A bioactive bone adhesive and its preparation method and application

Abstract

This invention discloses a bioactive bone adhesive, its preparation method, and its applications. The adhesive comprises a bioactive glass component as a functional enhancement, which, through ligand-ion interactions, is composited with tetracalcium phosphate, O-phospho-L-serine, and polyacrylic acid. During the curing process, this invention effectively regulates the local acidic environment and stabilizes the system pH in a slightly alkaline range after 7 days, which is beneficial for osteoblast activity and bone tissue regeneration. After 24 hours of culture in simulated body fluid, the initial adhesion strength to titanium alloys reached 7.53 MPa; after 7 days in a humid environment, the compressive strength remained at 106.1 MPa. This invention also exhibits excellent in vitro mineralization capacity, cell compatibility, and osteogenic activity, with overall performance significantly superior to conventional bone repair materials, showing broad clinical application prospects in fracture fixation and bone defect repair.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a bioactive bone adhesive, its preparation method, and its application. Background Technology

[0002] Fracture repair, especially in cases involving comminuted fractures or infection, remains a significant clinical challenge. Traditional fixation methods (such as internal metal implants) often result in extensive surgical trauma, increased risk of infection, stress shielding effects, and the need for secondary removal surgery, imposing additional physical and financial burdens on patients. To address this issue, injectable biodegradable bone adhesives have emerged as a promising alternative, offering advantages such as mechanical fixation, minimal invasiveness, and biocompatibility. These materials are particularly suitable for bone-bone interface bonding and inducing osteogenic processes.

[0003] Early bone repair materials such as polymethyl methacrylate (PMMA) achieved initial success as bone cement. However, its non-degradability and exothermic polymerization properties can lead to local necrosis and bond failure. Although calcium phosphate bone cement is biocompatible, it is still limited by slow gelation, significant brittleness, and insufficient adhesion in moist environments. Commercially available medical adhesives, such as fibrin glue, have weak adhesion and are suitable for soft tissue bonding, but are insufficient to support the strength of bone tissue; cyanoacrylate-based adhesives have better bonding strength, but their monomers are toxic and their bonding effect on moist tissue surfaces in vivo is poor.

[0004] A polyacrylic acid (PAA) / tetracalcium phosphate (TTCP) / o-phosphoric acid-L-serine (OPLS)-reinforced bone adhesive, developed by integrating biomimetic design concepts and an organic-inorganic composite strategy, achieves enhanced bond strength, mechanical robustness, and controllable degradation. However, this system exhibits acidic degradation characteristics, leading to impaired cell compatibility and osteogenic properties. The low pH microenvironment activates osteoclasts, accelerates mineral dissolution, and inhibits osteoblast differentiation, ultimately triggering inflammatory responses and bone loss. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0006] In view of the problems existing in the above and / or prior art, the present invention is proposed.

[0007] Therefore, the purpose of this invention is to overcome the shortcomings of the prior art and provide a bioactive bone adhesive, its preparation method, and its application.

[0008] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a bioactive bone adhesive, characterized in that it comprises, Tetracalcium phosphate, The composition comprises o-phospho-L-serine, bioactive glass as a functional enhancing component, and a solution selected from aqueous polyacrylic acid solution or aqueous sodium hyaluronate solution; wherein the components are bonded to form a stable composite material through coordination bonds and ionic bonds between phosphate groups, carboxyl groups and calcium ions.

[0009] As a preferred embodiment of the bioactive bone adhesive of the present invention, the mass ratio of the total mass of the o-phospho-L-serine to tetracalcium phosphate and bioactive glass is (0.3:1) to (0.6:1).

[0010] In a preferred embodiment of the bioactive bone adhesive of the present invention, the mass ratio of tetracalcium phosphate to bioactive glass is (5.6~19):1.

[0011] As a preferred embodiment of the bioactive bone adhesive of the present invention, the mass ratio of the polyacrylic acid aqueous solution to all solid components tetracalcium phosphate, o-phospho-L-serine and bioactive glass is (0.31:1) to (0.46:1).

[0012] As a preferred embodiment of the bioactive bone adhesive of the present invention, the mass ratio of the sodium hyaluronate aqueous solution to all solid components tetracalcium phosphate, o-phospho-L-serine and bioactive glass is (0.23:1) to (0.46:1).

[0013] As a preferred embodiment of the bioactive bone adhesive of the present invention, the adhesive has an initial adhesion strength of 3.57~5.72 MPa to titanium alloy after curing at room temperature for 15 minutes; and an initial adhesion strength of 6.10~7.56 MPa to titanium alloy after culturing in simulated body fluid for 24 hours.

[0014] As a preferred embodiment of the bioactive bone adhesive of the present invention, the adhesive maintains a compressive strength of 90.29 MPa to 113.93 MPa after being placed in a humid environment for 7 days.

[0015] As a preferred embodiment of the bioactive bone adhesive of the present invention, the cell viability in the CCK8- assay at day 1 is 101.64%~119.07%, the ALP quantitative analysis result at day 7 is 0.095~0.109, and the Alizarin Red staining quantitative result at day 14 is 2.407~3.326.

[0016] Another object of the present invention is to overcome the shortcomings of the prior art and provide a bioactive bone adhesive for use in fracture fixation or bone defect repair.

[0017] Another object of the present invention is to overcome the shortcomings of the prior art and provide a bioactive bone adhesive and a medical titanium alloy implant; wherein the adhesive acts as an interface functional layer to mediate the biomechanical integration and bioactive coupling between the implant and the host bone tissue.

[0018] Beneficial effects of this invention: (1) The bone adhesive prepared by the present invention is simple to use and can be obtained by simply using a physical mixing method. It is easy to operate in clinical practice and can greatly facilitate medical staff in fixing fractures or implants.

[0019] (2) The bone adhesive prepared by the present invention can significantly improve the problem of excessive acidity in the existing material system, making it a slightly alkaline environment, which is more conducive to osteogenic formation.

[0020] (3) The bone adhesive prepared by the present invention significantly improves the bioactivity problem of existing material systems, greatly promotes cell growth and proliferation, and is beneficial to osteogenic differentiation of cells.

[0021] (4) The bone adhesive prepared by the present invention enhances the mechanical properties of existing materials, exhibits excellent adhesion and compressive shear properties, and is expected to replace internal fixation metal fixation of fractures, reducing the pain caused by secondary surgery.

[0022] (5) The bone adhesive prepared by this invention has the characteristic of synchronous fracture repair and gradual degradation. In the early stage, it can maintain stable support, and in the later stage, it can conform to bone regeneration to provide space and avoid the space-occupying effect. Attached Figure Description

[0023] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments 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. Wherein: Figure 1 The pH change of bone adhesive in PBS is shown in an embodiment of the present invention.

[0024] Figure 2 The compressive shear strength of the bone adhesive after curing on a titanium alloy surface for 15 minutes, as described in this embodiment of the invention.

[0025] Figure 3 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 and control group O30 T 100 P 60 The compressive shear strength of titanium alloy after curing on the surface for 15 min and immersion in deionized water for 24 h.

[0026] Figure 4 The tensile strength of the bone adhesive on the titanium alloy surface after curing for 15 minutes is shown in the embodiment of the present invention.

[0027] Figure 5 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 and control group O 30 T 100 P 60 Tensile strength after curing on titanium alloy surface for 15 min and immersion in deionized water for 24 h.

[0028] Figure 6 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 and control group O 30 T 100 P 60 Compressive shear strength after the bone block has solidified for 15 minutes.

[0029] Figure 7 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 and control group O 30 T 100 P 60 Tensile strength after the bone block has solidified for 15 minutes.

[0030] Figure 8 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 The compressive strength of the adhesive after 0, 1, 3, and 7 days in simulated body fluid at 37°C.

[0031] Figure 9 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 Scanning electron microscope images of the adhesive after 0, 7, and 14 days in simulated body fluid at 37°C.

[0032] Figure 10 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 XRD results of the adhesive after 0, 7 and 14 days in simulated body fluid at 37°C.

[0033] Figure 11 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 Adhesive and control group O 30 T 100 P 60 Toxicity test results of mouse embryonic osteoblast precursor cells cultured in extract for 3 days.

[0034] Figure 12 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 Results of alkaline phosphatase quantification and staining in mouse embryonic osteoblast precursor cells cultured in adhesive and control group extracts for 7 days.

[0035] Figure 13 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 Quantitative analysis and staining results of calcium matrix in mouse embryonic osteoblast precursor cells cultured in adhesive and control group extracts for 14 days.

[0036] Figure 14 Bone adhesive B5O is an embodiment of the present invention. 30 T 95 P 60 Degradation results of the adhesive after 12 weeks of isothermal shaking in 37°C SBF.

[0037] Figure 15 The compression shear test results are for the adhesives prepared with different OPLS contents according to the present invention.

[0038] Figure 16 The results of compression shear tests are for adhesives prepared with different PAA concentrations according to the present invention.

[0039] Figure 17 The results of compression shear tests are for adhesives prepared using HA with different molecular weights / concentrations / masses according to this invention. Detailed Implementation

[0040] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0041] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0042] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0043] Unless otherwise specified, all raw materials used in the embodiments of this invention are commercially available. See Table 1 for details.

[0044] Table 1

[0045] 80-150W 2% 45mg HA: 80-150W molecular weight 2% mass fraction 45mg sodium hyaluronate solution.

[0046] 80-150W 1% wt 30mg HA: 80-150W molecular weight 1% mass fraction 30mg sodium hyaluronate solution.

[0047] 80-150W 0.25% wt 30mg HA: 80-150W molecular weight 0.25% mass fraction 30mg sodium hyaluronate solution.

[0048] 80-150W 0.5% wt 30mg HA: 80-150W molecular weight 0.5% mass fraction 30mg sodium hyaluronate solution.

[0049] 80-150W 2% wt 60mg: 80-150W molecular weight 2% mass fraction 60mg sodium hyaluronate solution.

[0050] 40-80W 2.5% wt 30mg HA: 40-80W molecular weight 2.5% mass fraction 30mg sodium hyaluronate solution.

[0051] 10-20W 2.5% wt 30mg HA: 10-20W molecular weight 2.5% mass fraction 30mg sodium hyaluronate solution.

[0052] Example 1 This embodiment provides a method for preparing a bioactive bone adhesive: (1) The adhesive is weighed with 0.3% phosphoserine (O-phospho-L-serine) at a mass ratio (w / w). OPLS, tetracalcium phosphate (TTCP), and bioactive glass (BG) were mixed uniformly. 5 mg of BG was introduced as a partial substitute for TTCP, maintaining the OPLS to TTCP-BG mixture mass ratio at 0.3. Then, 25% (Mw) of an aqueous solution of polyacrylic acid (PAA) was added at a liquid-to-solid mass ratio (mg) of 0.46, and the mixture was stirred uniformly to obtain the adhesive of this invention.

[0053] (2) pH test: The adhesive was injected into the silicone mold and cured for 15 minutes. The mold was then removed to form a cylindrical sample with a diameter of 6 mm and a height of 4 mm. The sample was weighed and PBS (pH=7.3) was added to make the solid-liquid ratio 1:10. The sample was placed in a constant temperature shaker at 37℃ and the pH value was tested at 15 minutes and 1 to 7 days. The number of samples tested was 3.

[0054] Experimental results are as follows Figure 1 As shown: pH changes of the adhesive in SBF were monitored over 7 days, B5O 30 T 95 P 60 Initially, it is weakly acidic to neutral with a pH of 6.88. It gradually stabilizes in the weakly alkaline range within the third day and maintains a stable pH of 7.28 after 7 days.

[0055] Example 2 The difference from Example 1 is that the bioactive glass mass is 10 mg, otherwise it is the same as Example 1.

[0056] like Figures 1-4 As shown, the B obtained in this embodiment 10 O 30 T 90 P 60 The bone adhesive exhibited an initial adhesion strength of 4.49 MPa to titanium alloy after curing at room temperature for 15 minutes, and 6.99 MPa after 24 hours of incubation in simulated body fluid. After 7 days in a humid environment, its compressive strength remained at 96.29 MPa. The initial tensile strength to titanium alloy after curing at room temperature for 15 minutes was 3.36 MPa, and 3.12 MPa after 24 hours of incubation in simulated body fluid. Cell viability was 109.52% in a 1-day CCK8 assay and remained stable at pH 7.31 after 7 days.

[0057] Example 3 The difference from Example 1 is that the bioactive glass mass is 15 mg, otherwise it is the same as Example 1.

[0058] like Figures 1-4 As shown, the B obtained in this embodiment15 O 30 T 85 P 60 The bone adhesive exhibited an initial adhesion strength of 4.13 MPa to titanium alloy after curing at room temperature for 15 minutes, and 6.3 MPa after 24 hours of incubation in simulated body fluid. After 7 days in a humid environment, its compressive strength remained at 94.9 MPa. The initial tensile strength to titanium alloy after curing at room temperature for 15 minutes was 2.52 MPa, and 3.01 MPa after 24 hours of incubation in simulated body fluid. Cell viability was 108.8% in a 1-day CCK8 assay and remained stable at pH 7.47 after 7 days.

[0059] Comparative Example 1 The difference from Example 1 is that no bioactive glass is added; otherwise, it is the same as Example 1.

[0060] from Figure 1 It can be seen that O 30 T 100 P 60 The pH of the adhesive group varied around 6.4 over 1-7 days, while the pH of the experimental group with added BG was consistently higher than 0. 30 T 100 P 60 The environment gradually shifted from weakly acidic to weakly alkaline and remained stable. This indicates that the addition of BG effectively buffered and balanced the weakly acidic environment caused by PAA, thereby eliminating its potential adverse effects on cell activity and osteogenic processes.

[0061] Example 4 Compression shear test: Two cylindrical Ti6Al4V alloy blocks with a diameter of 1 cm and a height of 3 cm are bonded together with a sample. After curing for 15 min, the two are broken and separated from the joint using a universal testing machine at a speed of 1 mm / min. The stress-strain curve is obtained, and the maximum stress is the compressive shear strength.

[0062] In order to test the bonding stability, the test samples were immersed in water for 24 hours after curing for 15 minutes and then subjected to compression shear test. The number of test samples in each group was 3.

[0063] Experimental results are as follows Figure 2 As shown, after curing for 15 minutes, the group with a BG content of 5mg (B5O) was added. 30 T 95 P 60 The sample exhibited significantly higher compressive shear strength than other groups, reaching 5.3 MPa, demonstrating its superior adhesive stability compared to other groups.

[0064] Experimental results are as follows Figure 3 As shown, after soaking in water for 24 hours, B5O 30 T 95 P 60 The group achieved a compressive shear strength of 7.3 MPa, indicating that it exhibited bonding stability after immersion compared to the control group.

[0065] Example 5 Tensile separation test: Two Ti6Al4V alloy plates with a diameter of 2cm were bonded together with the sample. After the bond was cured for 15min, the two were separated by longitudinal stretching using a universal testing machine at a stretching speed of 1mm / min. The load-force curve was obtained, and the tensile strength was calculated according to the following formula (1): (1); P represents tensile strength, D is the diameter of the titanium plate, and N is the peak tensile force.

[0066] To test the bonding stability, the test samples were immersed in water for 24 hours after curing for 15 minutes and then subjected to tensile separation tests. The number of test samples in each group was 3.

[0067] Experimental results are as follows Figure 4 As shown, after curing for 15 minutes, B5O 30 T 95 P 60 The tensile strength of the sample group was significantly higher than that of the other groups, reaching 3.5 MPa, demonstrating that it exhibited higher tensile strength in a short time compared to the other groups of adhesives.

[0068] Experimental results are as follows Figure 5 As shown, after soaking in water for 24 hours, B5O 30 T 95 P 60 The group achieved a tensile strength of 3.9 MPa, indicating that it exhibited bonding stability after immersion compared to the control group.

[0069] Example 6 Adhesion performance test: using O 30 T 100 P 60 and B5O 30 T 95 P 60 Two rectangular bone blocks (1cm×1cm×2cm) were bonded together and cured for 15 minutes. Compression shear and tensile strength tests were then performed using a universal testing machine at a compression rate of 1mm / min. Each test was repeated three times to evaluate the short-term bone bond strength and bond stability of the adhesive.

[0070] Experimental results are as follows Figure 6 and Figure 7 As shown in the quantification, B5O30 T 95 P 60 The adhesive exhibits good compressive shear strength and tensile strength at the bone-bone interface. The compressive shear strength is 4.21 MPa and the tensile strength is 3.47 MPa.

[0071] Example 7 Compression strength test: B5O 30 T 95 P 60 The adhesive was used to create cylindrical samples with a diameter of 6 mm and a height of 4 mm using a silicone mold. After curing for 15 minutes, a universal testing machine was used to perform compression tests at a speed of 1 mm / min until the sample broke, obtaining the stress-strain curve. The maximum stress value was taken as the compressive strength of the sample. The samples were then immersed in SBF and placed in a 37°C constant temperature shaker. Their compressive strength was tested after 1, 3, and 7 days, with three samples tested each time.

[0072] Experimental results are as follows Figure 8 As shown, B5O 30 T 95 P 60 The adhesive SBF continued to cure after 1 and 3 days and maintained mechanical stability after 7 days. The compressive strengths at 1, 3, and 7 days were 84.75 MPa, 94.94 MPa, and 109.3 MPa, respectively.

[0073] Example 8 Morphology characterization by scanning electron microscopy (SEM): The freeze-dried sample was cut into small pieces, sputtered with gold on carbon conductive adhesive for 120 seconds, and the sample was photographed using a voltage of 10kV or 15kV.

[0074] X-ray diffraction (XRD): The freeze-dried sample is ground in a mortar and pestle, and an appropriate mass is placed on the XRD powder sample stage. The sample is tested in the range of 10° to 80°. The voltage is set to 40 kV, the current to 40 mA, the step size to 0.1°, and the time for each step to 1 s.

[0075] Experimental results are as follows Figure 9 As shown, B5O 30 T 95 P 60 The adhesive induced spindle-shaped hydroxyapatite crystals on the material surface after 7 days in simulated body fluid; with an extended culture time of 14 days, more mature spherical hydroxyapatite subsequently developed. Figure 10 XRD test results prove B5O 30 T 95 P 60 The adhesive has good mineralization ability.

[0076] Example 9 Cytotoxicity test: B5O was subjected to α-MEM complete medium. 30 T 95 P 60 After extraction, approximately 5,000 mouse embryonic osteoblast precursor cells were seeded in 96-well plates. Once the cells adhered, α-MEM complete medium and B5O were added, respectively. 30 T 95 P 60 The extract and positive control (0.1 g zinc diethyldithiocarbamate + 10 ml water) were cultured for 72 h. Then, CCK-8 reagent was added and incubated for 4 h. The absorbance was measured at 450 nm to investigate the cytotoxicity of the adhesive.

[0077] Experimental results are as follows Figure 11 As shown, B5O 30 T 95 P 60 The adhesive exhibits good biocompatibility and demonstrates a certain effect in promoting cell proliferation. CCK-8 results showed a 115.5% success rate at day 1.

[0078] Example 10 The difference between this embodiment and embodiment 1 is that the pH test in step (2) is changed to an alkaline phosphatase test, while the rest of the preparation process is the same as in embodiment 1, and a bioactive bone adhesive is obtained.

[0079] Osteogenic differentiation test: B5O was subjected to osteogenic differentiation using α-MEM complete medium. 30 T 95 P 60 After extraction, approximately 5,000 mouse embryonic osteoblast precursor cells were seeded in 96-well plates. Once the cells adhered, α-MEM complete medium and B5O were added, respectively. 30 T 95 P 60 The extract was cultured for 7 days. Alkaline phosphatase detection and staining were then performed.

[0080] Experimental results are as follows Figure 12 As shown, B5O 30 T 95 P 60 The adhesive exhibited excellent osteogenic properties, significantly enhancing the activity of alkaline phosphatase in osteoblasts. The quantified result was 0.1, significantly superior to other groups. Real-world data images show a clearer blue-purple result.

[0081] Example 11 The difference between this embodiment and embodiment 1 is that the pH test in step (2) is changed to a calcium matrix deposition test, while the rest of the preparation process is the same as in embodiment 1, and a bioactive bone adhesive is obtained.

[0082] Osteogenic differentiation test: B5O was subjected to osteogenic differentiation using α-MEM complete medium. 30 T 95 P 60 After extraction, approximately 5,000 mouse embryonic osteoblast precursor cells were seeded in 96-well plates. Once the cells adhered, α-MEM complete medium and B5O were added, respectively. 30 T 95 P 60 The extract was cultured for 14 days. Alizarin Red S staining and detection were then performed.

[0083] Experimental results are as follows Figure 13 As shown, B5O 30 T 95 P 60 The adhesive exhibited excellent osteogenic properties, significantly promoting calcium matrix deposition. The quantification result was 2.8, showing a significant difference compared to other groups. Real-world images showed denser calcium nodule formation. Example 12 The difference between this embodiment and embodiment 1 is that the pH test in step (2) is changed to a 12-week degradation test.

[0084] Prepare 200 mg adhesive samples with dimensions of 4 mm height and 6 mm diameter. Immerse the samples in 10 mL of freshly prepared SBF and place them in a constant temperature shaking incubator (37 ± 0.5 °C) for dynamic degradation experiments. Take samples every 7 days, gently rinse the surface ion deposits with ultrapure water, and freeze dry them to constant weight. Record the mass loss rate and calculate it using formula (2): (2) Where m0 is the initial mass, m t Let t be the mass at time t.

[0085] Experimental results are as follows Figure 14 As shown, B5O 30 T 95 P 60 The adhesive exhibited a progressive loss of mass, retaining approximately 64.08% of its initial mass at week 8 before beginning to disintegrate; by week 12, the remaining mass had decreased to approximately 22.50%, which matches the time lag of fracture healing.

[0086] Comparative Example 2 The difference between this comparative example and Example 1 is that the mass ratio of OPLS to TTCP mixture in step (1) is adjusted to 0.6, 0.5, and 0.4, the BG content is zero, the ratio of PAA to TTCP remains unchanged at 0.46, and the rest of the preparation process is the same as in Example 1. The adhesive is prepared and a compression shear test is performed after the titanium alloy block is bonded and cured for 15 minutes.

[0087] Test results are as follows Figure 15 As shown, the compressive shear strength of adhesives with OPLS to TTCP ratios of 0.6, 0.5, and 0.4 was significantly lower than that of 0.3, indicating that adhesives with a low OPLS ratio have better bonding performance.

[0088] Comparative Example 3 The difference between this comparative example and Example 1 is that the liquid-solid ratio in step (1) is adjusted to 0.3 and 0.38 respectively. The rest of the preparation process is the same as in Example 1. The adhesive is prepared and a compression shear test is performed after the titanium alloy block is bonded and cured for 15 minutes.

[0089] Test results are as follows Figure 16 As shown, the compressive shear strength of the adhesives with liquid-to-solid ratios of 0.3 and 0.38 was significantly lower than that of the 0.46 group, indicating that the adhesives with a high PAA ratio have better bonding performance.

[0090] Example 13 The difference from Example 1 is that PAA in step (1) is replaced with 80-150W 2% 45mgHA, 80-150W 1% wt 30mgHA, 80-150W 0.25% wt 30mgHA, 80-150W 0.5% wt 30mgHA, 40-80W 2.5% wt 30mgHA, and 10-20W 2.5% wt 30mgHA, respectively. The rest is the same as in Example 1. The adhesive is prepared and a compression shear test is performed after the titanium alloy block is bonded and cured for 15 minutes.

[0091] The results are as follows Figure 17 As shown, the compressive shear strength of the adhesive is 2.8~3.8 MPa, which is higher than the theoretical minimum service strength, and there is no significant difference under the same mass of sodium hyaluronate.

[0092] Comparative Example 4 The difference from Example 11 is that the 80-150W 1%wt 45mgHA in step (1) is replaced with 80-150W 2%wt 60mgHA. All other preparation processes are the same as in Example 10. The adhesive is prepared and a compression shear test is performed after the titanium alloy block is bonded and cured for 15 minutes.

[0093] The results are as follows Figure 17 As shown, excessively high sodium hyaluronate solution mass is detrimental to the compressive shear strength of the adhesive.

[0094] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the present invention.

Claims

1. A bioactive bone adhesive, characterized in that: include, Tetracalcium phosphate, The composition comprises o-phospho-L-serine, bioactive glass as a functional enhancing component, and a solution selected from aqueous polyacrylic acid solution or aqueous sodium hyaluronate solution; wherein the components are bonded to form a stable composite material through coordination bonds and ionic bonds between phosphate groups, carboxyl groups and calcium ions.

2. The bioactive bone adhesive as described in claim 1, characterized in that: The mass ratio of the total mass of o-phospho-L-serine to tetracalcium phosphate and bioactive glass is (0.3:1) to (0.6:1).

3. The bioactive bone adhesive as described in claim 2, characterized in that: The mass ratio of tetracalcium phosphate to bioactive glass is (5.6~19):

1.

4. The bioactive bone adhesive as described in claim 1, characterized in that: The mass ratio of the polyacrylic acid aqueous solution to all solid components, tetracalcium phosphate, o-phospho-L-serine, and bioactive glass, is (0.31:1) to (0.46:1).

5. The bioactive bone adhesive as described in claim 1, characterized in that: The mass ratio of the sodium hyaluronate aqueous solution to all solid components tetracalcium phosphate, o-phospho-L-serine, and bioactive glass is (0.23:1) to (0.46:1).

6. The bioactive bone adhesive as described in claim 5, characterized in that: The adhesive exhibits an initial adhesion strength of 3.57–5.72 MPa to titanium alloys after curing at room temperature for 15 minutes; and an initial adhesion strength of 6.10–7.56 MPa to titanium alloys after 24 hours of incubation in simulated body fluid.

7. The bioactive bone adhesive as described in claim 6, characterized in that: The adhesive maintains a compressive strength of 90.29 MPa to 113.93 MPa after being placed in a humid environment for 7 days.

8. The bioactive bone adhesive as described in claim 7, characterized in that: Cell viability was 101.64%–119.07% in CCK8 assay at day 1, ALP quantification at day 7 was 0.095–0.109, and Alizarin Red quantification at day 14 was 2.407–3.

326.

9. Use of the bioactive bone adhesive as described in any one of claims 1 to 8 for fracture fixation or bone defect repair.

10. A bone tissue engineering repair system, characterized in that: The invention includes, as described in any one of claims 1 to 8, a bioactive bone adhesive, and a medical titanium alloy implant; wherein the adhesive serves as an interface functional layer mediating the biomechanical integration and bioactive coupling between the implant and the host bone tissue.

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