A biomimetic hybrid nanocomposite scaffold and a preparation method and application thereof

Abstract

The present application relates to the technical field of biological stent, in particular to a kind of bionic hybrid nanocomposite stent and its preparation method and application.The bionic hybrid nanocomposite stent provided by the present application has excellent biological activity, antibacterial property and bone repair performance, by using the potential of antibiotic-free antibacterial nanoparticles (Sr-doped bioactive glass, SrBG) to resist infection in combination with microRNA-138 inhibitor, strontium and microRNA-138 can form synergistic effect, strengthen bioactivity and antibacterial property, and microRNA-based gene therapy stimulates osteogenesis and angiogenesis;In addition, made into PMMA bone cement not only increases the specific surface area of bioactive glass, but also the crosslinking of PMMA and gelatin makes PMMA more dispersed, thereby increasing the active substance action range, forming synergistic effect, thereby further improving the overall biological activity.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological scaffolds, and particularly relates to a biomimetic hybrid nanocomposite scaffold and a preparation method and application thereof. BACKGROUND

[0002] Bone graft materials in the process of bone regeneration may play the following roles according to their characteristics, including osteogenesis (new bone produced by living osteoblasts), osteoinduction (osteoblast differentiation to generate) and osteoconduction (bone growth along the material). In recent years, in the research of bone injury repair (especially critical bone defect repair), more and more attention has been paid to the construction of biomaterials that have good mechanical properties and can simulate bone conduction and osteoinduction behavior. The biomimetic performance of the material and the satisfaction of the clinical use scene are crucial for the selection of bone substitute biomaterials. The combination of biomaterials with other biological factors, the simulation of the natural bone microenvironment and the improvement of the performance of the scaffold, and the promotion of the integration of the bone substitute into the host system are important directions of the research. For example, in 1971, the combination of bone and bioactive glass and glass-ceramics was first published; in 1981, the combination of soft connective tissue and 45S5 bioactive glass was found; in 1981, toxicology and biocompatibility studies (in vitro and in vivo) were published to determine the safety of bioactive glass products; in 1987, the bone stimulating effect of bioactive glass particles in bone regeneration was found; in 2000, FDA approved solid bone for general orthopedic bone grafting in non-weight-bearing parts; in 2004, FDA approved 45S5 particles for treatment of dentin hypersensitivity (tea benzamine).

[0003] The development of new technologies for bone tissue engineering requires the production of macroporous scaffolds with bioactivity and biodegradability. Among the numerous existing bone replacement materials, hydroxyapatite (HA) ceramics are useful bone substitutes, but their degradation is minimal. Tricalcium phosphate is also an alternative bone replacement material, but it shows poor Ca-P formation ability in vitro and in vivo, although it is degradable.

[0004] Bioactive glass has been widely concerned based on its unique advantages, which is usually composed of calcium-containing silicate, among which calcium silicate (CaSiO3) is the earliest used for in vitro and in vivo bioactivity research. Compared with calcium phosphate, calcium silicate not only has good biocompatibility and biodegradability, but also gradually releases silicon ions and calcium ions, which activate the signal pathways related to bone mineralization, bone remodeling and angiogenesis, and accelerate the speed of bone regeneration.

[0005] However, not all kinds of bioactive glass are suitable for use as bone replacement materials. For example, mesoporous bioactive glass (MBG) has excellent bioactivity, biocompatibility and bone conductivity, and plays an important role in bone tissue regeneration, but it is difficult to prepare MBG scaffolds with high compressive strength for bone regeneration applications, which greatly hinders its development and use. Although creating glass scaffolds with lower overall porosity or smaller pore size can significantly improve the compressive strength, it may reduce its suitability for bone regeneration within the scaffold.

[0006] ‌45S5 bioactive glass is expected to be the first choice of bioactive glass material for producing macroporous scaffolds to meet the needs of the development of new technologies for bone tissue engineering due to its excellent bioactivity and biodegradability. However, it is difficult to prepare porous bioactive glass templates (scaffolds) for bone regeneration based on bioactive glass 45S5. If prepared by melting method, the melting method tends to result in the formation of low-purity products due to chemical heterogeneous substances and some contaminants, which may be caused by the primary crystallization process accompanied by precipitation or the presence of unreacted solid chemicals, specifically the crystallization of bioactive glass 45S5 during sintering; and the final bioactive glass powder has limited porosity and low specific surface area. If prepared by template method, although the template method is used to grow tubular channels in the material, it can increase the porosity of the obtained scaffold and enhance the gap network, but the higher porosity reduces the compressive strength. If prepared by sol-gel method, which is a preparation method using acid / alkali catalysis, acid / alkali catalysis synthesis is conducive to the use of strong inorganic acid as a catalyst for rapid hydrolysis reaction, and alkali catalysis promotes the formation of cross-linking and complex polymer structure, but it is difficult to obtain bioactive glass with controllable morphology and uniform particle size at the micro-nano level. Therefore, there are great difficulties in the process of preparing porous bioactive glass scaffolds for bone regeneration based on bioactive glass 45S5.

[0007] Moreover, in order to meet the development needs of new technologies for bone tissue engineering, the bio-scaffold is also required to have excellent bioactivity, antibacterial property and bone repair performance. In recent years, through surface functional coating modification, micro-nano structure or porous structure optimization, functional element / small molecule doping and blending composite, etc., the related researches on how to control the degradation rate of biomaterials and improve their bioactivity and osteogenic ability have attracted widespread attention. However, there is no clear guidance on how to prepare a bio-scaffold with excellent bioactivity, antibacterial property and bone repair performance. SUMMARY

[0008] Therefore, the technical problem to be solved by the present application is to provide a biomimetic hybrid nanocomposite scaffold and a preparation method and application thereof. The biomimetic hybrid nanocomposite scaffold provided by the present application has excellent bioactivity, antibacterial property and bone repair performance.

[0009] The application provides a kind of biomimetic hybrid nanocomposite scaffold, which is prepared by gelatin, microRNA-138 inhibitor, strontium-doped 45S5 bioactive glass and polymethyl methacrylate (PMMA);

[0010] The strontium-doped 45S5 bioactive glass and PMMA are used as bone cement components, and the mass ratio of the total mass of the two to the mass of the gelatin and the microRNA-138 inhibitor is 2:2:(0.8-1.2); and the mass ratio of the strontium-doped 45S5 bioactive glass to PMMA is (0.3-0.5):(0.5-0.7). In the strontium-doped 45S5 bioactive glass, the doping amount of strontium is (1-5) wt%.

[0011] The strontium-doped 45S5 bioactive glass is prepared from tetraethyl orthosilicate, triethyl phosphate, nitric acid, water, calcium nitrate, sodium nitrate and strontium nitrate; the surface of the strontium-doped 45S5 bioactive glass is further coated with hydroxyapatite to form a core-shell structure with the strontium-doped 45S5 bioactive glass as the core.

[0012] In the biomimetic hybrid nanocomposite scaffold provided by the application, on the one hand, the strontium-doped 45S5 bioactive glass forms a core-shell structure with hydroxyapatite, and then is made into bone cement with PMMA, which increases the specific surface area of the bioactive glass; on the other hand, the strontium in the strontium-doped 45S5 bioactive glass and the microRNA-138 synergize, which strengthens the bioactivity and antibacterial property and reduces the risk of infection at the filling site. In addition, the bone cement is crosslinked with the gelatin, which makes the PMMA more dispersed, thereby increasing the action range of the active substances and forming a synergistic effect, so as to further improve the overall bioactivity.

[0013] The application further provides a preparation method of the biomimetic hybrid nanocomposite scaffold according to any one of the technical solutions described above, which comprises the following steps: mixing gelatin, microRNA-138 inhibitor, strontium-doped 45S5 bioactive glass and PMMA, then freeze-drying, and then crosslinking in a crosslinking agent to obtain the biomimetic hybrid nanocomposite scaffold.

[0014] Specifically, the application first combines strontium-doped 45S5 bioactive glass and PMMA to obtain bone cement; then mixes the bone cement in a water solution of microRNA-138 inhibitor and gelatin to form a gel to obtain a formed material after gelation at (0~4) ℃ overnight; then freeze-dries the formed material; and finally soaks the freeze-dried material in a crosslinking agent solution to crosslink, to obtain a biomimetic hybrid nanocomposite scaffold. The freeze-drying is specifically: first freezing at (-30~-10) ℃ for (46~50) h, then freezing at (-90~-70) ℃ for (22~26) h, and finally freeze-drying at (-60~-40) ℃ for (46~50) h. The crosslinking temperature is room temperature, specifically (20~30) ℃, preferably 25 ℃; and the crosslinking time is (22~26) h. The crosslinking agent is at least one selected from glutaraldehyde, genipin, anthocyanin, and hexamethylene diisocyanate. The amounts of the gelatin, microRNA-138 inhibitor, strontium-doped 45S5 bioactive glass, and PMMA are the same as described above, and will not be repeated. The biomimetic hybrid nanocomposite scaffold obtained by the application is the same as described above, and will not be repeated.

[0015] The strontium-doped 45S5 bioactive glass is prepared by the following steps: hydrolysis of 45S5 bioactive glass, tetraethyl orthosilicate, nitric acid and water, then polycondensation of the obtained material and triethyl phosphate, and then static aging of the obtained material mixed with calcium nitrate, sodium nitrate and strontium nitrate. Specifically, the 45S5 bioactive glass and tetraethyl orthosilicate are sequentially added into an aqueous nitric acid solution for hydrolysis, then triethyl phosphate is added into the obtained material for polycondensation, and then calcium nitrate, sodium nitrate and strontium nitrate are added into the obtained material at intervals of (18-22) min, and then static aging is performed to obtain the strontium-doped 45S5 bioactive glass. The amount of tetraethyl orthosilicate, nitric acid and water is (14-18) mL:(1-2) mL:(15-25) mL, the amount of triethyl phosphate is (0.1-1) mL, and the amount of calcium nitrate, sodium nitrate and strontium nitrate is (8-12) g:(5-7) g:(0.4-2.5) g, based on 10 g of 45S5 bioactive glass. The hydrolysis temperature is (20-30) ℃, and the hydrolysis time is (50-70) min; the polycondensation temperature is (20-30) ℃, and the polycondensation time is (20-30) min; and the static aging time is (90-100) h. After the static aging, the present application further includes drying, specifically: drying at (65-75) ℃ for (22-26) h, and then drying at (110-130) ℃ for (46-50) h.

[0016] The present application also provides the application of the biomimetic hybrid nanocomposite scaffold of any of the above technical solutions or the biomimetic hybrid nanocomposite scaffold prepared by the preparation method of any of the above technical solutions as a hard tissue repair material, a soft tissue repair material, a vascular stent or an artificial joint prosthesis.

[0017] The application provides a kind of bionic hybrid nanocomposite scaffold and its preparation method and application.The application uses freeze-drying method to prepare new hybrid nanocomposite based on gelatin / microRNA-138 inhibitor / Sr doped 45S5 bioactive glass nanoparticles crosslinked PMMA, by using the potential of antibiotic-free antibacterial nanoparticles (Sr doped bioactive glass, SrBG) combined with microRNA-138 inhibitor to resist infection, strontium and microRNA-138 can form synergistic effect, strengthen bioactivity and antibacterial property, and microRNA-based gene therapy stimulates osteogenesis and angiogenesis; In addition, it is made into PMMA bone cement, not only increases the specific surface area of bioactive glass, but also makes PMMA more dispersed by crosslinking PMMA with gelatin, thereby increasing the active substance action range, forming synergistic effect, thereby further improving the overall bioactivity.

[0018] Experiments show that the application combines microRNA-138 inhibitor and strontium with composite bioactive glass to form a bionic hybrid nanocomposite scaffold with good anti-infective performance and bioactivity. Specifically, the addition of strontium element and microRNA inhibitor has a synergistic effect, 45S5 bioactive glass forms a core-shell structure with hydroxyapatite, and is prepared into PMMA cement dispersed in gelatin, and the three processes form a synergistic effect, enhancing the related performance; The number of living cells on the surface of strontium and microRNA inhibitor modified PMMA bioactive glass increased by 2 times after 48 h, and the synergistic effect of microRNA-138 inhibitor in the composite scaffold is obviously better than that of other similar inhibitors. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The bioactivity test diagram of the microspheres obtained by adding 0 g of strontium nitrate;

[0020] Figure 2 The bioactivity test diagram of the microspheres obtained by adding 0.46 g of strontium nitrate;

[0021] Figure 3 The bioactivity test diagram of the microspheres obtained by adding 1.38 g of strontium nitrate;

[0022] Figure 4 The bioactivity test diagram of the microspheres obtained by adding 2.31 g of strontium nitrate;

[0023] Figure 5 The bioactivity diagram of the bionic nanocomposite scaffold obtained by the present application comparative example 1;

[0024] Figure 6The bioactivity graph of the biomimetic nanocomposite scaffold obtained for Invention Comparative Example 2. DETAILED DESCRIPTION

[0025] The present application discloses a kind of biomimetic hybrid nanocomposite scaffold and its preparation method and application.The person skilled in the art can improve process parameters with reference to the content of this paper, realize it is appropriate.For special need, all similar substitutions and changes are obvious to the person skilled in the art, and they are regarded as including in the present application.The method and application of the present application have been described by preferred embodiment, and the relevant personnel can obviously change or appropriately change and combine the method and application of this paper without departing from the content, spirit and scope of the present application, to realize and apply the present application technology.

[0026] The present application studies the performance of bioactive glass and scaffold by the following method:

[0027] (1) by Fourier transform infrared spectroscopy (FTIR) to the sample before and after soaking, the bioactivity of bioactive glass in simulated body fluid (SBF) is studied.

[0028] (2) the antibacterial performance of composite bioactive glass and biomimetic hybrid nanocomposite scaffold is studied.

[0029] (3) the influence of composite bioactive glass scaffold on proliferation, osteogenic differentiation, angiogenic potential is studied, specifically in vitro osteogenic activity and in vitro vascular activity detection.

[0030] Among them, in vitro osteogenic activity detection reference: interspersed mesenchymal stem cells (BMSCs) are seeded at the bottom of 24-well plate, and 5 mg scaffold sample is embedded in the upper part of Transwell system. Both cells and scaffolds are soaked in osteogenic induction medium (50 μg / mL ascorbic acid, 10 nM dexamethasone and 10 mM β-glycerophosphate), and the medium is replaced every other day. After 7 days of culture, the expression of osteogenic genes is quantitatively evaluated, including Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), ALP and Osterix. Cell lysis and total RNA extraction are carried out using TRIzol reagent (Invitrogen, USA). Then the extracted RNA is reverse transcribed into complementary DNA (cDNA) using a commercial kit (Takara, Japan) and subjected to RT-PCR quantitative analysis, and Table 1 lists the specific primer sequences used.

[0031] Table 1

[0032]

[0033] In vitro vascularization activity assay reference: Using scratch test to measure, the bone marrow mesenchymal stem cells (BMSCs) were cultured in the lower chamber of the transwell system, and the scaffold was placed in the upper chamber for subsequent detection. After the cells confluence, uniform scratch was performed using 200 μL pipette tip to evaluate the migration of BMSCs, and then the images were collected by Image J software after 24 hours for quantitative evaluation.

[0034] The present application is further illustrated in conjunction with the following examples:

[0035] Example 1

[0036] Preparation of novel hybrid nanocomposites based on gelatin / microRNA-138 inhibitor / Sr-doped 45S5 bioactive glass nanoparticles:

[0037] (1) Preparation of bioactive glass-hydroxyapatite (SrBG&HA) microspheres with different strontium doping amounts:

[0038] ① Preparation of microspheres with 0 g of strontium nitrate addition:

[0039] Step 1: Bioactive glass (BG) particles were synthesized by sol-gel method. 0.5 mL of nitric acid (HNO3, 65%) was added to 19.5 mL of distilled water (H2O) and stirred for 10 min. Then 10 g of the above-synthesized bioactive glass and 16.7 mL of tetraethyl orthosilicate (TEOS, Si(OC2H5)4) were added to the acidic solution in sequence, and the acid hydrolysis was carried out at room temperature (25°C) for 1 hour with stirring. 1.5 mL of triethyl phosphate (TEP, (C2H5)3PO4) was added, and the condensation was continued at room temperature (25°C) for 25 min with stirring.

[0040] Step 2: Then, 10.5 g of calcium nitrate (Ca(NO3)2) and 6.72 g of sodium nitrate (NaNO3) were added to each component with a time interval of 20 min. Then the whole material was stirred for 1 hour and stored at room temperature for 96 hours. After 96 h, the obtained gel was first placed in an oven at 70°C for 24 h, and then at 120°C for 48 h, obtaining microspheres with strontium-doped bioactive glass (SrBG) as the core and hydroxyapatite (HA) as the shell. The final microspheres had a strontium doping amount of 0 wt%.

[0041] ② Preparation of microspheres with 0.46 g of strontium nitrate addition:

[0042] Prepared according to the method of ①, and the only difference from ① is that in step 2, 10.5 g of calcium nitrate (Ca(N03)2) and 6.45 g of sodium nitrate (NaN03) and 0.46 g of strontium nitrate (Sr(N03)2) were added, respectively. The strontium doping amount in the final obtained microspheres is 1 wt%.

[0043] ③Preparation of microspheres with strontium nitrate addition amount of 1.38 g:

[0044] Prepared according to the method of ①, and the only difference from ① is that in step 2, 10.5 g of calcium nitrate (Ca(N03)2) and 5.9 g of sodium nitrate (NaN03) and 1.38 g of strontium nitrate (Sr(N03)2) were added, respectively. The strontium doping amount in the final obtained microspheres is 3 wt%.

[0045] ④Preparation of microspheres with strontium nitrate addition amount of 2.31 g:

[0046] Prepared according to the method of ①, and the only difference from ① is that in step 2, 10.5 g of calcium nitrate (Ca(N03)2) and 5.35 g of sodium nitrate (NaN03) and 2.31 g of strontium nitrate (Sr(N03)2) were added, respectively. The strontium doping amount in the final obtained microspheres is 5 wt%.

[0047] The above obtained microspheres with different strontium doping amounts were cultured in SBF solution to test their biological activity and antibacterial properties, wherein sample 0 represents the microspheres with strontium nitrate addition amount of 0 g, sample 1 represents the microspheres with strontium nitrate addition amount of 0.46 g, sample 2 represents the microspheres with strontium nitrate addition amount of 1.38 g, and sample 3 represents the microspheres with strontium nitrate addition amount of 2.31 g. The biological activity of each obtained microspheres is shown in Figures 1-4 Figure 1 the biological activity test diagram of the microspheres with strontium nitrate addition amount of 0 g, Figure 2 the biological activity test diagram of the microspheres with strontium nitrate addition amount of 0.46 g, Figure 3 the biological activity test diagram of the microspheres with strontium nitrate addition amount of 1.38 g, Figure 4 the biological activity test diagram of the microspheres with strontium nitrate addition amount of 2.31 g; and the antibacterial properties of each obtained microspheres are shown in Table 2.

[0048] Table 2

[0049]

[0050] (2) Preparation of SrBG&HA-containing PMMA cement:

[0051] SrBG&HA microspheres with strontium nitrate addition amount of 1.38 g were prepared by the method in (1).​

[0052] The microspheres were mixed with PMMA together to prepare the PMMA cement doped with 40 wt% SrBG&HA microspheres.

[0053] (3) Preparation of the biomimetic hybrid nanocomposite scaffold:

[0054] The scaffold was prepared by freeze-drying method. The gelatin aqueous solution prepared at 25℃ was mixed with the PMMA cement doped with 40 wt% SrBG&HA microspheres, gelatin and microRNA-138 inhibitor at a mass ratio of 2:2:1. The microRNA inhibitor was added into the gelatin solution and stirred for 10 min. Then the PMMA cement doped with 40 wt% SrBG&HA microspheres obtained in (2) was added into the gelatin solution and stirred for 1.5 h. After that, the mixture was shaped and gelled at 2℃ overnight. The shaped material was first frozen at -20℃ for 48 h, and then transferred to -80℃ for further freezing for 24 h. Subsequently, the nanocomposite was freeze-dried in a freeze-drying machine at -50℃ for 48 h to obtain the porous nanocomposite. Then the sample was immersed in a 0.5% glutaraldehyde ethanol solution (% capacity / volume) for 24 hours for crosslinking to obtain the biomimetic hybrid nanocomposite scaffold.

[0055] The biomimetic hybrid nanocomposite scaffold was tested for bioactivity, antibacterial property, slow-release duration, in-vitro osteogenic activity and in-vitro vascular activity. The bioactivity can be seen from Figure 3 (the bioactivity spectrum is consistent because the scaffold and the microspheres only differ in dispersion method), the slow-release duration (the duration of slow release of effective components) is 22 d, and the antibacterial property, in-vitro osteogenic activity and in-vitro vascular activity are shown in Table 3.

[0056] Table 3

[0057]

[0058] Comparative Example 1

[0059] The PMMA cement containing SrBG&HA was prepared according to the same method as Example 1 to obtain the PMMA cement doped with 40 wt% SrBG&HA microspheres.

[0060] The scaffold was prepared using freeze-drying method. The gelatin aqueous solution was prepared at 25 °C, and the PMMA cement doped with 40 wt% SrBG&HA microspheres was added to the gelatin solution, and stirred for 1.5 h. Then the mixture was shaped and gelled at 2 °C overnight. The shaped material was first frozen at -20 °C for 48 h, and then transferred to -80 °C for further freezing for 24 h to obtain the nanocomposite. Subsequently, the nanocomposite was freeze-dried in a freeze-dryer at -50 °C for 48 h to obtain the porous nanocomposite. Then the sample was immersed in 0.5% glutaraldehyde ethanol solution (% capacity / volume) for 24 hours for crosslinking to obtain the biomimetic nanocomposite scaffold.

[0061] The biological activity, antibacterial property, slow-release duration, in-vitro osteogenic activity and in-vitro vasculogenic activity were tested, wherein the biological activity was shown in Table 4, the antibacterial property, the in-vitro osteogenic activity and the in-vitro vasculogenic activity were shown in Table 4. Figure 5 Figure 5 The biological activity of the biomimetic nanocomposite scaffold obtained from Comparative Example 1 was shown in Table 4; the slow-release duration (the duration of slowly releasing effective components) was 22 d, and the antibacterial property, the in-vitro osteogenic activity and the in-vitro vasculogenic activity were shown in Table 4.

[0062] Table 4

[0063]

[0064] Comparative Example 2

[0065] The PMMA cement containing SrBG&HA was prepared according to the same method as Example 1 to obtain the PMMA cement doped with 40 wt% SrBG&HA microspheres.

[0066] The scaffold was prepared using freeze-drying method. The gelatin aqueous solution was prepared at 25 °C, and the PMMA cement doped with 40 wt% SrBG&HA microspheres was added to the gelatin solution, and stirred for 1.5 h. Then the mixture was shaped and gelled at 2 °C overnight. The shaped material was first frozen at -20 °C for 48 h, and then transferred to -80 °C for further freezing for 24 h to obtain the nanocomposite. Subsequently, the nanocomposite was freeze-dried in a freeze-dryer at -50 °C for 48 h to obtain the porous nanocomposite. Then the sample was immersed in 0.5% glutaraldehyde ethanol solution (% capacity / volume) for 24 hours for crosslinking to obtain the biomimetic nanocomposite scaffold.

[0067] The biological activity, antibacterial property, slow-release duration, in-vitro osteogenic activity and in-vitro vasculogenic activity were tested, wherein the biological activity was shown in Table 4, the antibacterial property, the in-vitro osteogenic activity and the in-vitro vasculogenic activity were shown in Table 4. Figure 6 Figure 6 ​​The bioactivity graph of the biomimetic nanocomposite scaffold obtained in Inventive Example 2 has a slow-release duration (the duration of slow release of effective components) of 22 days, and the antibacterial property, in-vitro osteogenic activity and in-vitro vascular survival activity are shown in Table 5.

[0068] Table 5

[0069]

[0070] It is found through characterization of the synthesized bioactive glass that doping 3 wt% of strontium Sr in the structure of the 45S5 bioactive glass prepared by sol-gel method optimizes the biocompatibility and antibacterial property thereof. In addition, it is observed that the bioactive glass has antibacterial property against both gram-positive bacteria and gram-negative bacteria. It can be seen that the combination of the bioactive glass and the microRNA-138 inhibitor can improve cell activity and cell adhesion.

[0071] The above merely provides the preferred embodiments of the present application, but the protection scope of the present application is not limited thereto, and any person skilled in the art, according to the technical solution and the inventive concept of the present application, can make equivalent replacement or change within the technical range disclosed by the present application, which should be covered within the protection scope of the present application.

Claims

1. A biomimetic hybrid nanocomposite scaffold, characterized in that, The biomimetic hybrid nanocomposite scaffold is prepared from gelatin, microRNA-138 inhibitor, strontium-doped 45S5 bioactive glass and PMMA.

2. The biomimetic hybrid nanocomposite scaffold of claim 1, wherein, The mass ratio of the strontium-doped 45S5 bioactive glass and PMMA to the gelatin and the microRNA-138 inhibitor is 2:2:(0.8-1.2). The mass ratio of the strontium-doped 45S5 bioactive glass and PMMA is (0.3-0.5):(0.5-0.7).

3. The biomimetic hybrid nanocomposite scaffold of claim 1, wherein, The doping amount of strontium in the strontium-doped 45S5 bioactive glass is (1-5) wt%.

4. The biomimetic hybrid nanocomposite scaffold of claim 1, wherein, The surface of the strontium-doped 45S5 bioactive glass is coated with hydroxyapatite.

5. A method for preparing a biomimetic hybrid nanocomposite scaffold, characterized in that, The method comprises the following steps: The gelatin, microRNA-138 inhibitor, strontium-doped 45S5 bioactive glass and PMMA are mixed and formed, then freeze-dried, and cross-linked in a cross-linking agent to obtain the biomimetic hybrid nanocomposite scaffold.

6. The production method according to claim 5, wherein The mass ratio of the strontium-doped 45S5 bioactive glass and PMMA to the gelatin and the microRNA-138 inhibitor is 2:2:(0.8-1.2). The mass ratio of the strontium-doped 45S5 bioactive glass and PMMA is (0.3-0.5):(0.5-0.7).

7. The preparation method according to claim 5, characterized in that, The doping amount of strontium in the strontium-doped 45S5 bioactive glass is (1-5) wt%.

8. The preparation method according to claim 5, characterized in that, The strontium-doped 45S5 bioactive glass is prepared by the following steps: The 45S5 bioactive glass, tetraethyl orthosilicate, nitric acid and water are hydrolyzed, then the obtained materials and triethyl phosphate are subjected to polycondensation, and then the obtained materials, calcium nitrate, sodium nitrate and strontium nitrate are mixed and aged to obtain the strontium-doped 45S5 bioactive glass.

9. The production method according to claim 8, characterized by, The hydrolysis temperature is (20-30) ℃, and the hydrolysis time is (50-70) min. The polycondensation temperature is (20-30) ℃, and the polycondensation time is (20-30) min. The aging time is (90-100) h.

10. The use of the biomimetic hybrid nanocomposite scaffold of any one of claims 1-4 or the biomimetic hybrid nanocomposite scaffold prepared by the method of any one of claims 5-9 in the preparation of hard tissue repair material, soft tissue repair material, vascular stent or artificial joint prosthesis.

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