Preparation method and application of drug-loaded copper sulfide polyethylene glycol hydrogel composite poly-caprolactone stent

Abstract

The application relates to a preparation method and application of a drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone support. The preparation method comprises the following steps: mixing dexamethasone sodium phosphate Dexp, copper sulfide nanoparticles CuS NPs and a tris-hydroxymethyl aminomethane hydrochloride Tris-HCl solution with pH=8.5 under light-proof conditions to obtain drug-loaded copper sulfide nanoparticles D-CuS NPs; in a 1xPBS medium containing triethanolamine, the D-CuS NPs are doped into a four-arm-polyethylene glycol-mercapto polymer network for crosslinking to obtain drug-loaded copper sulfide polyethylene glycol D-CuS-PEG hydrogel; a polycaprolactone PCL support is obtained through 3D printing; the D-CuS-PEG hydrogel is coated on the surface of the PCL support through an immersion coating method, and the D-CuS-PEG hydrogel is completely gelled to obtain a drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone D-CuS-PEG-PCL support.

Description

Technical Field

[0001] This invention belongs to the field of biomaterial preparation technology, specifically relating to a method for preparing and applying a drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold. Background Technology

[0002] 3D-printed polycaprolactone (PCL) scaffolds possess excellent mechanical strength, good biocompatibility, and reliable stability, making them widely used in bone tissue engineering. They are a reliable medical material approved by the U.S. Food and Drug Administration (FDA). However, limitations such as insufficient biological function and poor hydrophilicity of PCL scaffolds restrict further functional improvements, ultimately leading to less than ideal implantation results.

[0003] In recent years, inspired by the concept of organoids, researchers have addressed these issues through various modification methods. These include biomineralization techniques, the introduction of bioactive micro / nanomaterials and functional polymers, and the fabrication of modified PCL active scaffolds to improve their physicochemical properties. However, the PCL active scaffolds obtained through these modification methods often suffer from limited functionality. To achieve efficient bone regeneration in mammalian fractures, combining 3D-printed PCL scaffolds with a multifunctional hydrogel-based soft-hard composite scaffold drug delivery system that integrates spatial mechanical support, controllable drug release, and photothermal ossification is an effective strategy. Summary of the Invention

[0004] To address the aforementioned problems, the present invention aims to provide a method for preparing a multifunctional drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold that can be applied to bone repair materials. This composite scaffold possesses excellent photothermal conversion, controlled drug release, antibacterial properties, biocompatibility, and osteogenic differentiation capacity. Furthermore, under the combined action of near-infrared light (NIR), its osteogenic differentiation capacity can be further enhanced.

[0005] Specifically, in the first aspect, the present invention provides a method for preparing a drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold, comprising the following steps:

[0006] Dexamethasone sodium phosphate (Dexp), copper sulfide nanoparticles (CuSNPs), and a Tris-HCl solution of tris(hydroxymethyl)aminomethane hydrochloride (pH=8.5) were mixed under light-protected conditions to obtain drug-loaded copper sulfide nanoparticles (D-CuSNPs).

[0007] In a 1×PBS medium containing triethanolamine, the D-CuSNPs were incorporated into a four-arm-polyethylene glycol-thiol 4arm-PEG-SH polymer network for crosslinking to obtain drug-loaded copper sulfide polyethylene glycol D-CuS-PEG hydrogel.

[0008] Polycaprolactone (PCL) scaffolds were obtained through 3D printing.

[0009] The D-CuS-PEG hydrogel was coated onto the surface of the polycaprolactone PCL scaffold using an impregnation coating method. After complete gelation, the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone D-CuS-PEG-PCL scaffold was obtained.

[0010] Preferably, the ratio of dexamethasone sodium phosphate, copper sulfide nanoparticles, and Tris-HCl solution is 0.125-2.5 mg: 50-500 μg: 1-4 mL, and the concentration of dexamethasone sodium phosphate is controlled to be 0.035-0.725 mg / mL.

[0011] Preferably, the concentration of triethanolamine in the 1×PBS medium is controlled to be 200-600 mM, the concentration of CuS NPs is controlled to be 50-250 μg / mL, and the concentration of 4arm-PEG-SH is controlled to be 100-200 mg / mL.

[0012] Preferably, the weight-average molecular weight (Mw) of the polycaprolactone raw material is 60,000-100,000.

[0013] Preferably, the temperature for complete gelation is 25-37°C, and the time is 0.6-6 hours.

[0014] Secondly, the present invention provides a drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold prepared according to the above preparation method.

[0015] Preferably, the porosity of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold is 30-60%.

[0016] Preferably, in the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone stent, based on a total stent mass of 100 wt%, the mass fraction of the drug-loaded copper sulfide polyethylene glycol hydrogel is 5-20 wt%, and the mass fraction of the polycaprolactone stent is 80-95 wt%.

[0017] Thirdly, the present invention provides an application of the above-mentioned drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold in bone repair materials.

[0018] Beneficial effects

[0019] The D-CuS-PEG-PCL scaffold prepared using the method of this invention is a soft-rigid composite material constructed based on the organoid concept. This composite scaffold exhibits excellent photothermal conversion, controlled drug release, antibacterial properties, biocompatibility, and osteogenic differentiation capacity. Furthermore, its osteogenic differentiation capacity can be further enhanced under the combined action of near-infrared light (NIR).

[0020] The preparation method provided by this invention uses simple equipment and requires little investment, which is conducive to the mass production of D-CuS-PEG-PCL scaffolds and has broad application prospects. Attached Figure Description

[0021] Figure 1 The image shows a SEM image of the D-CuS-PEG hydrogel prepared in step (2) of Example 1.

[0022] Figure 2 The image shows the D-CuS-PEG hydrogels with different CuS NPs concentrations prepared in step (2) of Example 2.

[0023] Figure 3 The rheological analysis test diagrams are shown for the D-CuS-PEG hydrogel prepared in step (2) of Example 3 and the control group PEG hydrogel.

[0024] Figure 4 The images show physical and SEM images of the PCL scaffolds (a,d,g,j), PEG-PCL scaffolds (b,e,h,k), and CuS-PEG-PCL scaffolds (c,f,i,l) prepared in Example 4.

[0025] Figure 5 This is a drug release curve of the D-CuS-PEG-PCL stent at different drug concentrations in Example 4. The left graph represents the non-illuminated group, and the right graph represents the illuminated group.

[0026] Figure 6 The images show the in vitro osteogenic differentiation effects of the PEG-PCL scaffold (blank control), D-CuS-PEG-PCL scaffold, and NIR+D-CuS-PEG-PCL scaffold prepared in Example 5.

[0027] Figure 7 Images showing the osteogenesis effects of PEG-PCL scaffold (blank control), CuS-PEG-PCL scaffold, NIR+CuS-PEG-PCL scaffold, D-CuS-PEG-PCL scaffold and NIR+D-CuS-PEG-PCL scaffold at 4 and 8 weeks in vivo. Detailed Implementation

[0028] The present invention will be further illustrated by the following embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the present invention.

[0029] Based on the concept of organoid soft and hard combination, this invention provides a multifunctional drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold for use in bone repair materials and its preparation method.

[0030] The following exemplarily illustrates the preparation method of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold of the present invention, which mainly includes the following steps.

[0031] (1) Preparation of drug-loaded copper sulfide nanoparticles. Dexamethasone sodium phosphate (Dexp), copper sulfide nanoparticles (CuSNPs), and a solution of tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) at pH 8.5 were uniformly mixed and reacted in a shaker at 25°C and 300 rpm for 12-60 h in the dark. The mixture was then filtered and dried to obtain the drug-loaded copper sulfide nanoparticles (D-CuSNPs).

[0032] In some embodiments, the ratio of dexamethasone sodium phosphate, copper sulfide nanoparticles, and Tris-HCl solution can be 0.125-2.5 mg: 50-500 μg: 1-4 mL, and the concentration of dexamethasone sodium phosphate can be controlled to be 0.035-0.725 mg / mL. Increasing the concentration of dexamethasone sodium phosphate can increase the drug loading; however, excessive concentration often leads to the aggregation of drug-loaded nanoparticles, thus affecting the drug loading effect. Simultaneously, the amount of Tris-HCl solution also affects the loading efficiency of the nanoparticles and drug. Excessive amount often leads to reduced loading efficiency; insufficient amount affects the effective diffusion of the nanoparticles and drug, also resulting in reduced loading efficiency.

[0033] (2) Preparation of drug-loaded copper sulfide polyethylene glycol hydrogel. In a phosphate buffered saline solution containing triethanolamine (TEA) and 1×PBS medium, the D-CuS NPs prepared in step (1) were incorporated into a four-arm-polyethylene glycol-thiol (4arm-PEG-SH) polymer network for crosslinking to prepare the drug-loaded copper sulfide polyethylene glycol (D-CuS-PEG) hydrogel.

[0034] In 1×PBS medium, the covalent bonding between the -SH terminus of 4arm-PEG-SH and the S terminus of D-CuS NPs is accelerated by the catalyst triethanolamine. In some embodiments, the concentration of triethanolamine in the 1×PBS medium can be controlled to be 200-600 mM, the concentration of CuS NPs to be 50-250 μg / mL, and the concentration of 4arm-PEG-SH to be 100-200 mg / mL.

[0035] In the preparation of the drug-loaded copper sulfide polyethylene glycol (D-CuS-PEG) hydrogel, the concentration of triethanolamine affects the gelation rate; too low a concentration results in a slow gelation rate, while too high a concentration can cause toxic side effects. The concentration of CuS NPs mainly affects the photothermal conversion capability of the composite PCL scaffold. To a certain extent, the concentration of CuS NPs is directly proportional to the photothermal conversion capability; too low a concentration prevents the required temperature from being reached in time, while too high a concentration makes it difficult to control the heating rate. The concentration of 4arm-PEG-SH also affects the gelation rate; too low a concentration leads to a slow gelation rate, while too high a concentration can cause toxic side effects.

[0036] (3) Preparation of polycaprolactone (PCL) scaffolds. 3D PCL scaffolds were fabricated in a 3D printer by fused deposition modeling: PCL raw material (weight average molecular weight Mw: 60,000-100,000) was melted in the printing area at 120°; the design pattern of 0° / 60° / 120° along the z-axis was printed using an injection needle (diameter: 0.4 mm); a cuboid model (5cm×5cm) with a porosity of 30-60% and a height of 3mm was made; a punch with a diameter of 3mm or 4mm was selected to prepare a cylindrical polycaprolactone (PCL) scaffold.

[0037] (4) Preparation of drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold. The D-CuS-PEG hydrogel prepared in step (2) is coated onto the surface of the polycaprolactone PCL scaffold prepared in step (3) by dip coating method. After complete gelation, the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone (D-CuS-PEG-PCL) scaffold is obtained.

[0038] The impregnation and coating process can be as follows: immerse the PCL scaffold in D-CuS-PEG hydrogel, then remove the PCL scaffold and place it in a cool place until the hydrogel completely gels, thus obtaining the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone D-CuS-PEG-PCL scaffold. The temperature for complete gelation can be 25-37℃, and the time can be 0.6-6 hours.

[0039] The incompletely gelled precursor solution was coated onto the PCL scaffold. Utilizing the amphiphilic properties of PEG, the surface hydrophobic properties of PCL could be effectively improved. The porosity of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold was 30-60%; based on a total scaffold mass of 100 wt%, the mass fraction of the drug-loaded copper sulfide polyethylene glycol hydrogel was 5-20 wt%, and the mass fraction of the polycaprolactone scaffold was 80-95 wt%.

[0040] The following examples further illustrate the present invention in detail. It should also be understood that the following examples are only for further explanation of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within the appropriate scope.

[0041] Example 1

[0042] (1) Preparation of drug-loaded copper sulfide nanoparticles. Dexamethasone sodium phosphate (Dexp), copper sulfide nanoparticles (CuSNPs), and a Tris-HCl solution at pH 8.5 were uniformly mixed; the mixture was reacted thoroughly in a shaker at 25°C and 300 rpm for 48 h in the dark, filtered, and dried to obtain the drug-loaded copper sulfide nanoparticles (D-CuS NPs). The ratio of dexamethasone sodium phosphate, copper sulfide nanoparticles, and Tris-HCl solution was 1.5 mg: 500 μg: 2 mL; the drug loading concentration was 0.035 mg / mL.

[0043] (2) Preparation of drug-loaded copper sulfide polyethylene glycol hydrogel. In a 1×PBS medium containing triethanolamine, the D-CuS NPs prepared in step (1) were incorporated into a four-arm-polyethylene glycol-thiol (4arm-PEG-SH) polymer network for crosslinking to prepare the drug-loaded copper sulfide polyethylene glycol (D-CuS-PEG) hydrogel. The concentration of triethanolamine in the 1×PBS medium was controlled at 400 mM, the concentration of CuS NPs at 150 μg / mL, and the concentration of 4arm-PEG-SH at 100 mg / mL.

[0044] (3) Preparation of polycaprolactone (PCL) scaffold. The 3D-PCL scaffold was fabricated in a 3D printer by fused deposition modeling: the PCL raw material (Mw: 80000) was melted in the printing area at 120°; the design pattern of 0° / 60° / 120° along the z-axis was printed through an injection needle (diameter: 0.4 mm); a cuboid model (5cm×5cm) with a porosity of 50% and a height of 3mm was made; a punch with a diameter of 3mm was selected to prepare a cylindrical polycaprolactone (PCL) scaffold.

[0045] (4) Preparation of drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold. The D-CuS-PEG hydrogel prepared in step (2) was coated onto the surface of the polycaprolactone PCL scaffold prepared in step (3) by dip-coating. After complete gelation, the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone (D-CuS-PEG-PCL) scaffold was obtained. The dip-coating process was as follows: the PCL scaffold was immersed in the D-CuS-PEG hydrogel, and then the PCL scaffold was removed and placed in a cool place to allow the hydrogel to completely gel, thus obtaining the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone D-CuS-PEG-PCL scaffold; the complete gelation temperature was 30℃ and the time was 1 hour.

[0046] The porosity of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone scaffold prepared in Example 1 was 50%; based on a total scaffold mass of 100 wt%, the mass fraction of the drug-loaded copper sulfide polyethylene glycol hydrogel was 5 wt%, and the mass fraction of the polycaprolactone scaffold was 95 wt%.

[0047] Figure 1 The image shows a SEM image of the D-CuS-PEG hydrogel prepared in step (2) of Example 1. As can be seen from the image, CuSNPs are uniformly dispersed in the hydrogel scaffold.

[0048] Example 2

[0049] This embodiment follows the preparation steps of Example 1. The main difference is that in step (2), the concentrations of CuS NPs are controlled to be 0 μg / mL (control group), 50 μg / mL, 150 μg / mL and 250 μg / mL.

[0050] Figure 2 Figure 1 shows the physical images of D-CuS-PEG hydrogels prepared in step (2) of Example 2 with different CuS NP concentrations. Figures 1, 2, 3, and 4 represent the D-CuS-PEG hydrogels prepared with CuS NP concentrations of 0 μg / mL, 50 μg / mL, 150 μg / mL, and 250 μg / mL, respectively. Figure a shows a tilted view; Figure b shows an inverted view. Through this example and... Figure 2 It can be seen that as the concentration of CuS NPs increases, the gelation time decreases continuously, indicating that the concentration of CuS NPs affects the gelation rate of hydrogels and is positively correlated with adhesion.

[0051] Example 3

[0052] This embodiment follows the preparation steps of Example 1. The main difference is that in step (2), the concentration of triethylamine in 1×PBS medium is controlled to be 200mM, 400mM and 600mM respectively.

[0053] Figure 3 The figures show the rheological analysis results of the D-CuS-PEG hydrogel prepared in step (2) of Example 3 and the control group PEG hydrogel. G' represents the storage modulus, also called the elastic modulus; G” represents the loss modulus. As can be seen from the figures, the gap between G' and G” in the D-CuS-PEG hydrogel is larger than that in the PEG hydrogel, indicating that the D-CuS-PEG hydrogel has superior viscoelasticity. The addition of D-CuS NPs shortens the hydrogel formation time and improves the viscoelasticity of the hydrogel. At the test endpoint, the D-CuS-PEG hydrogel exhibits stronger mechanical properties, indicating that the introduction of CuS NPs also increases the mechanical properties of the composite hydrogel.

[0054] Example 4

[0055] This embodiment follows the preparation steps of Example 1. The main difference is that the drug loading concentration in step (1) is low (0.035 mg / mL), medium (0.345 mg / mL), and high (0.725 mg / mL). Simultaneously, PCL scaffolds, PEG-PCL scaffolds, and CuS-PEG-PCL scaffolds were prepared.

[0056] Figure 4 The images show physical and SEM images of the PCL scaffolds (a,d,g,j), PEG-PCL scaffolds (b,e,h,k), and CuS-PEG-PCL scaffolds (c,f,i,l) prepared in Example 4. As can be seen from the images, the PEG-PCL scaffold is transparent, while the CuS-PEG-PCL scaffold is dark green. Furthermore, the SEM images show that the CuS-PEG-PCL scaffold has a denser structure than the PEG-PCL scaffold, indicating that the introduction of CuS NPs improves the crosslinking degree of the hydrogel.

[0057] Figure 5 The graphs show the drug release curves of the D-CuS-PEG-PCL stent at different drug concentrations in Example 4. The left graph represents the non-illuminated group, and the right graph represents the illuminated group. In the illuminated group, before sampling at each sampling point, the D-CuS-PEG-PCL stent was irradiated with a 1064nm laser to raise the temperature to 42°C and irradiate continuously for 10 minutes to promote drug release. As can be seen from the graphs, in both the illuminated and non-illuminated groups, the cumulative drug release of the D-CuS-PEG-PCL stent at different time points increased with increasing concentration.

[0058] Example 5

[0059] This embodiment refers to the preparation steps of Example 1. The main difference is that the D-CuS-PEG-PCL scaffolds prepared in step (4) are subjected to near-infrared light (NIR) treatment (NIR+D-CuS-PEG-PCL) and not subjected to near-infrared light (NIR) treatment (D-CuS-PEG-PCL).

[0060] Figure 6 The figures show the in vitro osteogenic differentiation effects of the PEG-PCL scaffold (blank control), D-CuS-PEG-PCL scaffold, and NIR+D-CuS-PEG-PCL scaffold prepared in Example 5. CoL-1 represents type I collagen, OCN represents osteocalcin, RUNX-2 represents osteogenic-specific transcription factor-2, and BMP-2 represents bone morphogenetic protein-2. As can be seen from the figures, the D-CuS-PEG-PCL scaffold exhibits better osteogenic differentiation than the blank control. Furthermore, the osteogenic differentiation capacity of the D-CuS-PEG-PCL scaffold is further enhanced after near-infrared (NIR) treatment, indicating that NIR treatment can promote mesenchymal stem cells to further enhance their osteogenic differentiation effect by increasing drug release and creating a local warm microenvironment.

[0061] Example 6

[0062] Following the preparation steps in Example 1, polyethylene glycol hydrogel composite polycaprolactone (PEG-PCL) scaffolds, copper sulfide polyethylene glycol hydrogel composite polycaprolactone (CuS-PEG-PCL) scaffolds, near-infrared irradiated copper sulfide polyethylene glycol hydrogel composite polycaprolactone (NIR+CuS-PEG-PCL) scaffolds, drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone (D-CuS-PEG-PCL) scaffolds, and near-infrared irradiated drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone (NIR+D-CuS-PEG-PCL) scaffolds were prepared and implanted into a rat bone defect model to evaluate the in vivo therapeutic effect.

[0063] Figure 7 Images show the osteogenic effects of PEG-PCL scaffolds (blank control), CuS-PEG-PCL scaffolds, NIR+CuS-PEG-PCL scaffolds, D-CuS-PEG-PCL scaffolds, and NIR+D-CuS-PEG-PCL scaffolds at 4 and 8 weeks in vivo. BV represents bone tissue volume, and TV represents total tissue volume. The images show that the D-CuS-PEG-PCL scaffold treated with NIR light exhibits the strongest osteogenic capacity, indicating that NIR treatment promotes bone regeneration by increasing drug release and creating a local warm microenvironment.

[0064] Although the present invention has been described in detail through the preferred embodiments above, it should be understood that the above description should not be considered as a limitation of the present invention. Various modifications and substitutions to the present invention will be apparent to those skilled in the art after reading the above description. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. A method for the preparation of drug loaded copper sulphide polyethylene glycol hydrogel composite poly-caprolactone scaffolds, characterized by, The preparation method comprises the following steps: Dexamethasone sodium phosphate Dexp, copper sulfide nanoparticles CuS NPs, and a Tris-HCl solution with a pH of 8.5 are mixed under light-proof conditions to obtain drug-loaded copper sulfide nanoparticles D-CuS NPs; The D-CuS NPs are incorporated into a 4arm-polyethylene glycol-mercapto 4arm-PEG-SH polymer network for cross-linking in a 1×PBS medium containing triethanolamine to obtain drug-loaded copper sulfide polyethylene glycol D-CuS-PEG hydrogel; A polycaprolactone PCL support is obtained through 3D printing; The D-CuS-PEG hydrogel is coated on the surface of the polycaprolactone PCL support through dip coating, and the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone D-CuS-PEG-PCL support is obtained after complete gelation.

2. The production method according to claim 1, characterized by, The dexamethasone sodium phosphate, copper sulfide nanoparticles, and Tris-HCl solution are used in a ratio of 0.125-2.5 mg: 50-500 μg: 1-4 mL, and the concentration of the dexamethasone sodium phosphate drug loading is controlled to be 0.035-0.725 mg / mL.

3. The production method according to claim 1 or 2, characterized by, The concentration of triethanolamine in the 1×PBS medium is controlled to be 200-600 mM, the concentration of CuS NPs is controlled to be 50-250 μg / mL, and the concentration of 4arm-PEG-SH is controlled to be 100-200 mg / mL.

4. The production method according to any one of claims 1 to 3, characterized by, The weight average molecular weight Mw of the polycaprolactone raw material is 60,000-100,000.

5. The production method according to any one of claims 1 to 4, characterized by, The temperature of the complete gelation is 25-37℃, and the time is 0.6-6 hours.

6. A drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone support obtained through the preparation method according to any one of claims 1-5.

7. The drug loaded copper sulphide polyethylene glycol hydrogel composite poly-caprolactone scaffold according to claim 6, wherein, The porosity of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone support is 30-60%.

8. The drug loaded copper sulphide polyethylene glycol hydrogel composite poly-caprolactone scaffold according to claim 6 or 7, wherein, In the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone support, the mass fraction of the drug-loaded copper sulfide polyethylene glycol hydrogel is 5-20 wt% based on 100 wt% of the total mass of the composite support, and the mass fraction of the polycaprolactone support is 80-95 wt%.

9. Use of the drug-loaded copper sulfide polyethylene glycol hydrogel composite polycaprolactone support according to any one of claims 6-8 in a bone repair material.

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