phase component in existing bone adhesives can ensure that the bone adhesive has flow properties during the operation time. However, when conducting live animal tests, the bone adhesive needs to wait about 10 minutes to cure. During the waiting period, the bone adhesive will dry out and needs to be continuously moistened with physiological saline. However, the blood, tissue fluid and external liquids that seep from the live animal test site can only wet the surface of the adhesive, while the inside is still dry and cracked, which is not conducive to the curing of the bone adhesive.

[0044] The absorbable hemostatic material of this invention includes absorbable threads and absorbable hemostatic particles adhered to the surface of the absorbable threads. The absorbable hemostatic particles have a strong liquid absorption capacity, which stops bleeding and absorbs liquid. They are mixed inside the adhesive and continuously provide a moist environment inside the adhesive to ensure that the internal reaction continues.

[0045] 3. Existing bone adhesives form a dense bond through solid-liquid bonding. However, during in vivo degradation, they only degrade gradually from the outside in, failing to form a continuous spatial connection. This hinders blood flow, and the internal structure does not degrade immediately. If more absorbable hemostatic particles are added, the particles will come into contact with each other, allowing the bone adhesive to absorb liquid through a continuous flow, thus reducing its strength. If fewer absorbable hemostatic particles are added, the bone adhesive strength will be improved, but the particles will be encapsulated by the adhesive, creating numerous isolated islands of absorbable particles, still making it difficult to form a continuous connection.

[0046] The absorbable hemostatic material of this invention combines absorbable threads and absorbable hemostatic particles, ensuring spatial connectivity. This prevents the formation of excessive isolated hemostatic particle islands, while the absorbable threads also enhance the mechanical properties of the bone adhesive. Simultaneously, the absorbable hemostatic material is irregularly distributed within the bone adhesive. The absorbable hemostatic particles degrade relatively quickly, approximately 3-14 days, while the absorbable threads degrade over a period of 7-60 days, continuously increasing the toughness and shear strength of the bone adhesive. After the absorbable hemostatic material degrades, it forms a porous structure with spatial connectivity throughout the bone adhesive, providing space for the growth of blood vessels and osteoblasts without hindering blood supply. Detailed Implementation

[0047] This invention discloses a bone adhesive solid composition, its preparation method, and the bone adhesive itself. Those skilled in the art can refer to this document and appropriately modify the process parameters to achieve the desired result. It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0048] In the description of this invention, the list of items connected by the term "at least one of" or other similar terms may mean any combination of the listed items. For example, if items A and B are listed, then the phrase "at least one of A and B" means only A; only B; or A and B. In another example, if items A, B, and C are listed, then the phrase "at least one of A, B, and C" means only A; or only B; only C; A and B (excluding C); A and C (excluding B); B and C (excluding A); or all of A, B, and C. Item A may contain a single element or multiple elements. Item B may contain a single element or multiple elements. Item C may contain a single element or multiple elements.

[0049] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges or individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0050] Unless otherwise specified, all embodiments and optional embodiments of this application can be combined to form new technical solutions.

[0051] Unless otherwise specified, all technical features and optional technical features of this application may be combined to form new technical solutions.

[0052] Unless otherwise specified, the terms "comprising" and "including" as used in this application can be open-ended or closed-ended. For example, "comprising" and "including" can mean that other components not listed may also be included, or that only the listed components may be included.

[0053] The reagents, instruments, and materials used in this invention can all be obtained through commercial channels.

[0054] The present invention will be further illustrated below with reference to the embodiments:

[0055] Example 1

[0056] 1. Composition of the bone adhesive solid phase composition (by mass percentage)

[0057]

[0058] 2. Preparation method of bone adhesive solid composition

[0059] Step (1): The raw material for preparing absorbable yarn (polyglycolic acid PGA) is spun into yarn with a diameter of 14 μm; absorbable hemostatic granules (starch granules with a particle size of 50 μm) are sprayed onto the yarn outlet so that the absorbable yarn surface is uniformly adhered to the absorbable hemostatic granules, and the mass ratio of absorbable hemostatic granules to absorbable yarn is 3:1; after cooling and drying, a beaded material is obtained, which is then cut into fiber segments with a length of 10 mm to obtain absorbable hemostatic material.

[0060] Step (2) involves mixing calcium-phosphorus bioceramics, phosphoserine-like substances, absorbable hemostatic materials, and tetracalcium phosphate to obtain a bone adhesive solid phase composition.

[0061] Example 2 group

[0062] The only difference between this embodiment and Embodiment 1 is that the amounts of calcium-phosphorus bioceramics and tetracalcium phosphate are different, resulting in a total proportion of calcium-phosphorus bioceramics and tetracalcium phosphate of 56%.

[0063] Example 2a: The content of calcium-phosphorus bioceramics is 1%;

[0064] Example 2b: The content of calcium-phosphorus bioceramics is 5%;

[0065] Example 2c: The content of calcium-phosphorus bioceramics is 15%;

[0066] Example 2d: The content of calcium-phosphorus bioceramics is 20%.

[0067] Example 3 Group

[0068] The only difference between this embodiment and Embodiment 1 is that the amount of absorbable hemostatic material and tetracalcium phosphate used is different, so that the total proportion of absorbable hemostatic material and tetracalcium phosphate used is 50%.

[0069] Example 3a: The content of absorbable hemostatic material is 0.1%;

[0070] Example 3b: The content of absorbable hemostatic material is 1%;

[0071] Example 3c: The content of absorbable hemostatic material is 2%;

[0072] Example 3d: The content of absorbable hemostatic material is 8%.

[0073] Example 4 group

[0074] The only difference between this embodiment and Embodiment 1 is that the types of calcium-phosphorus bioceramics are different.

[0075] Example 4a: Bioactive glass (pH approximately 9.0);

[0076] Example 4b: Hydroxyapatite (pH approximately 7.5).

[0077] Example 5 group

[0078] The only difference between this embodiment and Embodiment 1 is that the mass ratio of absorbable hemostatic granules to absorbable sutures is different.

[0079] Example 5a: The mass ratio of absorbable hemostatic granules to absorbable sutures is 1:1;

[0080] Example 5b: The mass ratio of absorbable hemostatic granules to absorbable sutures is 5:1.

[0081] Comparative Example 1

[0082] The only difference between this comparative example and Example 1 is that the content of calcium-phosphorus bioceramics is 0%, and the amount of tetracalcium phosphate is 56%.

[0083] Comparative Example 2

[0084] The only difference between this comparative example and Example 1 is that the content of absorbable hemostatic material is 0%, and the amount of tetracalcium phosphate is 50%.

[0085] Comparative Example 3

[0086] The only difference between this comparative example and Example 1 is that the absorbable threads and absorbable hemostatic particles in the absorbable hemostatic material are not bonded together and are in a separate state.

[0087] Test case

[0088] 1. Maximum temperature test

[0089] 5g of the bone binder solid composition was kept at (23±1)℃ and humidity not less than 40% for at least 2 hours, and then the test was carried out under (23±1)℃ and humidity not less than 40%. Ambient temperature was recorded using thermocouples. The bone binder solid composition powder was mixed with purified liquid water at a mass ratio of 1:0.25 and stirred uniformly. The mixture was then injected into a 76mm diameter, 30mm high PTFE female mold. A male mold matching the inner diameter was used and fixed to ensure a constant volume of bone binder in the mold. A reinforcing polymer plate could be used along the bottom of the mold to prevent warping during the bone binder reaction, removing any bone binder extruded from the mold. Temperature was continuously measured until shortly after the temperature began to drop. Each sample was tested 3 times.

[0090] Table 1

[0091]

[0092] As shown in Table 1, compared with Comparative Example 1, Examples 1-5 all reduced the reaction temperature. Specifically, the amount of calcium-phosphorus bioceramics used in Examples 2a, 2b, 1, 2c, and 2d gradually increased; the more calcium-phosphorus bioceramics added, the lower the reaction temperature. However, when the amount added exceeded 10%, the temperature reduction decreased, and the test temperature remained above 40°C.

[0093] In contrast, Comparative Example 1, which did not contain calcium-phosphorus bioceramics, had a reaction temperature as high as 78°C.

[0094] 2. Liquid Absorption Capacity Test

[0095] In an indoor environment of (23±1)℃ and humidity not less than 40%, 2 mL of rabbit venous blood was drawn according to the solid-liquid mass / volume ratio of bone binder solid composition to rabbit venous blood of 1 g: 0.21 mL. The blood was then used to prepare red blood cell plasma through a blood separation device. 0.25 mL of plasma was squeezed onto a glass slide. The mixed bone binder (bone binder solid composition powder and purified water mixed at a mass ratio of 1:0.25) was squeezed onto the glass containing plasma. Another glass cover was placed on the bone binder, and the material was squeezed by hand with a shearing motion to form a film. The adhesion of the bone binder film to the glass was then observed.

[0096] The bone adhesive was prepared into rods with a diameter of 6 mm and a length of 12 mm, placed in PBS buffer, and incubated in a shaker at (37±1)℃ in the room. After 90 days of degradation, the internal porosity was tested.

[0097] Weigh 1.0g of the bone binder solid composition. Pour the prepared bone binder (bone binder solid composition powder and purified water mixed at a mass ratio of 1:0.25) into a stainless steel cylindrical mold (12mm high and 6mm in diameter). Demold immediately. Immerse the bone binder sample in a beaker containing simulated body fluid (SBF solution). Place it in a constant temperature shaker and shake for 15 minutes. Remove the solidified body, dry it, and weigh the total sample mass and the mass of the collapsed sample. Collapsed sample mass / total sample mass = collapse rate.

[0098] The bone binder solid composition powder was mixed with purified water at a mass ratio of 1:0.25 until homogeneous. The mixture was then applied to a stainless steel mold with a diameter of 6 mm and a height of 18 mm using a stainless steel scraper. The mixture was molded under pressure and cured for 10 minutes before demolding. The sample was then cured in a constant temperature and humidity chamber at 37°C and 98% humidity for 3 days, followed by drying in a 37°C oven. Both ends of the sample were ground smooth, ensuring a cylindrical height of 12 mm. The compressive strength was determined according to ISO 9917-1 standard using a universal testing machine in constant loading rate mode at a loading rate of 1 mm / min.

[0099] Table 2

[0100]

[0101] As shown in Table 2, compared with Comparative Example 2, Examples 1-5 all increased porosity, and except for Example 2d, Examples 1-5 all decreased the collapse rate, indicating that Examples 1-5 all have strong liquid absorption capacity. Specifically, the amount of absorbable hemostatic material in Examples 3a, 3b, 3c, 1, and 3d gradually increased. The more absorbable hemostatic material added, the stronger the liquid absorption capacity and the greater the probability of forming pores in the hemostatic particles. After absorbing liquid, the hemostatic particles can increase the internal wetted volume ratio of the bone adhesive. In contrast, no absorbable hemostatic material was added in Comparative Example 2. Within 45 seconds, the adhesive had already undergone an adhesive reaction, and the bone adhesive in Comparative Example 2 could not absorb excess tissue fluid and blood, resulting in reduced adhesive efficiency.

[0102] Tetracalcium phosphate and absorbable hemostatic materials together affect the curing strength and collapse of the product. In Example 2d, there was more β-tricalcium phosphate and less tetracalcium phosphate, resulting in lower strength and higher collapse rate.

[0103] Regarding compressive strength, in Examples 3a, 3b, 3c, 1, and 3d, the compressive strength initially decreased and then increased as the amount of absorbable hemostatic material gradually increased. However, the compressive strength of Example 3d with 8% addition was still lower than that of Comparative Example 2 with 0% addition. This may be because the increased amount of absorbable hemostatic particles weakens the bonding of the bone adhesive structure, thus reducing interfacial strength.

[0104] In Comparative Example 3, although the liquid absorption capacity was similar to that of Example 1, the absorbable filaments and absorbable hemostatic particles did not stick together, the degree to which body fluids and enzymes entered the interior was reduced, and the degradation rate was slower.

[0105] Clinical application examples

[0106] Materials were prepared according to a mass ratio of bone binder solid phase composition powder, bone morphogenetic protein (BMP), and purified water of 1:0.005:0.25. Then, BMP and purified water were first mixed thoroughly, and the resulting BMP solution was then mixed thoroughly with any one of the bone binder solid phase composition powders from Examples 1-5 to obtain a bone binder for the treatment of fractures or bone defects.

[0107] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A bone cement solid phase composition characterized in that, The bone adhesive solid composition comprises the following components by weight percentage: Calcium-phosphorus bioceramics 1%~20%, phosphoseserine substances 30%~50%, absorbable hemostatic materials 0.1%~8%, and tetracalcium phosphate supplemented to 100%; The calcium-phosphorus bioceramic is a weakly alkaline calcium-phosphorus bioceramic, and the pH value of a 100g / L aqueous solution of the calcium-phosphorus bioceramic is 7~10. The calcium-phosphorus bioceramics include at least one of β-tricalcium phosphate, bioactive glass, and hydroxyapatite; The phosphoserine-like substances include at least one of phosphoserine, polyphosphoserine, and phosphorylated peptides; The absorbable hemostatic material includes absorbable threads and absorbable hemostatic particles adhered to the surface of the absorbable threads. The method for preparing the absorbable hemostatic material includes: spinning the raw material for preparing absorbable yarn to obtain absorbable yarn; then spraying the absorbable hemostatic particles onto the yarn outlet, so that the surface of the absorbable yarn is uniformly adhered to the absorbable hemostatic particles; after cooling and drying, a beaded material is obtained, which is then cut into fiber segments with a length of 10 mm to obtain the absorbable hemostatic material; wherein, the mass ratio of the absorbable hemostatic particles to the absorbable yarn is 1~5:

1. The raw materials for preparing the absorbable hemostatic granules include at least one of starch, gelatin, sodium hyaluronate, collagen, chitosan, silk protein, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, polyamide, tannic acid, sorbitol, and polyethylene glycol; the particle size of the absorbable hemostatic granules is 10~100μm. The raw materials for preparing the absorbable yarn include at least one of polyglycolic acid (PGA), polylactic acid, polylactic acid-glycolic acid copolymer (PLGA), and collagen; the absorbable yarn has a diameter of 5~50μm and a length of 10~20mm.

2. A method for preparing the bone adhesive solid composition according to claim 1, characterized in that, Includes the following steps: S1, the raw materials for preparing absorbable yarn are spun to obtain absorbable yarn; then the absorbable hemostatic particles are sprayed onto the yarn outlet, so that the surface of the absorbable yarn is uniformly adhered to the absorbable hemostatic particles; after cooling and drying, a beaded material is obtained, which is then cut into fiber segments with a length of 10 mm to obtain absorbable hemostatic material; wherein, the mass ratio of the absorbable hemostatic particles to the absorbable yarn is 3:

1. S2, calcium-phosphorus bioceramics, phosphoserine-like substances, the absorbable hemostatic material, and tetracalcium phosphate are mixed to obtain a bone adhesive solid phase composition.

3. A bone adhesive, characterized in that, The bone adhesive comprises the solid phase composition and liquid phase of the bone adhesive according to claim 1; The liquid phase includes at least one of purified water, artificial saliva, simulated body fluid, cell preservation solution, physiological saline, platelet-rich plasma, soluble phosphate solution, and physiological saline containing 0.1% to 30% drug.

4. The bone adhesive according to claim 3, characterized in that, The bone adhesive further includes osteogenic active ingredients; the osteogenic active ingredients include at least one of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP).

5. The bone adhesive according to claim 4, characterized in that, The mass ratio of the bone adhesive solid phase composition, the osteogenic active ingredient, and the liquid phase is 1:(0~0.1):(0.15~0.35).

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