Preparation of bismuth-polydopamine composite scaffold based on 3D printing and application of bismuth-polydopamine composite scaffold in antibiosis and anti-inflammation

Abstract

The invention discloses preparation of a bismuth-polydopamine composite scaffold based on 3D printing and application of the bismuth-polydopamine composite scaffold in antibiosis and anti-inflammation. According to the preparation method, biodegradable polycaprolactone (PCL) is taken as a matrix, bismuth particles (Bi / PDA) coated with polydopamine are taken as a functional filler to be uniformly dispersed into the PCL matrix, and the Bi / PDA-PCL stent is prepared and formed through 3D printing. The Bi / PDA-PCL stent has structural stability, long-term antibacterial property and immune regulation and control functions, is suitable for various implantation scenes such as orthopedics department, stomatology department, soft tissue repair and the like, and provides a novel degradable biological material for implant infection prevention and treatment and tissue repair.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of biomedical and tissue engineering, and particularly relates to a preparation of a bismuth-polydopamine composite scaffold based on 3D printing and application thereof in antibacterial and anti-inflammatory. BACKGROUND

[0002] Polycaprolactone (PCL) and other degradable polymers are widely used in 3D printing of personalized scaffolds due to their good biocompatibility and moldability. However, the existing PCL-based scaffolds have the following technical bottlenecks: (1) lack of antibacterial properties, which is easy to be invaded by bacteria in the early stage of implantation and cause infection; (2) surface hydrophobicity and interface inertness, which leads to insufficient cell adhesion and tissue integration; (3) limited mechanical properties, which is difficult to balance structural stability and biological function under load conditions. These problems make it difficult for PCL-based implants to meet the integrated needs of "structural support-anti-infection-anti-inflammatory".

[0003] In the prior art, researchers have tried to improve antibacterial properties by adding bismuth oxide (Bi2O3, BiVO4, etc.) or other inorganic fillers, but there are the following shortcomings: (1) bismuth compounds containing anions are prone to release by-products during degradation, which may cause potential cytotoxicity; (2) the interface bonding force between the fillers and the polymers after compounding is weak, which leads to uneven dispersion and reduced mechanical properties; (3) the release behavior is difficult to control, and the antibacterial period is short and lacks anti-inflammatory regulation ability.

[0004] In addition, some studies have used dopamine (PDA) surface coating to improve the hydrophilicity and cell adhesion properties of PCL scaffolds, thereby improving their biocompatibility. However, PDA modification alone still has the following limitations: (1) the stability of PDA coating is limited and it is easy to fall off in body fluids or under mechanical load; (2) PDA has certain antioxidant activity, but lacks direct antibacterial ability and is difficult to inhibit bacterial invasion for a long time; (3) the phenolic hydroxyl / quinone structure of PDA is prone to partial inactivation under high-temperature printing or melting compounding conditions, making it difficult to maintain stable function in additive manufacturing systems.

[0005] Therefore, the development of a new degradable biomaterial with structural stability, long-term antibacterial properties, and immune regulation function provides a new strategy for implant infection prevention and tissue repair. SUMMARY

[0006] The first object of the present application is to overcome the shortcomings and deficiencies of the prior art, and to provide a Bi / PDA-PCL nanocomposite material using Bi / PDA particles as fillers.

[0007] The second object of the present application is to provide a preparation method of the Bi / PDA-PCL nanocomposite material.

[0008] A third object of the present application is to provide an application of the Bi / PDA-PCL nanocomposite.

[0009] A fourth object of the present application is to provide a Bi / PDA-PCL scaffold based on 3D printing.

[0010] A fifth object of the present application is to provide an application of the Bi / PDA-PCL nanocomposite or the Bi / PDA-PCL scaffold based on 3D printing.

[0011] The objects of the present application are achieved by the following technical solutions: A Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers, comprising the following components in percentage by mass: 1-10% of Bi / PDA particles, 90-99% of polycaprolactone (PCL); wherein, The polycaprolactone (PCL) is obtained by mixing polycaprolactone with number average molecular weight (Mn) of 2 kDa and 80 kDa at a mass ratio of (2-4):(6-8).

[0012] Preferably, the amount of Bi / PDA particles is 5-10% by mass; more preferably 10% by mass.

[0013] Preferably, the polycaprolactone (PCL) is obtained by mixing polycaprolactone with number average molecular weight (Mn) of 2 kDa and 80 kDa at a mass ratio of (3-4):(6-7).

[0014] Further preferably, the polycaprolactone (PCL) is obtained by mixing polycaprolactone with number average molecular weight (Mn) of 2 kDa and 80 kDa at a mass ratio of 3.5:6.5.

[0015] More preferably, the polycaprolactone (PCL) is 20-40 wt% (preferably 30-40 wt%; more preferably 35 wt%) of 2 kDa PCL and 60-80 wt% (preferably 60-40 wt%; more preferably 65 wt%) of 80 kDa PCL, based on a total amount of 100%.

[0016] Preferably, the Bi / PDA particles are prepared by the following method: Bi particles are added to a buffer solution, ultrasonically dispersed and mixed uniformly, purged with nitrogen to remove dissolved oxygen, then dopamine monomers are added, stirred and reacted, centrifuged and washed, and dried to obtain Bi / PDA particles.

[0017] Preferably, the mass ratio of Bi particles to dopamine monomers is (3-8):1; more preferably 5:1.

[0018] Preferably, the buffer solution is a PBS buffer solution.

[0019] Preferably, the buffer solution is used in an amount of 80-120 ml (more preferably 100 ml) per 50 mg of Bi particles.

[0020] Preferably, the ultrasonic dispersion is performed for 5-10 min.

[0021] Preferably, the nitrogen purging is performed for 8-12 min; more preferably, for 10 min.

[0022] Preferably, the stirring reaction is performed at a stirring rate of 600-850 r / min for 0.5-1.5 h.

[0023] More preferably, the stirring reaction is performed at a stirring rate of 750 r / min for 1 h.

[0024] Preferably, the centrifugation is performed at a centrifugal speed of 6000-14000 rpm for 10-50 min.

[0025] More preferably, the centrifugation is performed at a centrifugal speed of 11000 rpm for 30 min.

[0026] Preferably, the washing is performed using a solution obtained by mixing deionized water and ethanol at a volume ratio of 1:1.

[0027] Preferably, the drying is performed at a temperature of 40-80 ℃; more preferably, at 60 ℃.

[0028] Preferably, the Bi particles are obtained by a solvothermal reduction reaction using bismuth nitrate pentahydrate (Bi(NO3)3·5H2O) as a precursor, and are prepared by the following method: Under nitrogen protection, Bi(NO3)3·5H2O is dissolved in ethylene glycol to form a uniform colorless solution, which is vacuumed, and then the solution is placed in a closed condition at 150-240 ℃ (preferably at 170-220 ℃, more preferably at 200 ℃) for reaction. After the reaction is completed, the solution is cooled to room temperature, washed, and dried to obtain Bi particles.

[0029] Preferably, the mass ratio of Bi(NO3)3·5H2O to ethylene glycol is 1:10-15; more preferably, 1:13.7.

[0030] Preferably, the vacuuming is performed by purging nitrogen and then vacuuming to liquid boiling, which is repeated for 5 times.

[0031] Preferably, the reaction is carried out in a stainless steel hydrothermal reactor with a tetrafluoroethylene lining.

[0032] Preferably, the reaction time is 4-24 h.

[0033] Further preferably, the reaction time is 4-8 h; more preferably 6 h.

[0034] Preferably, the centrifugation is carried out at a speed of 6000-14000 r / min for 5-20 min.

[0035] More preferably, the centrifugation is carried out at a speed of 8000 r / min for 10 min.

[0036] Preferably, the washing is carried out using a solution obtained by mixing deionized water and ethanol at a volume ratio of 1:1.

[0037] Preferably, the drying is carried out at a temperature of 40-80℃; more preferably 60℃.

[0038] The method for preparing the Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers comprises the following steps: Dissolve polycaprolactone (PCL) and Bi / PDA particles in tetrahydrofuran (THF), stir and mix uniformly, then pour into a mold, dry under ventilation (remove the solvent), and obtain the Bi / PDA-PCL nanocomposite.

[0039] Preferably, the polycaprolactone (PCL) can be first mixed uniformly with tetrahydrofuran (which can be assisted by ultrasonic dispersion, such as ultrasonic dispersion for 5 min), and the Bi / PDA particles can be first dissolved in tetrahydrofuran, then magnetically stirred until completely dissolved, and then the two are stirred and mixed uniformly.

[0040] Preferably, the amount of tetrahydrofuran (THF) used is 5-10 ml per gram of raw material (polycaprolactone (PCL) and Bi / PDA particles).

[0041] Preferably, the stirring is carried out at a rate of 750 r / min for 2-4 h.

[0042] Preferably, the drying can be carried out first in a normal-temperature fume hood overnight, and then in a vacuum oven for further drying.

[0043] More preferably, the drying is carried out at a temperature of 40-60℃ for ≥24 h.

[0044] A 3D printing based Bi / PDA-PCL scaffold is obtained by 3D printing of the Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers; preferably, the Bi / PDA-PCL nanocomposite is prepared by the following method: using a 3D printer, controlling the temperature of the printer barrel to be 60-90 DEG C (preferably 65-75 DEG C; more preferably 70 DEG C), the extrusion gas pressure to be 200-600 kPa (preferably 300-500 kPa; more preferably 400 kPa), and observing that the printer barrel is continuous in shape, and then completing the 3D printing according to the set printing path.

[0045] Preferably, the 3D printer is sterilized before printing, for example, by spraying 75% alcohol and sterilizing with ultraviolet light.

[0046] Preferably, the 3D printer is an extrusion type 3D printer.

[0047] Preferably, the diameter of the printing needle of the 3D printer is 0.2-0.6 mm.

[0048] Further preferably, the diameter of the printing needle of the 3D printer is 0.3-0.5 mm; more preferably 0.4 mm.

[0049] Preferably, the size of the Bi / PDA-PCL scaffold is: diameter 3-10 mm, height 0.5-5 mm.

[0050] More preferably, the size of the Bi / PDA-PCL scaffold is: diameter 5 mm, height 1 mm.

[0051] The Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers and / or the 3D printing based Bi / PDA-PCL scaffold are used in the preparation of antibacterial, anti-inflammatory and / or tissue repair products.

[0052] The bacteria include Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and the like.

[0053] The products include in vitro antibacterial drugs, anti-inflammatory drugs, or implant scaffolds for orthopedics, dentistry and / or soft tissue repair.

[0054] The functional mechanism and technical effect of the present application are as follows: The present application uses biodegradable polycaprolactone (PCL) as a matrix, and introduces metal bismuth nanoparticles (Bi / PDA) coated with polydopamine (PDA) into the PCL matrix to construct a nanocomposite system with interface level integration characteristics. Metal bismuth (Bi) as a functional filler can release Bi 3+ions, which can destroy the bacterial cell wall structure, inhibit the activity of metabolic enzymes and induce the accumulation of reactive oxygen species (ROS), thereby achieving antibacterial effect; at the same time, Bi 3+ can interact with cell membrane proteins and inflammatory signaling pathway molecules to reduce the inflammatory response caused by bacterial endotoxins. The polydopamine coating layer plays a multiple interface regulation role in the system: first, the hydroxyl (-OH) and amino (-NH) functional groups on the surface of PDA can form a hydrogen bond network with the carbonyl (C=O) of PCL, improving the interfacial bonding force and dispersion stability between the filler and the polymer matrix, thereby enhancing the overall mechanical properties of the scaffold; second, PDA can act as a dynamic interface layer to regulate the release rate of Bi 3+ , inhibit the initial ion burst release and maintain a stable effective concentration to achieve sustained antibacterial activity; third, the phenolic hydroxyl / quinone structure in PDA has antioxidant activity, which can scavenge excess ROS, reduce oxidative stress damage and maintain the intracellular redox balance. Through the above synergistic mechanisms, Bi and PDA form an integrated system of "ion release - interface antioxidant - biological signal regulation" at the nanometer interface, enabling the scaffold to have synergistic antibacterial and anti-inflammatory effects; at the same time, the multiscale synergistic effect of Bi / PDA and PCL molecular chains significantly improves the wettability, mechanical strength and biocompatibility of the material. The interface-level synergistic effect enables the 3D printed Bi / PDA-PCL scaffold to have structural stability, long-term antibacterial properties and immune regulation functions, providing a new degradable biomaterial design strategy for implant infection prevention and tissue repair.

[0055] The present application has the following advantages and effects compared with the prior art: (1) The present application prepares a 3D printed scaffold integrated with anti-infection and tissue repair: the present application first proposes to combine polydopamine-coated bismuth nanoparticles (Bi / PDA) and polycaprolactone (PCL), and evenly disperses the polydopamine-coated bismuth nanoparticles (Bi / PDA) as functional fillers in the PCL matrix, and prepares a mold through fused deposition modeling (FDM) 3D printing to realize the synchronous integration of structural support, antibacterial and anti-infection, and anti-inflammatory regulation. The scaffold not only has good molding precision and mechanical strength, but also can form a sustained antibacterial and immune regulation microenvironment in vivo, overcoming the shortcomings of traditional PCL scaffolds that only have structural support and lack biological functions.

[0056] (2) The process is simple, controllable and suitable for large-scale production: the Bi / PDA-PCL composite material is prepared by solution dispersion combined with melt extrusion method, the process route is simple, the raw materials are stable and the repeatability is high. By optimizing the molecular weight ratio of PCL and printing parameters, good melt flowability and interlayer welding strength are realized, so that the composite scaffold has high fidelity and batch processing potential. Compared with traditional metal coating or drug impregnation method, no complex surface treatment steps are needed, which significantly reduces the production cost and biological safety risk.

[0057] (3) The invention constructs an interface coordination mechanism to achieve long-term antibacterial and anti-inflammatory regulation: the PDA shell provides rich -OH / -NH functional groups (which endows the material with controlled Bi 3+ slow release and interface hydrophilization), which can form a hydrogen bond network with the PCL molecular chain, enhance the interface compatibility, dispersibility and load transfer capacity, thereby improving the mechanical stability of the scaffold on a macroscopic scale, inhibiting bacterial adhesion and biofilm formation, and regulating the inflammatory microenvironment. At the same time, PDA controls the slow release process of Bi 3+ , forming a stable antibacterial concentration interval; it has the ability to resist oxidation and scavenge reactive oxygen species (ROS), and has a synergistic effect with Bi 3+ antibacterial effect, inhibiting bacterial adhesion in the early stage of implantation, relieving inflammation and promoting tissue healing in the later stage. This multi-dimensional coordination mechanism enables the scaffold to have long-term antibacterial and immunoregulatory dual functions. In vitro and in vivo evaluation shows that the scaffold has good biocompatibility and exhibits sustained antibacterial / biofilm and anti-inflammatory (M2 polarization promotion) effects against Staphylococcus aureus and Escherichia coli, while improving the compressive mechanical properties of the scaffold. The material is suitable for an anti-infection functional scaffold platform for implant-related infection prevention scenarios.

[0058] (4) The antibacterial and anti-inflammatory multifunctional composite material scaffold prepared by the invention has good biocompatibility and clinical application potential: the whole scaffold can be gradually degraded into non-toxic small molecules in vivo, avoiding long-term retention of metal particles. The high atomic number of Bi also endows the scaffold with CT visualization characteristics, providing a technical basis for postoperative image tracking and re-implantation positioning. The material system is suitable for various implantation scenarios such as orthopedics, dentistry and soft tissue repair (tissue regeneration), providing a safe, effective and imageable new solution for implant infection prevention.

[0059] (5) The invention realizes the transformation of the material from "passive compounding" to "functional coordination integration" through interface level integration design, specifically: 1) self-regulating ion release mechanism: the PDA shell as a dynamic interface adjustment layer stabilizes Bi 3+Ion release rate, avoiding initial burst release, achieving sustained antibacterial effect. 2) Interface coupling and mechanical enhancement: PDA surface rich -OH / -NH functional groups form a hydrogen bond network with PCL, significantly improving filler dispersion and stress transfer efficiency, making the scaffold have high strength and flexibility. 3) Multi-dimensional synergistic anti-inflammatory mechanism: Bi 3+ Ion inhibits bacterial toxin-induced inflammation, PDA phenolic hydroxyl / quinone pair system removes ROS, and the double pathways maintain immune homeostasis and promote M2 macrophage polarization. Through the above design, the invention realizes the spatiotemporal coupling effect of antibacterial-anti-inflammatory, while maintaining the mechanical stability of the scaffold, effectively prolonging the antibacterial period and significantly reducing the inflammatory response. In addition, the particle interface synergistic engineering strategy has universality and expandability, which can be extended to other metal-polymer systems, providing a new material design paradigm for anti-infective regenerative medicine. BRIEF DESCRIPTION OF DRAWINGS

[0060] Figure 1 is the preparation flow chart of the Bi / PDA-PCL scaffold of the present application.

[0061] Figure 2 is the TEM and SEM images of Bi and Bi / PDA particles; wherein, A is the TEM image of Bi; B is the TEM image of Bi / PDA; C is the SEM image of Bi; D is the SEM image of Bi / PDA.

[0062] Figure 3 is the energy dispersive X-ray spectrum (EDS) of Bi and Bi / PDA particles.

[0063] Figure 4 is the X-ray diffraction pattern of Bi and Bi / PDA particles.

[0064] Figure 5 is the infrared spectrum of Bi and Bi / PDA particles.

[0065] Figure 6 is the particle size and Zeta potential diagram of Bi and Bi / PDA particles.

[0066] Figure 7 is the thermogravimetric analysis diagram of Bi / PDA particles.

[0067] Figure 8 is the physical diagram of Bi / PDA-PCL scaffold (different Bi content).

[0068] Figure 9 is the SEM image of Bi / PDA-PCL scaffold.

[0069] Figure 10 is the XRD pattern of Bi / PDA-PCL scaffold.

[0070] Figure 11 is the infrared spectrum of Bi / PDA-PCL scaffold.

[0071] Figure 12 is the water contact angle spectrum of Bi / PDA-PCL scaffold.

[0072] Figure 13 is the Bi content of Bi / PDA-PCL scaffold. 3+ is the ion release curve.

[0073] Figure 14 is the compressive strength test result of Bi / PDA-PCL scaffold.

[0074] Figure 15 is the cell compatibility test result of Bi / PDA-PCL scaffold.

[0075] Figure 16 is the anti-inflammatory ability evaluation result of Bi / PDA-PCL scaffold on cells; wherein, A is the TNF-α expression level; B is the IL-6 expression level; C is the IL-10 expression level; D is the NO level.

[0076] Figure 17 is the anti-oxidation ability evaluation result of Bi / PDA-PCL scaffold on cells; wherein, A is the malondialdehyde (MDA) detection result; B is the glutathione (GSH) detection result.

[0077] Figure 18 is the quantitative evaluation result of Bi / PDA-PCL scaffold on the ability of regulating macrophage polarization; wherein, A is the statistical result of Bi / PDA-PCL scaffold stimulating M1 type macrophage (CD86 + ) polarization; B is the statistical result of Bi / PDA-PCL scaffold stimulating M2 type macrophage (CD206 + ) polarization.

[0078] Figure 19 is the experimental result of Bi / PDA-PCL scaffold on the ability of regulating M1 type macrophage polarization.

[0079] Figure 20 is the experimental result of Bi / PDA-PCL scaffold on the ability of regulating M2 type macrophage polarization.

[0080] Figure 21 is the bacteriostatic ability evaluation result of Bi / PDA-PCL scaffold on bacteria; wherein, A is the plate spectrum representing the bacterial content in the bacterial solution after different scaffold treatments by plate bacterial counting method; B is the quantitative analysis result of bacterial content.

[0081] Figure 22are the results of the evaluation of the ability of the Bi / PDA-PCL scaffold to inhibit the formation of bacterial biofilm; wherein A is a representative picture of crystal violet; and B is a quantitative evaluation of the absorbance of crystal violet. DETAILED DESCRIPTION

[0082] The application will be further described in conjunction with the following examples, but the embodiments of the application are not limited thereto.

[0083] In the following examples, the Bi particles were obtained by the following method: 4.8140 g of bismuth nitrate pentahydrate and 66 g of ethylene glycol were weighed into a three-way beaker, and then the mixture was vacuumed by nitrogen gas, and then transferred to a stainless steel hydrothermal reactor with a tetrafluoroethylene lining under a nitrogen atmosphere. After sealing, the reactor was reacted at 200 ℃ for 6 h. After the reaction was completed, the reactor was taken out and naturally cooled to room temperature, and then the cover was opened and the product was taken out. The product was washed twice with a mixed solution of deionized water and ethanol at a ratio of 1:1 (by volume) to obtain a pre-product, and then the precipitate was collected by centrifugation and dried at 60 ℃ under normal pressure to obtain Bi particles.

[0084] In the following examples, the Bi / PDA particles were obtained by the following method: 50 mg of Bi particles and 100 ml of PBS buffer were weighed, and then uniformly mixed by ultrasonic mixing at room temperature for 5-10 min and vacuumed by nitrogen gas (blown by nitrogen for 10 min to remove dissolved oxygen). At the same time, 10 mg of dopamine monomer was poured in. After stirring at 750 rpm and room temperature for 1 h, the precipitate was collected by centrifugation at 11000 rpm and room temperature, and then washed twice with a mixed solution of deionized water and ethanol at a ratio of 1:1 (by volume). The obtained precipitate was dried at 60 ℃ under normal pressure to obtain Bi / PDA particles.

[0085] In the following examples, the Bi / PDA-PCL material was obtained by the following method: 315 mg of poly-caprolactone (PCL) with Mn≈2 kDa, 585 mg of PCL with Mn≈80 kDa and 100 mg of Bi / PDA particles were weighed, dissolved in 5 ml of tetrahydrofuran (THF), and then stirred at 750 rpm and room temperature for 2-4 h. After mixing, the mixture was poured into a mold and dried at 60 ℃.

[0086] Other raw materials, reagents, equipment or processing techniques not specifically mentioned are conventional commercially available raw materials, reagents, equipment or conventional operations in the art.

[0087] Example 1 In this example, a Bi / PDA-PCL scaffold was prepared by loading 10% of Bi / PDA particles in PCL material. Figure 1), the specific steps are as follows: (1) Material ratio: 10% of Bi / PDA particles by mass percentage and 90% of PCL precursor (composed of PCL with molecular weight 2000:80000 at a mass ratio of 3.5:6.5) by mass percentage; (2) Preparation of Bi / PDA-PCL material: dissolve PCL with THF, then add Bi / PDA particles, mix PCL material and Bi / PDA particles with a magnetic stirrer, and vacuum dry residual THF at 60°C; (3) Preparation of 3D printed Bi / PDA-PCL scaffold: Use an extrusion type 3D printer to 3D print the Bi / PDA-PCL material, the process is: spray 75% alcohol and ultraviolet light sterilization inside the printer, add Bi / PDA-PCL material to the sterile printer cartridge, use a printing needle with a diameter of 0.4 mm for printing, and use the built-in temperature control system of the printer to control the cartridge temperature at 70°C. After the temperature is stable, adjust the extrusion air pressure to 400 kPa, observe that the cartridge out of the wire is continuous, complete the printing according to the designed printing path, and the printing path uses a single oblique filling method with a filling angle of 45°. To ensure the forming precision, the outer boundary uses 1-2 circle edge, the filling rate is 70%, the line width is 0.4 mm, and the layer thickness is 0.1 mm. The Bi / PDA-PCL scaffold (10% Bi / PDA) is printed.

[0088] Example 2 According to the method in Example 1, except that the mass ratio of Bi / PDA particles is different, which is 5 wt%, and the remaining steps are the same, the 3D printed Bi / PDA-PCL scaffold is recorded as 5% Bi / PDA.

[0089] Example 3 According to the method in Example 1, except that the mass ratio of Bi / PDA particles is different, which is 1 wt%, and the remaining steps are the same, the 3D printed Bi / PDA-PCL scaffold is recorded as 1% Bi / PDA.

[0090] Comparative Example 1 According to the method in Example 1, except that the introduction of PDA is omitted (Bi particles with the same Bi content as in the 10% Bi / PDA scaffold are directly mixed with PCL, and the scaffold is obtained by 3D printing), and the remaining steps are the same. The 3D printed scaffold is recorded as Bi-PCL.

[0091] Comparative Example 2 The procedure in Example 1 was followed, except that the addition of Bi / PDA particles was omitted, and the remaining steps were the same, and the 3D-printed scaffold was noted as PCL.

[0092] Effect Example 1: Structural characterization and performance testing of materials and scaffolds 1. Structural characterization To verify the formation of Bi / PDA fillers and their dispersion and interfacial bonding characteristics in the scaffolds, structural characterization was performed on the obtained Bi / PDA particles and scaffolds (10% Bi / PDA, 5% Bi / PDA, 1% Bi / PDA, Bi-PCL, PCL).

[0093] (1) Microscopic morphology analysis: To observe the microscopic structure characteristics of Bi / PDA particles and their Bi / PDA-PCL scaffolds, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used for morphology analysis. TEM was used to characterize the particle size, dispersity, and coating layer morphology of Bi / PDA particles. The sample was ultrasonically dispersed in ethanol, then dropped onto a copper mesh and naturally dried. SEM was used to observe the surface and cross-sectional microstructure of the scaffold. The sample was treated with gold spraying and tested under high vacuum conditions. The acceleration voltage for testing was 5-10 kV, and the magnification was adjusted according to the observation requirements. The obtained images were used to analyze the Bi / PDA coating structure and its distribution and interlayer structure characteristics in the PCL scaffold.

[0094] TEM and SEM images of Bi / PDA particles and Bi particles are shown in Figure 2 As can be seen from the SEM images, Bi particles are almost spherical in shape, with a smooth surface and slight aggregation. Bi / PDA particles are also spherical, but the surface is rougher. TEM images further illustrate the particle surface and core-shell structure: Bi particles are compact, smooth, and nearly spherical in shape, while Bi / PDA particles have a relatively dark metal core surrounded by a lighter PDA shell, which makes the particle surface relatively rough.

[0095] Actual images and SEM images of the scaffolds are shown in Figure 8 and Figure 9 As can be seen, the color of the scaffold gradually darkens with increasing Bi content Figure 8 ). SEM images show that all scaffolds have similar smooth morphology on the surface, with no obvious surface pores, which may be attributed to the effect of the mixed molecular weight of polycaprolactone (PCL), which can promote the wetting and interlayer fusion of the filaments Figure 9 ).

[0096] (2) Energy-dispersive X-ray spectroscopy (EDS) analysis: Elemental analysis of Bi / PDA particles was performed using EDS. The samples were sputter-coated with gold and observed under high vacuum. Detected elements included Bi, C, O, and N, used to confirm the presence of the PDA coating layer. Mapping was used to acquire the overall elemental distribution and local interfacial variations. The accelerating voltage was set to 10–15 kV, and the signal acquisition time was adjusted appropriately based on sample thickness and elemental signal intensity. The resulting energy dispersive spectroscopy (EDS) and elemental distribution maps were used to analyze the interfacial bonding characteristics of the Bi / PDA filler.

[0097] Bi / PDA particles and EDS of Bi particles, such as Figure 3 As shown in the figure, both curves show obvious Bi characteristic peaks (Bi Mα and Bi Lα), indicating that the PDA encapsulation did not introduce other elemental impurities.

[0098] (3) X-ray diffraction (XRD) analysis: To characterize the crystal structure of Bi / PDA particles and their Bi / PDA-PCL scaffolds, XRD analysis was employed. Test samples included Bi particles, Bi / PDA particles, and scaffolds with different ratios to compare the phase changes before and after coating and composite formation. Cu Kα rays (λ = 1.5406 Å) were used as the light source, with a scanning range of 20°–70° (2θ), a step interval of 0.02°, and a scanning rate of 4° / min. The resulting diffraction patterns were used to analyze the phase composition of the samples and the distribution of the Bi / PDA filler within the polymer matrix.

[0099] Bi / PDA particles and XRD patterns of Bi particles are shown below. Figure 4 As shown in the figure, the Bi sample is well-crystallized metallic Bi with typical hexagonal diffraction peaks, indicating that the PDA encapsulation does not change the metallic state of Bi. Furthermore, the peak intensity of Bi in the composite sample increases with the filler content: 1% < 5% < 10%, which is consistent with expectations.

[0100] XRD pattern of the stent Figure 10 As shown, the intensity of the diffraction peak of Bi increases with the increase of Bi / PDA content; at the same time, the intensity of the characteristic peak related to CO increases, confirming that Bi / PDA has been successfully incorporated into the scaffold.

[0101] (4) Fourier transform infrared spectroscopy (FTIR) analysis: FTIR analysis was performed to characterize the Bi / PDA particles and their chemical structure in the PCL matrix. The test samples included Bi particles, Bi / PDA particles, and scaffold materials with different ratios, to compare changes in characteristic absorption before and after coating and after composite formation. The KBr pellet method was used for testing at 4000–400 cm⁻¹. -1Scanning within the wavenumber range with a resolution of 4 cm. -1 The obtained spectra were used to identify the characteristic peaks of the main functional groups in the sample, including hydroxyl (–OH), amino (–NH), carbonyl (C=O), and ether bonds (C–O–C), to confirm the interaction between the PDA coating and the filler and the polymer matrix.

[0102] Infrared images of Bi / PDA particles are shown below. Figure 5 As shown in the figure: the spectrum of the Bi / PDA sample at 3400 cm⁻¹ is visible. -1 A broad absorption band appears on both sides, which can be attributed to the OH / NH stretching vibration, indicating that PDA brings abundant hydroxyl and amino groups; in the 2930-2850 cm⁻¹ range... -1 A distinct absorption peak appears at 1600 cm⁻¹, corresponding to the CH stretching vibration; at 1600 cm⁻¹... -1 The presence of characteristic absorption bands nearby, attributed to aromatic C=C stretching vibrations, confirms the presence of catechol and indole / benzene ring structures of PDA in Bi / PDA. In contrast, the Bi sample's spectrum is only at 1630 cm⁻¹. -1 Weak absorption is observed in the region (corresponding to the bending vibration of OH groups in adsorbed water), at 1400-1000 cm⁻¹. -1 A weak CH bending vibration peak was observed in the region. These spectral differences confirm that PDA has been successfully coated on the surface of Bi particles.

[0103] Infrared image of the bracket as follows Figure 11 As shown in the figure: Significant differences exist in the Fourier transform infrared spectra of Bi-PCL and Bi / PDA-PCL scaffolds. Compared to Bi-PCL, the spectra of 1%, 5%, and 10% Bi / PDA-PCL are in the 3200-3500 cm⁻¹ range. -1 A broad OH / NH absorption band appears at 1600 cm⁻¹. -1 New absorption peaks appear on the left and right (corresponding to aromatic C=C / C=N stretching vibrations), at 1510 cm⁻¹. -1 The presence of shoulder peaks nearby (corresponding to NH bending vibration / CN stretching vibration) confirms successful PDA incorporation into the scaffold. Furthermore, all samples retained the characteristic absorption peaks of polycaprolactone (2945 / 2865 cm⁻¹). -1 The vibration is CH2 stretching vibration at 1720 cm. -1 The vibrations at C=O are at 1240 and 1160 cm. -1 (This is a COC stretching vibration).

[0104] 2. Material Characterization (1) Analysis of particle size and Zeta voltage: To characterize the particle size distribution and dispersion state of Bi / PDA particles, dynamic light scattering (DLS) method was used for particle size test. A small amount of Bi / PDA particles were dispersed in deionized water and treated by ultrasonic for 5-10 min to obtain a uniform suspension. The test was carried out at room temperature, the wavelength of incident light was 633 nm, and the scattering angle was 90°. The obtained particle size distribution graph was used to analyze the average hydration diameter and distribution uniformity of the particles. To determine the surface charge characteristics and dispersion stability of Bi / PDA particles, Zeta potential analysis method was used for characterization. The test sample was Bi / PDA particle suspension dispersed in deionized water or PBS buffer, which was placed in a disposable sample cell for detection after ultrasonic dispersion. The test temperature was kept at 25°C, and the pH was about 7.0. Each sample was measured three times and the average value was taken to ensure the accuracy of the data. The measured Zeta potential was used to evaluate the surface charge properties of the particles and the colloidal stability in water medium.

[0105] The particle size and voltage diagram of Bi / PDA particles are shown in Figure 6 From the figure, it can be seen that the average particle size of Bi sample is 222.07 ± 63.3 nm, while the average particle size of Bi / PDA sample increases significantly to 354.67 ± 38.37 nm, indicating that PDA is successfully coated on the surface of Bi; the Zeta potential of Bi sample is -0.72 ± 0.58 mV, while the Zeta potential of Bi / PDA sample becomes significantly negative, decreasing to -3.04 ± 0.09 mV, indicating that after PDA coating, the particle surface has more negative charges, which improves the dispersion stability.

[0106] (2) Thermogravimetric (TGA) analysis: To study the thermal stability and component content of Bi / PDA particles, TGA was used for testing. The test sample was Bi / PDA particles. The experiment was carried out in nitrogen atmosphere, and the gas flow rate was set to 40-60 mL / min to avoid oxidation interference. The heating rate was 10 ℃ / min, and the temperature range was room temperature to 800 ℃. The obtained thermogravimetric (TG) and derivative thermogravimetric (DTG) curves were used to analyze the decomposition temperature, residual rate and organic component content change of the sample, so as to evaluate the PDA coating ratio. Each sample was measured three times and the average value was taken.

[0107] The thermogravimetric analysis diagram of Bi / PDA particles is shown in Figure 7 From the figure, it can be seen that there is a significant mass loss between 200°C and 400°C, which is mainly caused by the decomposition of PDA and other organic components; above 400°C, the mass loss tends to be stable, indicating that the inorganic part of the composite (Bi) has high thermal stability. It shows that Bi / PDA can maintain good thermal stability, and 89.75 ± 1.2% of Bi particles are coated.

[0108] (3) Water contact angle test (WCA): To evaluate the wettability of the scaffold surface, static water contact angle (WCA) test was used to determine the surface hydrophilicity of scaffolds in different groups. The test samples included scaffolds obtained from Examples 1-3 and Comparative Examples 1-2, and the test was carried out at room temperature using deionized water as the contact medium. A fixed volume of water droplet (about 5 μL) was dropped on the surface of the sample each time, and the contact angle measuring instrument was used to automatically capture the droplet profile and calculate the static contact angle value. Three different positions of each sample were selected for parallel testing and the average value was taken to ensure the representativeness of the data. The contact angle obtained by the test was used to analyze the effect of Bi / PDA filler content on the wettability of the scaffold surface.

[0109] The water contact angle of the scaffold is shown in Figure 12 : the water contact angle of pure PCL is 74.26±12.36°, the hydrophilicity of Bi-PCL is similar to that of the pure PCL group, and with the increase of Bi / PDA content, the water contact angle decreases, and the water contact angle of the 10% Bi / PDA scaffold decreases to 43.85±9.12°, which is consistent with the effect of PDA-mediated surface hydrophilization, indicating that Bi / PDA filler is more helpful than Bi filler in improving the hydrophilicity of PCL scaffold.

[0110] (4) Ion release curve analysis: To study the Bi 3+ ion release behavior of Bi / PDA filler in the scaffold, inductively coupled plasma mass spectrometry (ICP-MS) was used for quantitative analysis. A certain mass of scaffold sample was placed in a centrifuge tube containing a predetermined volume of phosphate buffered solution (PBS, pH 7.4, the ratio of scaffold mass to solution volume was 1 g:100 ml), and incubated at 37 ℃ constant temperature oscillation. A fixed volume of soaking solution was taken out at set time points (such as 1 h, 24 h, 72 h, 7 d, etc.), and an equal volume of fresh PBS was added to maintain the constant total volume. The collected soaking solution was acidified by concentrated nitric acid (HNO3, 15 mol / L) (the volume of nitric acid accounted for one thousandth of the total liquid volume) for metal ion concentration determination. The change of Bi 3+ concentration with time was used to draw the cumulative release curve to analyze the ion release rule of the material. Each sample was measured three times and the average value was taken.

[0111] The Bi 3+ ion release curve of the scaffold is shown in Figure 13 : it can be seen from the figure that the Bi-PCL scaffold has a significant Bi burst release within the first 24 h. Due to the regulation of PDA shell layer, the cumulative release amount of Bi in Bi / PDA-PCL scaffold shows a slow and continuous rising trend within 7 days. In addition, at each time point, the Bi3+ The release amount increases with the increase of Bi / PDA content. This shows that the wrapping of PDA on Bi helps to control the release of Bi, prolongs the effective antibacterial time of Bi. 3+ 3+

[0112] (5) Compression performance test: The compression performance of the obtained scaffold samples was tested by using a universal mechanical testing machine. The sample was placed between the test fixtures, and axial compression was performed according to the loading rate of 0.5 mm·min -1 The load and displacement data were recorded and converted into stress-strain relationship. The compression modulus of the scaffold was calculated according to the slope of the initial linear segment of the stress-strain curve, and the stress value at the strain of 10% was taken as the compression strength. Each sample was repeatedly measured three times and the average value was taken.

[0113] The evaluation results of the compression strength of the scaffold are shown in Table 2: Figure 14 The test results show that the compression strength of the scaffold gradually increases with the increase of the Bi / PDA filler content, which shows that the introduction of Bi / PDA can effectively enhance the overall bearing capacity and structural stability of the scaffold. Among them, the compression strength of the 10% Bi / PDA scaffold is the highest, showing excellent anti-deformation performance; while the Bi-PCL scaffold without PDA coating has relatively low compression strength, showing insufficient interface bonding and poor stress transmission efficiency. The results show that the PDA coating layer plays a key role in improving the compatibility of the filler and the PCL matrix, so that the load stress is more evenly distributed in the material, thereby having better compression performance than the pure PCL scaffold.

[0114] Example 2: Biological function verification of the scaffold: 1. Cell compatibility evaluation of the scaffold To verify the biological safety and adaptability of the above-mentioned scaffold to cell growth, the cell compatibility of the scaffold prepared in the application was evaluated to determine whether the material has potential toxicity to cells. The experimental design includes a blank control group (cells not contacting the scaffold, used to reflect the activity baseline of the cells under normal culture conditions) and different scaffold proportion groups (adding the scaffold samples obtained in Examples 1-3 and Comparative Examples 1-2 under cell culture conditions, respectively, to evaluate the influence of the scaffold on cell activity and toxicity). The blank control group is used as a baseline reference to compare the relative cell activity of each scaffold group; different scaffold proportion groups are used to observe the biological safety of the material at different proportions. The specific steps are as follows: ​​The above stents were prepared into cylindrical stents with a diameter of 5 mm and a height of 1 mm, 1 stent per well, 3 stents per group, and were sterilized by ultraviolet radiation for half an hour, then immersed in 75% ethanol solution for 12 hours, then washed with PBS for 3 times, and 500 μL of RAW264.7 cell suspension (3×10 5 cells were inoculated per well) was added dropwise, then 0.5 mL of DMEM complete medium was added per well, and it was cultured at 37°C and 5% CO2. After 3 days of culture, the stents in each group were transferred to a new 24-well plate, washed with PBS for 3 times, and the CCK-8 detection kit was used to evaluate the cell proliferation ability. This method is based on the colorimetric reaction of cell metabolites, and the absorbance of the solution reflects the cell survival and proliferation state, thereby indirectly evaluating the cell compatibility of the material. Each group of experiments was performed in triplicate and the average value was used for subsequent statistical analysis.

[0115] The cell compatibility of the stents is shown in Figure 15 Figure, it can be seen that there is no significant difference in cell viability between all stent groups and the control group, indicating that all stents have good cell compatibility.

[0116] 2. Evaluation of the anti-inflammatory performance of the stents To verify the regulatory effect of the stent material under inflammatory conditions, the in vitro anti-inflammatory performance was evaluated using a cell inflammation model induced by lipopolysaccharide (LPS). The experiment set up a blank control group (cells without LPS and stents, as a negative control under normal conditions), an LPS group (cells stimulated only by LPS, used to establish a pro-inflammatory model), and different stent ratio groups (stent samples obtained from Examples 1-3 and Comparative Examples 1-2 were added under LPS stimulation conditions, used to evaluate the regulatory ability of the stent material on the inflammatory response). The specific steps are as follows: RAW264.7 cells were first plated in a 24-well plate at 5×10 4 cells per well, and after being stimulated by 1 μg / ml LPS overnight, different groups of stents were added, each with a diameter of 5 mm and a height of 1 mm, 1 stent per well, and 3 stents per group. After the cells contacted the stents for 72 hours, the cells and their supernatants in the culture system were detected. The expression levels of inflammatory-related factors (such as TNF-α, IL-6, IL-10, NO) were measured to evaluate the inflammatory state of each group. The detection method uses conventional means in the art, including but not limited to enzyme-linked immunosorbent assay (ELISA) to quantitatively analyze the differences in inflammatory factors under different treatment conditions. Each group of experiments was performed in triplicate and the average value was used for subsequent statistical analysis.

[0117] The results of the evaluation of the anti-inflammatory ability of the stents on cells are shown in Figure 16As shown, the detection results of pro-inflammatory factors TNF-α, IL-6, NO, and anti-inflammatory factor IL-10 indicate that while the Bi-PCL group can reduce the levels of pro-inflammatory factors to some extent, the effect is limited. In contrast, the Bi / PDA-PCL scaffold of this invention has a more significant inhibitory effect on TNF-α, IL-6, and NO, and a significantly enhanced promoting effect on IL-10, showing a trend of increasing with increasing Bi / PDA content. Among them, the 10% Bi / PDA group performed best, with the largest decrease in pro-inflammatory factors and the most significant increase in IL-10. This indicates that although Bi-PCL has a certain anti-inflammatory ability, Bi / PDA, as a scaffold filler, can simultaneously exert the anti-inflammatory properties of Bi and PDA, achieving a better anti-inflammatory effect.

[0118] 3. Evaluation of the antioxidant capacity of the stent To verify the antioxidant capacity of the scaffold under oxidative stress, an LPS-induced cellular oxidative stress model was used for in vitro evaluation. The experiment included a blank control group (cells without LPS or the scaffold, reflecting normal oxidative state), an LPS group (cells stimulated only with LPS, used to establish an oxidative stress model), and groups with different scaffold ratios (scaffold samples from Examples 1–3 and Comparative Examples 1–2 were added under LPS stimulation conditions to assess the antioxidant regulatory effect of the scaffold). In vitro antioxidant assessment was performed 72 hours after LPS-stimulated macrophages were exposed to the scaffold. The LPS stimulation method, concentration, and time were the same as in step “2. Evaluation of the Anti-inflammatory Performance of the Scaffold” above. Oxidative stress-related indicators in the cells and their culture supernatant were detected, including malondialdehyde (MDA) concentration (reflecting cellular lipid peroxidation levels) and reduced glutathione (GSH) content (assessing cellular antioxidant capacity). Each experiment was performed in triplicate, and the average value was used for subsequent statistical analysis.

[0119] Assessing the antioxidant capacity of scaffolds for cells, such as Figure 17 As shown: by Figure 17 As can be seen from A in the text, while the Bi-PCL scaffold can reduce MDA levels to some extent, the effect is limited; however, the Bi / PDA-PCL scaffold of this invention, especially the 10% Bi / PDA group, can significantly reduce MDA content and significantly alleviate oxidative damage. Figure 17 As can be seen from B, the increase in GSH level in the Bi-PCL group was relatively small, while the GSH level in the Bi / PDA-PCL group gradually increased with the increase of Bi / PDA content, with the 10% Bi / PDA group reaching the highest value, showing the strongest antioxidant capacity.

[0120] 4. Evaluation of the regulation of macrophage polarization capacity by scaffolds To verify the regulation of the scaffold on macrophage polarization in an inflammatory environment, an in vitro macrophage model induced by LPS was used for quantitative evaluation, and the stimulation method was the same as the above step "2. Anti-inflammatory performance evaluation of the scaffold". The experiment set up a blank control group (macrophages without LPS or scaffold, used to reflect the normal polarization state), an LPS group (macrophages stimulated only by LPS, used to establish an inflammatory cell model), and different scaffold ratio groups (macrophages were added with the scaffold samples obtained in Examples 1-3 and Comparative Examples 1-2 under the condition of LPS stimulation, used to evaluate the influence of the scaffold on the polarization behavior). After the culture ended, flow cytometry was used to detect the macrophages in each group, PE-F4 / 80 antibody was used to label the macrophage population, and the positive cell proportion of APC-CD86 (M1 type marker) and APC-CD206 (M2 type marker) was jointly detected, so as to quantitatively analyze the polarization state under different treatment conditions. The flow cytometry detection results were used to show the distribution of CD86 and CD206 positive cells in each group, and statistical analysis was carried out combined with the positive proportion. Each group of experiments was determined in triplicate and the average value was taken.

[0121] The results are shown in Table 1. Figures 18-20 Figure 18 The results of quantitative evaluation of the ability of the scaffold material to regulate macrophage polarization by flow cytometry are shown in Table 1. The detection results show that with the increase of Bi / PDA content, the proportion of M1 type (CD86 + ) macrophages gradually decreases, and the proportion of M2 type (CD206 + ) macrophages gradually increases, indicating that the scaffold can effectively inhibit the inflammatory phenotype and promote the transformation of the repair phenotype. Among them, the 10% Bi / PDA group performs best, and its ability to inhibit M1 type and promote M2 type polarization is significantly higher than that of the Bi-PCL scaffold without PDA coating at the same Bi content. Therefore, the Bi / PDA-PCL scaffold of the present application shows stronger immunoregulation and anti-inflammatory performance under the same Bi content, and can realize the stabilization of the inflammatory microenvironment and the promotion of tissue repair by adjusting the polarization direction of macrophages.

[0122] Figure 19 is the ability of the scaffold to regulate M1 polarization of macrophages, and the flow cytometry of RAW264.7 cells treated with different scaffolds is shown in the figure. Compared with other groups, the proportion of CD86 + macrophages (M1 phenotype, pro-inflammatory type) in the 10% Bi / PDA scaffold group is the lowest, which inhibits the polarization of macrophages to M1 phenotype, indicating that PDA coating has anti-inflammatory regulation effect, and the 10% Bi / PDA scaffold has the best anti-inflammatory effect.

[0123] Figure 20 ​is the ability of the scaffold to regulate the M2 polarization of macrophages, and the figure is the flow chart of RAW264.7 cells treated by different scaffolds stained by APC-CD206 and PE-F4 / 80. Compared with other groups, the CD206 + The proportion of macrophages (M2 phenotype, anti-inflammatory type) is the highest, and the promotion of macrophages to M2 phenotype indicates that PDA coating has an anti-inflammatory regulatory effect, and 10% Bi / PDA scaffold has the best anti-inflammatory effect.

[0124] 5. Evaluation of the antibacterial ability of the scaffold To verify the antibacterial performance of the scaffold material, the bacteriostatic effect was evaluated by using an in vitro bacterial culture model. The experiment set up a blank control group (bacterial culture system without adding scaffolds) and different scaffold groups (adding samples obtained from Examples 1-3 and Comparative Examples 1-2) for comparison of the influence of the material on bacterial growth. The experimental bacterial strains were S. aureus GDMCC1.1220 and E. coli GDMCC1.1917 purchased from Guangdong Microbial Culture Collection Center as representative pathogenic strains. The specific steps are as follows: The two bacteria were inoculated in LB medium and cultured at 37 ℃, 180 rpm for 12 hours until the logarithmic growth phase (OD 600 ≈ 0.6), and then diluted to 10 6 CFU / mL for the experiment. The 5mm in diameter and 1mm in height scaffolds were added to 3ml bacterial solution and cultured at 37℃, 180rpm for 72 hours for evaluation of the influence of the scaffold on bacterial growth and biofilm formation. The bacterial proliferation was determined by dilution plating method to determine the colony forming units (CFU), and the antibacterial rate was calculated; the biofilm formation ability was evaluated by crystal violet staining for 20 minutes, then washed twice with PBS to elute the unbound crystal violet dye, then 1ml ethanol was used to elute the bound crystal violet dye, and the absorbance (OD 570 nm) was measured at 570nm to quantitatively evaluate the inhibitory effect of the scaffold on biofilm growth. Each group of samples was tested in triplicate, and the average value was used for subsequent statistical analysis.

[0125] The results of the evaluation of the antibacterial ability of the scaffold on bacteria are shown in Table 2. Figure 21As shown in the figure, the higher the Bi / PDA content, the stronger the inhibition of S. aureus and E. coli, showing obvious concentration-dependent bacteriostatic effect. The bacteriostatic rate of 10% Bi / PDA on the two kinds of bacteria is more than 85%, which has the most significant antibacterial effect. The bacteriostatic effect of Bi-PCL scaffold without PDA modification is only higher than 1%, which shows that Bi / PDA-PCL is significantly better than Bi-PCL in inhibiting the two kinds of bacteria at the same Bi content, and the wrapping of PDA prolongs the release of Bi 3+ The effective antibacterial duration is 3 days in vitro.

[0126] The results of evaluating the ability of the scaffold to inhibit the formation of bacterial biofilm are shown in the figure Figure 22 As shown in the figure, the higher the Bi / PDA content, the stronger the inhibition of S. aureus and E. coli, showing obvious concentration-dependent bacteriostatic effect. The bacteriostatic rate of 10% Bi / PDA on the two kinds of bacteria is more than 85%, which has the most significant antibacterial effect. The bacteriostatic effect of Bi-PCL scaffold without PDA modification is only higher than 1%, which shows that Bi / PDA-PCL is significantly better than Bi-PCL in inhibiting the two kinds of bacteria at the same Bi content, and the wrapping of PDA prolongs the release of Bi

[0127] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited by the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, which are all included in the protection scope of the present application.

Claims

1. A Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers, characterized in that, Comprise the following components by mass percentage: 1%~10% of Bi / PDA particles, 90%~99% of polycaprolactone; wherein, The polycaprolactone is obtained by mixing polycaprolactone with a number average molecular weight of 2 kDa and 80 kDa at a mass ratio of 2~4:6~8. 2.The Bi / PDA-PCL nanocomposite of claim 1, characterized in that: The amount of Bi / PDA particles is 5%~10% by mass percentage; The polycaprolactone is obtained by mixing polycaprolactone with a number average molecular weight of 2 kDa and 80 kDa at a mass ratio of 3~4:6~7. 3.The Bi / PDA-PCL nanocomposite of claim 2, characterized in that: The amount of Bi / PDA particles is 10% by mass percentage; The polycaprolactone is obtained by mixing polycaprolactone with a number average molecular weight of 2 kDa and 80 kDa at a mass ratio of 3.5:6.

5. 4.The Bi / PDA-PCL nanocomposite of claim 1, characterized in that: The Bi / PDA particles are prepared by the following method: Bi particles are added to a buffer solution, ultrasonically dispersed and mixed uniformly, and purged with nitrogen to remove dissolved oxygen, then dopamine monomer is added, stirred and reacted, then centrifuged and washed, and dried to obtain Bi / PDA particles; The mass ratio of Bi particles to dopamine monomer is 3~8:1; The buffer solution is a PBS buffer solution. 5.The Bi / PDA-PCL nanocomposite of claim 4, characterized in that: The Bi particles are prepared by the following method: Bi(NO3)3·5H2O is dissolved in ethylene glycol under nitrogen protection, a uniform colorless solution is formed and vacuumed, then the solution is placed in a sealed condition at 150~240 ℃ for reaction, after the reaction is completed, it is cooled to room temperature, washed and dried to obtain Bi particles; The mass ratio of Bi(NO3)3·5H2O to ethylene glycol is 1:10~15; The reaction time is 4~24 h.

6. Process for the preparation of Bi / PDA-PCL nanocomposites with Bi / PDA particles as fillers according to any one of claims 1 to 5, characterized in that, The following steps are included: polycaprolactone and Bi / PDA particles are dissolved in tetrahydrofuran, stirred and mixed uniformly, then poured into a mold, and dried in a ventilated condition to obtain Bi / PDA-PCL nanocomposite.

7. A 3D printing based Bi / PDA-PCL scaffold, characterized by: The Bi / PDA-PCL nanocomposite with Bi / PDA particles as fillers according to any one of claims 1~5 is obtained by 3D printing.

8. The 3D printing based Bi / PDA-PCL scaffold according to claim 7, characterized in that, The Bi / PDA-PCL nanocomposite is prepared by the following method: a 3D printer is used, the temperature of the printer's barrel is controlled at 60~90 ℃, the extrusion gas pressure is 200~600 kPa, the printer's barrel is observed to be continuous in shape, and 3D printing is completed according to the set printing path; The diameter of the printing needle of the 3D printer is 0.2~0.6 mm.

9. Use of the Bi / PDA-PCL nanocomposite of any one of claims 1-5 using Bi / PDA particles as fillers and / or the Bi / PDA-PCL scaffold based on 3D printing of any one of claims 7-8 for preparing an antibacterial, anti-inflammatory and / or tissue repair product.

10. The use of claim 9, wherein the bacteria include Staphylococcus aureus and Escherichia coli; and the product includes an in vitro antibacterial drug, an anti-inflammatory drug, or an implant scaffold for orthopedics, oral surgery and / or soft tissue repair. ​ ​

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