Poly-l-lactide-caprolactone composite material, preparation method and application thereof, and vascular stent

Abstract

The application belongs to the technical field of biomedical materials, and provides a poly-L-lactide-caprolactone composite material, a preparation method and application thereof, and a vascular stent.The composite material is prepared from poly-L-lactide-caprolactone (PLCL) and metal oxides (one or more of ferroferric oxide, magnesium oxide, zinc oxide and titanium dioxide). Compared with PLLA, the composite material has better strength and toughness; the metal oxides can improve the degradation rate of the polymer PLCL. Therefore, the composite material has excellent toughness, strength and degradation rate. Further, especially when the metal oxide is ferroferric oxide, the elongation at break and tensile strength of the obtained composite material are significantly improved; the in-vitro degradation rate is also significantly improved; and the composite material has excellent biocompatibility.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a poly (L-lactide)-caprolactone composite material, a preparation method and application thereof, and a vascular stent. Background Art

[0002] Traditional poly (L-lactide) (PLLA) vascular stents have insufficient bending resistance (elongation at break <5%), making them prone to fracture. PLLA also degrades over a period of 3-5 years, far exceeding the 6-12 month window required for endothelial repair. Existing technologies, using L-lactide and caprolactone as monomers to prepare poly (L-lactide-caprolactone) (PLCL) as vascular stents, effectively improve the toughness of PLLA stents, but this results in a significant reduction in strength and a degradation period of nearly 3 years.

[0003] Therefore, providing a vascular stent material that combines toughness, strength, and degradation rate is a research difficulty in the field of biomedical materials. Summary of the Invention

[0004] In view of this, the present invention aims to provide a poly (L-lactide)-caprolactone composite material, a preparation method and application thereof, and a vascular stent. The composite material provided by the present invention has excellent toughness, strength, and degradation rate.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a poly (L-lactide)-caprolactone composite material, comprising the following raw materials in percentage by mass: 85-99.9% poly (L-lactide)-caprolactone and 0.1-15% metal oxide;

[0007] The metal oxide includes one or more of ferric oxide, magnesium oxide, zinc oxide and titanium dioxide.

[0008] Preferably, the monomers for preparing the poly (L-lactide-caprolactone) include L-lactide and caprolactone; and the molar ratio of L-lactide to caprolactone is 70:30 to 98:2.

[0009] Preferably, the particle size of the metal oxide is 50-200 nm.

[0010] Preferably, the raw materials further include a silane coupling agent, and the mass percentage of the silane coupling agent is less than or equal to 2%.

[0011] Preferably, the silane coupling agent includes γ-aminopropyltriethoxysilane.

[0012] The present invention also provides a method for preparing the poly (L-lactide)-caprolactone composite material described in the above technical solution, comprising the following steps:

[0013] The poly (L-lactide)-caprolactone and the metal oxide are mixed to obtain the poly (L-lactide)-caprolactone composite material.

[0014] Preferably, the mixing method is solution mixing or melt extrusion mixing; the solution mixing includes the following steps:

[0015] dispersing poly (L-lactide-caprolactone) in an organic solvent to obtain a poly (L-lactide-caprolactone) solution;

[0016] dispersing the metal oxide in an organic solvent to obtain a metal oxide dispersion;

[0017] The poly (L-lactide-caprolactone) solution and the metal oxide dispersion are mixed under mechanical stirring and ultrasonic conditions, and then dried, tableted and crushed in sequence to obtain the poly (L-lactide-caprolactone) composite material.

[0018] Preferably, the temperature of the melt extrusion mixing is 180-230°C.

[0019] The present invention also provides the use of the poly (L-lactide-caprolactone) composite material described in the above technical solution or the poly (L-lactide-caprolactone) composite material prepared by the preparation method described in the above technical solution in the preparation of vascular stents.

[0020] The present invention also provides a vascular stent, which is obtained by 3D printing from the poly (L-lactide-caprolactone) composite material described in the above technical solution or the poly (L-lactide-caprolactone) composite material prepared by the preparation method described in the above technical solution.

[0021] The invention provides a poly (L-lactide)-caprolactone composite material.

[0022] The composite material of the present invention is prepared from poly (L-lactide-caprolactone) (PLCL) and a metal oxide. The metal oxide acts as a heterogeneous nucleating agent, increasing the crystallinity of the PLCL from 25% to 35-40%, thereby enhancing the composite's strength. Furthermore, compared to PLLA, the composite material of the present invention exhibits improved toughness and strength. The metal oxide can also increase the degradation rate of the PLCL polymer. Consequently, the composite material of the present invention combines excellent toughness, strength, and degradation rate.

[0023] Furthermore, especially when the metal oxide is ferric oxide, the elongation at break and the tensile strength of the obtained composite material are significantly improved; and the in vitro degradation rate is also significantly improved; at the same time, it has excellent biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1is the maximum elongation and tensile strength graph of the composite wire;

[0025] Figure 2 Radial force data for different printed vascular stents;

[0026] Figure 3 The following are SEM images of stent rods in different printed vascular stents;

[0027] Figure 4 Mapping diagrams of stent rods in different printed vascular stents;

[0028] Figure 5 is the percentage decrease in the weight-average molecular weight of PLCL in printed vascular stents with different mass percentages of ferric oxide;

[0029] Figure 6 The radial force increase data of vascular stents with different mass percentages of ferric oxide before and after heat treatment are shown in FIG.

[0030] Figure 7 The molecular weight change of heat-treated vascular stents with different mass percentages of ferric oxide during degradation at 50°C;

[0031] Figure 8 The molecular weight change of heat-treated vascular stents with different mass percentages of ferric oxide during degradation at 60°C;

[0032] Figure 9 The crystallinity change of heat-treated vascular stents with different mass percentages of ferric oxide at 50°C during degradation;

[0033] Figure 10 The crystallinity change of heat-treated vascular stents with different mass percentages of ferric oxide at 60℃ during degradation process;

[0034] Figure 11 The weight ratio change of pure PLCL stent and stent containing 2% Fe2O3 by mass during degradation on a shaker at 50°C.

[0035] Figure 12 The radial force data of pure PLCL stent and stent containing 2% Fe2O3 by mass were obtained after degradation on a shaker at 50°C for 0, 1, 3, 7, 14, 28, and 42 days.

[0036] Figure 13 The weight average molecular weight ratio of the pure PLCL stent and the stent containing 2% ferric oxide by mass during degradation on a shaker at 50°C;

[0037] Figure 14The crystallinity curves of pure PLCL stent and stent containing 2% Fe2O3 by mass during degradation on a shaker at 50°C.

[0038] Figure 15 Schematic diagram of the structure of a three-dimensional cell culture scaffold;

[0039] Figure 16 This is a CCK-8 image of NIH / 3T3 cells cultured on a three-dimensional cell culture scaffold made of composite materials;

[0040] Figure 17 Live / Dead staining results of NIH / 3T3 cells after culturing on the three-dimensional cell culture scaffold prepared with the composite material for 48 hours;

[0041] Figure 18 The image shows NIH / 3T3 cells stained with rhodamine-labeled phalloidin (red) and DAPI (blue) after being cultured on the three-dimensional cell culture scaffold prepared from the composite material for 48 hours. DETAILED DESCRIPTION

[0042] The present invention provides a poly (L-lactide)-caprolactone composite material, comprising the following raw materials in percentage by weight: 85-99.9% poly (L-lactide)-caprolactone and 0.1-15% metal oxide;

[0043] The metal oxide includes one or more of ferric oxide, magnesium oxide, zinc oxide and titanium dioxide.

[0044] Unless otherwise specified, the raw materials used in the present invention are preferably commercially available products.

[0045] The raw materials used to prepare the poly (L-lactide)-caprolactone composite material provided by the present invention comprise 85% to 99.9% poly (L-lactide)-caprolactone, preferably 85%, 87%, 90%, 92%, 94%, 95%, 97%, 98%, 99%, 99.5%, or 99.9% by mass. In the present invention, the monomers used to prepare the poly (L-lactide)-caprolactone preferably comprise L-lactide and caprolactone; the molar ratio of L-lactide to caprolactone is preferably 70:30 to 98:2, preferably 70:30, 75:25, 80:20, 85:15, 90:10, 95:5, or 98:2. Compared to PLLA, the composite material of the present invention has better toughness and strength.

[0046] The raw materials used to prepare the poly (L-lactide)-caprolactone (PLLC) composite material provided herein include, by mass percentage, 0.1% to 15% metal oxide, preferably 0.1%, 0.5%, 1%, 2%, 5%, 10%, 13%, or 15%. In the present invention, the metal oxide comprises one or more of ferric oxide, magnesium oxide, zinc oxide, and titanium dioxide, preferably one or more of ferric oxide, magnesium oxide, and zinc oxide, and more preferably ferric oxide. In the present invention, the particle size of the metal oxide is preferably 50 to 200 nm, more preferably 100 to 200 nm. In the present invention, the metal oxide acts as a heterogeneous nucleating agent, increasing the crystallinity of PLLC from 25% to 35 to 40%, thereby improving the strength of the composite material. Compared to PLLA, the composite material of the present invention has better toughness and strength. The metal oxide can also increase the degradation rate of the composite material. Therefore, the composite material of the present invention combines excellent toughness, strength, and degradation rate. Furthermore, especially when the metal oxide is ferric oxide, the elongation at break and the tensile strength of the obtained composite material are significantly improved; and the in vitro degradation rate is also significantly improved; at the same time, it has excellent biocompatibility.

[0047] The raw materials used to prepare the poly (L-lactide)-caprolactone composite material provided herein preferably also include a silane coupling agent, preferably γ-aminopropyltriethoxysilane (KH550). The mass percentage of the silane coupling agent is preferably less than or equal to 2%, and more preferably 0.1%, 0.5%, 1%, 1.5%, or 2%. In the present invention, the silane coupling agent modifies the metal oxide, forming a hydrogen bond network with the poly (L-lactide)-caprolactone (PLCL) molecular chains, thereby enhancing the interfacial bonding between the metal oxide and the PLCL matrix.

[0048] In the present invention, the poly (L-lactide)-caprolactone composite material is preferably in the form of particles, filaments, or thin-walled tubes. In the present invention, the diameter of the filaments (the diameter specifically refers to the diameter of the filaments) is preferably 1.75 mm.

[0049] The present invention also provides a method for preparing the poly (L-lactide)-caprolactone composite material described in the above technical solution, comprising the following steps:

[0050] The poly (L-lactide)-caprolactone and the metal oxide are mixed to obtain the poly (L-lactide)-caprolactone composite material.

[0051] In the present invention, the mixing method is preferably solution mixing or melt extrusion mixing.

[0052] In the present invention, the poly (L-lactide)-caprolactone composite material obtained by solution mixing is preferably in the form of particles; and the poly (L-lactide)-caprolactone composite material obtained by melt extrusion mixing is preferably in the form of wire or thin-walled tube.

[0053] In the present invention, the solution mixing preferably comprises the following steps:

[0054] dispersing poly (L-lactide-caprolactone) in an organic solvent to obtain a poly (L-lactide-caprolactone) solution;

[0055] dispersing the metal oxide in an organic solvent to obtain a metal oxide dispersion;

[0056] The poly (L-lactide-caprolactone) solution and the metal oxide dispersion are mixed under mechanical stirring and ultrasonic conditions, and then dried, tableted and crushed in sequence to obtain the poly (L-lactide-caprolactone) composite material.

[0057] In the present invention, the organic solvent preferably includes dichloromethane. The present invention does not impose any specific restrictions on the content of poly-L-lactide-caprolactone in the poly-L-lactide-caprolactone solution, as long as the poly-L-lactide-caprolactone is completely dissolved. The present invention does not impose any specific restrictions on the content of the metal oxide dispersion, as long as the metal oxide is completely dispersed.

[0058] In the present invention, when the preparation raw materials preferably further include a silane coupling agent, the silane coupling agent is preferably dispersed in an organic solvent together with the metal oxide.

[0059] In the present invention, the mechanical stirring speed is preferably 800-1200 rpm, more preferably 800 rpm, 900 rpm, 1000 rpm, 1100 rpm, or 1200 rpm; the ultrasound is preferably provided by an ultrasonic cleaning machine. In the present invention, the mixing time under the conditions of mechanical stirring and ultrasound is preferably not less than 60 minutes, more preferably 60-90 minutes. After mixing under the conditions of mechanical stirring and ultrasound, the resulting system is preferably in a viscous state.

[0060] The present invention does not impose any specific limitation on the drying operation and conditions, as long as the organic solvent can be completely removed.

[0061] In the present invention, the thickness of the tablet obtained by tableting is preferably 1-3 mm, specifically preferably 1 mm, 2 mm or 3 mm; the diameter is preferably 80-100 mm, more preferably 90 mm.

[0062] The present invention does not impose any specific limitation on the crushing method, as long as the particle size of the obtained particles is preferably 1-3 mm.

[0063] In the present invention, when the poly (L-lactide-caprolactone) composite material is preferably in the form of particles, 3D printing is preferably performed to obtain the vascular stent.

[0064] In the present invention, the temperature of the melt extrusion mixing is preferably 180-230°C. In the present invention, the melt extrusion mixing is preferably performed on a twin-screw extruder. In the present invention, the poly-L-lactide-caprolactone composite material obtained by the melt extrusion mixing is preferably in the form of a wire or a thin-walled tube.

[0065] The present invention also provides the use of the poly (L-lactide-caprolactone) composite material described in the above technical solution or the poly (L-lactide-caprolactone) composite material prepared by the preparation method described in the above technical solution in the preparation of vascular stents.

[0066] The present invention also provides a vascular stent, which is obtained by 3D printing from the poly (L-lactide-caprolactone) composite material described in the above technical solution or the poly (L-lactide-caprolactone) composite material prepared by the preparation method described in the above technical solution.

[0067] The present invention does not specifically limit the parameters of the 3D printing, and those skilled in the art may set them according to actual needs.

[0068] After the 3D printing, the present invention preferably further comprises heat treatment, sterilization, crimping and water bath expansion in sequence. In the present invention, the temperature of the water bath expansion is preferably 37°C.

[0069] The poly (L-lactide)-caprolactone composite material, its preparation method and application, and vascular stent provided by the present invention are described in detail below with reference to the examples. However, these examples should not be construed as limiting the scope of protection of the present invention.

[0070] Example 1

[0071] Poly (L-lactide-caprolactone) (the molar percentage of L-lactide and caprolactone is 95:5) is dispersed in dichloromethane to obtain a poly (L-lactide-caprolactone) solution.

[0072] Ferric oxide (particle size of 100 nm) is dispersed in dichloromethane to obtain a ferric oxide dispersion.

[0073] A poly (L-lactide-caprolactone) solution and a ferric oxide dispersion were mixed at different ferric oxide mass percentages of 0%, 0.5%, 1%, 2%, 5% and 10% under mechanical stirring and ultrasonic conditions at 1000 rpm for 60 minutes. The dichloromethane was then removed and the mixture was pressed into tablets with a thickness of 2 mm and a diameter of 90 mm. After crushing, composite particles with a particle size of 1 to 3 mm were obtained.

[0074] The composite particles are 3D printed to obtain printed vascular stents.

[0075] The printed vascular stent is then subjected to heat treatment and sterilization in sequence to obtain a heat-treated vascular stent.

[0076] The heat-treated vascular stent was pressed and expanded in a 37° C. water bath in sequence to obtain an expanded vascular stent.

[0077] Example 2

[0078] Poly (L-lactide-caprolactone) (the molar ratio of L-lactide to caprolactone is 95:5) and the metal oxide ferric oxide (particle size of 100 nm) were melt-extruded using a twin-screw extruder to obtain composite wires with a wire diameter of 1.75 mm. The composite wires were used to study the mechanical properties.

[0079] In the composite material wire, the mass percentage of ferric oxide is 0, 0.5%, 1%, 2%, 5% or 10%.

[0080] Example 3

[0081] The difference from Example 1 is that the metal oxide ferric oxide is replaced by magnesium oxide with a particle size of 100 nm, and the mass percentages of magnesium oxide are 0%, 0.5%, 1%, and 2%, respectively.

[0082] Example 4

[0083] The difference from Example 2 is that the metal oxide ferric oxide is replaced by magnesium oxide with a particle size of 100 nm.

[0084] In the composite material wire, the mass percentage of magnesium oxide is 0%, 0.5%, 1% or 2%.

[0085] Example 5

[0086] The difference from Example 1 is that the metal oxide ferric oxide is replaced by zinc oxide with a particle size of 100 nm, and the mass percentages of zinc oxide are 0%, 0.5%, 1%, and 2%, respectively.

[0087] Example 6

[0088] The difference from Example 2 is that the metal oxide ferric oxide is replaced by zinc oxide with a particle size of 100 nm.

[0089] In the composite material wire, the mass percentage of zinc oxide is 0%, 0.5%, 1% or 2%.

[0090] Example 7

[0091] The difference from Example 1 is that the preparation comprises the following raw materials in a mass ratio: 98% poly (L-lactide-caprolactone) (the molar percentage of L-lactide and caprolactone is 95:5), 1.5% ferric oxide, and 0.5% γ-aminopropyltriethoxysilane.

[0092] Example 8

[0093] The difference from Example 1 is that the preparation raw materials are included in the following mass ratio: 98% poly (L-lactide-caprolactone) (the molar percentage of L-lactide and caprolactone is 95:5), 1% ferric oxide, 0.5% magnesium oxide, and 0.5% zinc oxide.

[0094] 1. Performance Characterization

[0095] Figure 1 The maximum elongation and tensile strength of the composite wire are shown in Figure 1, where a is the maximum elongation comparison between the MgO-added group and PLCL; b is the maximum elongation comparison between the ZnO-added group and PLCL; c is the maximum elongation comparison between the Fe2O3-added group and PLCL, and d is the tensile strength comparison. Taking 0.5% MgO as an example, it represents 0.5% MgO / PLCL. Figure 1 It can be seen that with the increase of the proportion of metal oxides, the tensile strength of MgO / PLCL and ZnO / PLCL wires decreased significantly, and was only about 65% of the tensile strength of PLCL wire; while the tensile strength of Fe2O3 / PLCL wire first increased and then decreased.

[0096] Figure 2 The radial force data of different printed vascular stents, where 0.5% MgO is taken as an example, representing 0.5% MgO / PLCL; Figure 2 It can be seen that the radial force of the Fe2O3 / PLCL printed vascular stent first increased and then decreased, among which there was no significant difference in the radial force of the 1%Fe2O3 / PLCL, 2%Fe2O3 / PLCL groups and the PLCL printed vascular stent.

[0097] Figure 3 The SEM images of stent rods in different printed vascular stents are shown in the upper row. The upper row of images are surface SEM images (100 times), and the lower row of images are cross-sectional SEM images (500 times). Taking 2% MgO as an example, it represents 2% MgO / PLCL. Figure 3 The surface SEM images show that the surface of the vascular stents printed with 2%MgO / PLCL, 2%ZnO / PLCL and 2%Fe2O3 / PLCL is smooth, and there is no obvious metal oxide aggregation on the wire rod; the cross-sectional SEM images show that Fe2O3 is best dispersed in PLCL, followed by ZnO and finally MgO.

[0098] Figure 4The mapping diagram of the stent rods in different printed vascular stents, where 2% MgO is taken as an example, representing 2% MgO / PLCL; Figure 4 It can be seen that MgO in the vascular stent printed with 2%MgO / PLCL showed obvious agglomeration, while Fe2O3 and ZnO in the vascular stent printed with 2%Fe2O3 / PLCL and 2%ZnO / PLCL were more evenly distributed.

[0099] Figure 5 is the percentage decrease in the weight-average molecular weight of PLCL in printed vascular stents with different mass percentages of ferric oxide, where 0.5% Fe2O3 is taken as an example, representing 0.5% Fe2O3 / PLCL; Figure 5 It can be seen that as the proportion of Fe2O3 added increases, the percentage decrease in the weight-average molecular weight of the vascular stent after 3D printing first decreases and then increases.

[0100] 2. In vitro degradation studies

[0101] 1. Study the radial force changes of vascular stents before and after heat treatment. The results are as follows Figure 6 As shown, Figure 6 The following is a graph showing the radial force increase of vascular stents with different mass percentages of ferric oxide before and after heat treatment. Taking 0.5% Fe2O3 as an example, it represents 0.5% Fe2O3 / PLCL. Figure 6 It can be seen that the addition of Fe2O3 promotes the increase in the radial force of the vascular stent after heat treatment, which first increases and then decreases with the increase in the amount of Fe2O3 added.

[0102] 2. Degrading the heat-treated vascular stent on a shaker, specifically: immersing the heat-treated vascular stent in a PBS solution, placing it on a shaker, and degrading it at 50°C or 60°C.

[0103] Figure 7 The molecular weight change of heat-treated vascular stents with different mass percentages of ferric oxide during degradation at 50°C, where 0.5% Fe2O3 is taken as an example, representing 0.5% Fe2O3 / PLCL; Figure 8 The molecular weight change of heat-treated vascular stents with different mass percentages of ferric oxide during degradation at 60°C, where 0.5% Fe2O3 is taken as an example, representing 0.5% Fe2O3 / PLCL; Figure 7 and Figure 8 It can be seen that as the addition ratio of Fe2O3 increases, the degradation rate of the heat-treated vascular stent accelerates.

[0104] Figure 9 The crystallinity change of heat-treated vascular stents with different mass percentages of ferric oxide at 50°C during degradation, where 0.5% Fe2O3 is taken as an example, representing 0.5% Fe2O3 / PLCL; Figure 10 The crystallinity changes of heat-treated vascular stents with different mass percentages of ferric oxide at 60°C during degradation, where 0.5% Fe2O3 is taken as an example, representing 0.5% Fe2O3 / PLCL; Figure 9 and Figure 10 It can be seen that as the degradation time increases, the crystallinity of the heat-treated vascular stent increases.

[0105] 3. Immerse the stent in PBS solution, place it in a shaker, and degrade it at 50°C.

[0106] Figure 11 The weight ratio change of pure PLCL stent and stent containing 2% Fe2O3 by mass during degradation on a shaker at 50°C, where 2% Fe2O3 represents stent containing 2% Fe2O3 by mass. Figure 11 It can be seen from the weight change that the change is obvious in the early stage of accelerated degradation, and tends to be gentle at 14 days and 28 days.

[0107] Figure 12 The radial force data of the pure PLCL stent and the stent containing 2% Fe2O3 by mass were obtained after degradation on a shaker at 50°C for 0, 1, 3, 7, 14, 28, and 42 days. 2% Fe2O3 represents the stent containing 2% Fe2O3 by mass. Figure 12 It can be seen that the radial force of the stent that expands the blood vessel first increases and then decreases with the increase of degradation time.

[0108] Figure 13 is the weight average molecular weight ratio of the pure PLCL stent and the stent containing 2% by mass of ferric oxide during degradation on a shaker at 50°C, wherein 2% Fe2O3 represents the stent containing 2% by mass of ferric oxide; Figure 13 It can be seen that the weight average molecular weight of the stent gradually decreases with the increase of degradation time.

[0109] Figure 14 Figure 2 is the crystallinity curve of pure PLCL stent and stent containing 2% Fe2O3 by mass during degradation on a shaker at 50°C, where 2% Fe2O3 represents stent containing 2% Fe2O3 by mass. Figure 14 It can be seen that the crystallinity of the stent increases with the degradation time.

[0110] 3. Compatibility study

[0111] according to Figure 15Schematic diagram of the structure of processing composite material filaments to prepare three-dimensional cell culture scaffolds for compatibility research of composite materials.

[0112] CCK-8 cell counting kit was used to quantitatively evaluate the proliferation of NIH / 3T3 cells. NIH3T3 cells were plated at 2.5×10 4 cells / mL were uniformly seeded on the surface of PLCL, MgO-PLCL, ZnO-PLCL and Fe2O3-PLCL scaffolds (seeding volume 200 μL / well, corresponding to 5×10 cells / mL) 3 cells / well) and cultured in a 37°C, 5% CO2 incubator for 48 hours. Six replicate wells were set up for each group, and a scaffold without cells was reserved as a blank control. After removing the culture medium, 100 μL of fresh culture medium and 10 μL of CCK-8 reagent were added to each well and incubated in the dark for 1.5 hours. The absorbance (OD) was measured at 450 nm using a microplate reader, and the relative cell proliferation rate was calculated using the following formula: Proliferation rate (%) = [(OD of experimental group - OD of blank) / (OD of control group - OD of blank)] × 100%. Note: The control group refers to the cell samples seeded in the PLCL scaffold culture system and data collected at the same time point.

[0113] Figure 16 This is a CCK-8 chart of NIH / 3T3 cells cultured on a three-dimensional cell culture scaffold prepared from composite materials. 2% MgO is used as an example to represent 2% MgO / PLCL. Figure 16 It can be seen that the three groups of PLCL, 2%MgO / PLCL and 2%Fe2O3 / PLCL three-dimensional cell culture scaffolds all have good biocompatibility, while the biocompatibility of the 2%ZnO / PLCL three-dimensional cell culture scaffold is relatively poor.

[0114] Figure 17 Live / Dead staining results of NIH / 3T3 cells after 48 hours of culture on a three-dimensional cell culture scaffold prepared from composite materials. 2% MgO is used as an example to represent 2% MgO / PLCL. Figure 17As can be seen, after 48 hours of co-culture, NIH / 3T3 cells exhibited robust growth and proliferation on the PLCL, 2% MgO / PLCL, and 2% Fe2O3 / PLCL 3D cell culture scaffolds, with a high number of live cells (green fluorescence) and a low number of dead cells (red fluorescence). In contrast, cell growth on the 2% ZnO / PLCL 3D cell culture scaffold was more challenging, with a higher proportion of dead cells (red fluorescence) observed. These findings indicate that PLCL, 2% MgO / PLCL, and 2% Fe2O3 / PLCL have good biocompatibility and support healthy cell growth and proliferation. However, 2% ZnO / PLCL exhibited poor biocompatibility, with a higher number of dead cells. These results are consistent with those from the CCK-8 assay.

[0115] Figure 18 The following is a picture of NIH / 3T3 cells stained with rhodamine-labeled phalloidin (red) and DAPI (blue) after culturing on a three-dimensional cell culture scaffold prepared from composite materials for 48 hours. 2% MgO is used as an example to represent 2% MgO / PLCL. Figure 18 As can be seen, the cytoskeleton was stained using RBITC, while the nuclei were stained using DAPI. This method enables detailed examination of NIH / 3T3 cell morphology. Qualitative immunofluorescence analysis revealed that cells grown on PLCL and 2% Fe2O3 / PLCL 3D cell culture scaffolds exhibited healthy morphology, with long, slender filopodia and a well-organized pattern of actin stress fibers. In contrast, cells grown on 2% ZnO / PLCL 3D cell culture scaffolds grew poorly, demonstrating that 2% MgO / PLCL and 2% Fe2O3 / PLCL are suitable for cell culture and have good biocompatibility. In contrast, 2% ZnO / PLCL exhibited poor biocompatibility, making it less suitable for cell culture applications.

[0116] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. Use of a poly (L-lactide)-caprolactone composite material in the preparation of a vascular stent, wherein the poly (L-lactide)-caprolactone composite material comprises the following raw materials in the following mass percentages: Poly (L-lactide-caprolactone) 98-99.9% and metal oxide 0.1-2%; The metal oxide is ferric oxide; The monomers for preparing the poly L-lactide-caprolactone include L-lactide and caprolactone; the molar ratio of L-lactide to caprolactone is 70:30 to 98:

2.

2. The use according to claim 1, characterized in that The particle size of the metal oxide is 50-200 nm.

3. The use according to claim 1, characterized in that The preparation raw materials also include a silane coupling agent, and the mass percentage of the silane coupling agent is less than or equal to 2%.

4. The use according to claim 3, characterized in that The silane coupling agent includes γ-aminopropyltriethoxysilane.

5. The use according to claim 1, characterized in that The preparation method of the poly (L-lactide)-caprolactone composite material comprises the following steps: The poly (L-lactide)-caprolactone and the metal oxide are mixed to obtain the poly (L-lactide)-caprolactone composite material.

6. The use according to claim 5, characterized in that The mixing method is solution mixing or melt extrusion mixing; the solution mixing includes the following steps: dispersing poly (L-lactide-caprolactone) in an organic solvent to obtain a poly (L-lactide-caprolactone) solution; dispersing the metal oxide in an organic solvent to obtain a metal oxide dispersion; The poly (L-lactide-caprolactone) solution and the metal oxide dispersion are mixed under mechanical stirring and ultrasonic conditions, and then dried, tableted and crushed in sequence to obtain the poly (L-lactide-caprolactone) composite material.

7. The use according to claim 6, characterized in that The temperature of the melt extrusion mixing is 180-230°C.

8. The use according to claim 1, characterized in that The vascular stent is obtained by 3D printing of the poly (L-lactide)-caprolactone composite material.

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