Near-infrared 3D printing silicone rubber composite material for interbody fusion device and preparation method thereof

Abstract

The invention discloses a near-infrared 3D printing silicone rubber composite material for an interbody fusion device and a preparation method of the near-infrared 3D printing silicone rubber composite material. YbCl3. 6H2O and TmCl3. 6H2O / ErCl3. 6H2O / PrCl3. 6H2O are dissolved in water according to the molar ratio (Tm: Er = 1: (0.2-0.5) or Tm: Er: Pr = 1: (0.2-0.5): (0.1-0.3), and NaYbF4: M / Ag is prepared by reacting with EDTA-2Na, NaF and AgNO3; then carrying out SiO2 coating and CTAB (Cetyltrimethyl Ammonium Bromide) / silane modification to obtain silane modified NaYbF4: M coated SiO2 composite particles; and then mixing with a heat / light curing silicone rubber monomer, an initiator and hydroxyapatite to prepare the near-infrared light-heat synergistic curing silicone rubber ink. The material can realize high-precision 3D printing, has good biocompatibility and mechanical properties, and is suitable for preparation of medical silicone rubber products for interbody fusion cages.

Description

Technical Field

[0001] The present invention relates to the technical field of medical material preparation, and particularly relates to a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion cage and a preparation method thereof. Background Art

[0002] Lumbar interbody fusion is an important technique for treating degenerative disc diseases and degenerative scoliosis. Traditional treatment methods are to manufacture an intervertebral fusion cage outside the human body and then install it at a suitable part of the human body. During the operation, in order to reduce the trauma surface, the implanted intervertebral fusion cage often has poor matching with the actual disc size and shape. Moreover, in order to prevent dislocation or movement, additional rivets are needed for fixation. These not only lead to an extended recovery period, but also the rigid fixation is likely to cause secondary injury and discomfort. To solve the above problems, the field of lumbar interbody fusion has recently proposed applying in-situ 3D printing technology to the treatment of degenerative disc diseases and degenerative scoliosis. Using this method, on the premise of making a smaller wound, it is expected to realize a fusion cage with precisely controllable size and dimensions designed according to individual needs, and its modulus can be regulated, and it has good bone growth characteristics. However, one of the biggest challenges of in-situ 3D printing technology is to develop 3D printing materials with excellent comprehensive properties such as suitable printing performance, mechanical properties, and biological properties. Currently, the 3D printing technologies used for the external 3D printing of intervertebral fusion cages mainly include: fused 3D printing technology, ultraviolet light-induced 3D printing technology, powder sintering 3D printing technology, etc. There is high temperature during the processes of fused 3D printing and powder sintering 3D printing, which is not conducive to the in-situ 3D printing of intervertebral fusion cages in the human body; while the ultraviolet light-induced 3D printing process is relatively mild and has been widely used in the medical field (such as intraoral repair, etc.), but the penetration of ultraviolet light in the material is poor. Especially when encountering inorganic solid powders, due to scattering or reflection, the types of 3D printing materials suitable for ultraviolet light curing are limited. Moreover, the currently used ultraviolet light-cured 3D printing organic materials (acrylate-based) have high biological toxicity and are also difficult to be applied to the in-situ 3D printing of intervertebral fusion cages in the human body. These above problems are also the key reasons why the in-situ 3D printing technology has been difficult to be applied in lumbar interbody fusion.

[0003] In view of the urgent need for treating disc diseases and the above-mentioned 3D printing technology problems, silicone rubber is currently recognized as the safest biomedical-grade polymer material due to its low toxicity, good biocompatibility, and adjustable mechanical properties, and has been widely used in the biomedical field. However, the traditional silicone rubber material has poor photocuring 3D printing performance and low mechanical properties, which greatly limits its application in the biomedical field. The present invention provides a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion cage and a preparation method thereof, and develops a near-infrared-assisted extrusion 3D printing material for in-situ manufacturing of an intervertebral fusion cage. Summary of the Invention

[0004] The object of the present invention is to provide a near-infrared 3D printing silicone rubber composite material for intervertebral fusion cages and its preparation method, and to develop a near-infrared assisted extrusion 3D printing material for in-situ manufacturing of intervertebral fusion cages. The near-infrared 3D printing silicone rubber composite material for intervertebral fusion cages mainly consists of silicone rubber, NaYbF4:M / Ag@SiO2 composite particles and hydroxyapatite. Among them, silicone rubber provides 3D printing performance. In the NaYbF4:M / Ag@SiO2 composite particles, NaYbF4:M provides upconversion performance, converting near-infrared light into ultraviolet light to achieve 3D printing function; nano silver provides antibacterial performance, and at the same time uses the Raman enhancement effect to improve the upconversion performance of NaYbF4:M; SiO2 provides biocompatibility, inorganic / organic composite compatibility and mechanical reinforcement characteristics. Hydroxyapatite provides mechanical reinforcement and bone growth functions.

[0005] The preparation method of the near-infrared 3D printing silicone rubber composite material for intervertebral fusion cages includes the following steps:

[0006] (1) Synthesize and prepare near-infrared upconversion NaYbF4:M / Ag composite particles:

[0007] Dissolve YbCl3·6H2O and rare earth metal hydrated trichloride in ultrapure water, then dropwise add an EDTA-2Na solution and stir for 30-50 minutes. Continuously dropwise add a NaF solution and an AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2-3 h. Subsequently, transfer the mixed solution to a polytetrafluoroethylene liner and place it in an autoclave. After reacting at 185-190 °C for 16-20 h, naturally cool to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:M / Ag composite particles;

[0008] (2) NaYbF4:M / Ag@SiO2 composite and its modification:

[0009] Redisperse the near-infrared upconversion NaYbF4:M / Ag composite particles in a mixed solution to form a stable NaYbF4:M / Ag suspension; then add tetraethoxysilane or tetramethoxysilane to the suspension and continue to react at room temperature for 4-6 h to obtain a NaYbF4:M / Ag@SiO2 core-shell composite particle dispersion; then add 3-aminopropyltriethoxysilane or 3-mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 88-92 °C for 10-12 h to obtain a silane-modified NaYbF4:M@SiO2 composite particle. After centrifugation, redisperse it in an acetone solution to form a uniform dispersion.

[0010] (3) Preparation of the extruded 3D printing material:

[0011] Mix the two silicone rubber monomers, namely the thermally initiated polymerizable silicone rubber monomer and the photoinitiated polymerizable silicone rubber macromonomer, to form a uniform silicone rubber monomer mixture. Add the NaYbF4:M@SiO2 composite particle dispersion into the silicone rubber monomer mixture, mechanically stir and disperse it under the condition of 68-72 °C, and remove acetone at the same time. Then add a photoinitiator, a thermal initiator and hydroxyapatite thereto, and mechanically stir and disperse it evenly under ultrasonic assistance. While mechanically stirring, irradiate with 405 nm ultraviolet light to initiate the further polymerization of the side chains of the photoinitiated polymerizable silicone rubber macromonomer until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared-induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0012] Preferably, in step (1), the molar ratio of YbCl3·6H2O to the rare earth metal hydrated trichloride is 8-9:1-2; the rare earth metal hydrated trichloride is selected from one or more of TmCl3·6H2O, ErCl3·6H2O and PrCl3·6H2O, wherein the molar ratio of TmCl3·6H2O, ErCl3·6H2O, PrCl3·6H2O satisfies:

[0013] Tm:Er = 1:0.2-0.5 or Tm:Er:Pr = 1:0.2-0.5:0.1-0.3.

[0014] Preferably, in step (1), the near-infrared upconversion NaYbF4:M / Ag composite particles can emit ultraviolet-visible blue light of 300-450 nm under the excitation wave of 980 nm-1550 nm.

[0015] Preferably, in step (1), the concentration of the EDTA-2Na solution is 0.05-0.2 mol / L; the concentration of the NaF solution is 1.5 mol / L; the concentration of the AgNO3 solution is 0.1 mol / L.

[0016] Preferably, in step (2), the near-infrared upconversion NaYbF4:M / Ag composite particles are dispersed in a mixed solution, and the mixed solution is a mixed solution of ethanol, water and ammonia solution, wherein ethanol:water:ammonia solution = 20:5:1; the concentration of the stable NaYbF4:M / Ag suspension is 5-10.0 mg / ml.

[0017] Preferably, in step (3), the mass ratio of the thermally initiated polymerizable silicone rubber monomer to the photo-initiated polymerizable silicone rubber macromonomer is 1:1 to 3; the thermal initiator accounts for 2 wt% of the thermally initiated polymerizable silicone rubber monomer; the photoinitiator accounts for 1 to 3 wt% of the photo-initiated polymerizable silicone rubber macromonomer; the concentration of the light conversion particles for initiating the further polymerization of the side chains of the photo-initiated polymerizable silicone rubber macromonomer by irradiating with 405 nm ultraviolet light for 3 min to 10 min while mechanically stirring is 1 to 5 wt%; the mass ratio of the hydroxyapatite to the mixed solution of the two silicone rubber monomers is 10 to 20 wt%.

[0018] Preferably, in step (3), the photo-initiated polymerizable silicone rubber macromonomer is a copolymer of methyl siloxane and dimethyl siloxane with methacryloyloxy groups on the side chains; the particle size of the hydroxyapatite is <150 nm.

[0019] Preferably, in step (3), the photoinitiator is selected from one or more of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), 2-hydroxy-2-methyl-1-phenylpropan-1-one (1173), 1-hydroxycyclohexyl phenyl ketone (184), or benzophenone (BP) + amine co-initiator, wherein the amine co-initiator of the benzophenone (BP) + amine co-initiator is selected from one of N-methyldiethanolamine (MDEA), N,N-dimethyl-p-toluidine (DMT), ethyl 4-dimethylaminobenzoate (EDAB), triethanolamine (TEOA), 2-ethylhexyl 4-dimethylaminobenzoate (EHA).

[0020] Preferably, in step (3), the thermal initiator is selected from one of dicumyl peroxide (DCP), benzoyl peroxide (BPO), and chloroplatinic acid-vinyl siloxane complex.

[0021] This application also claims to protect a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, which is prepared by using the preparation method of the near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device described above.

[0022] Due to the application of the above technical solution, the present invention has the following beneficial effects compared with the prior art:

[0023] 1. The present invention selects in-situ photocuring 3D printing silicone rubber composites. In order to balance mechanical properties, biocompatibility and in-situ 3D printing performance, starting from the design of the printing ink formula, a new type of "3D printing ink" - near-infrared induced in-situ photo-thermal co-curing "silicone rubber ink" is developed, and combined with a new preparation method to improve the photocuring 3D printing performance of silicone rubber, realize high-precision 3D printing of silicone rubber prostheses, and simultaneously optimize multiple properties such as biotoxicity and mechanical properties, solving the problem that it is difficult to balance the mechanical properties, biocompatibility and in-situ 3D printing performance of traditional photocuring 3D silicone rubber, and greatly promoting the technical development and application of medical silicone rubber;

[0024] 2. The present invention uses near-infrared photocuring to achieve in-situ 3D printing of high-precision and large-size silicone rubber structures, overcoming the depth limitation of traditional UV curing printing; through the synergistic effect of photoinitiators and thermal initiators, the curing speed is optimized, avoiding the delamination problem of over-curing on the surface layer and uncured on the bottom layer, and improving the printing success rate and structural stability;

[0025] 3. The present invention is suitable for customized in-situ printing of complex structures such as artificial cartilage, intervertebral fusion cages, and ear-nose prostheses, meeting the specific needs of patients. The printing speed is increased by more than 50% compared with the traditional molding method, the operation is simple, the surgical waiting time is shortened, and the professional requirements for medical staff are relatively low, which is more suitable for popularization and promotion; the energy consumption of near-infrared photocuring is lower than that of traditional thermal curing, meeting the trend of green manufacturing. Specific embodiments

[0026] In order to have a clearer understanding of the technical features, objectives and effects of the present invention, the specific implementation methods are described in detail below.

[0027] The present invention will be further described below in conjunction with embodiments, but the present invention is not limited to the following embodiments. The implementation conditions adopted in the embodiments can be further adjusted according to different requirements of specific use, and the implementation conditions not specified are conventional conditions in the industry. The technical features involved in each implementation manner of the present invention can be combined with each other as long as they do not conflict with each other.

[0028] Example 1

[0029] This example provides a preparation method of a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion cage, including the following steps:

[0030] (1) Synthesize and prepare near-infrared upconversion NaYbF4:Tm 0.17 , Er 0.05 / Ag composite particles:

[0031] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O and ErCl3·6H2O, and the molar ratio of TmCl3·6H2O to ErCl3·6H2O satisfies: Tm:Er = 1:0.3) in ultrapure water, then dropwise add 20 mL of 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continuously dropwise add 20 mL of 1.5 mol / L NaF solution and 20 mL of 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles;

[0032] The near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm under the action of a 980 nm excitation wave;

[0033] (2) NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite and its modification:

[0034] Disperse the near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.17 、Er 0.05 / Ag suspension with a concentration of 8 mg / ml; then add 2 ml of tetraethoxysilane to the suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 core-shell composite particles; then add aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particles. After centrifugation, disperse them in an acetone solution to form a homogeneous dispersion;

[0035] (3) Preparation of the extrusion 3D printing material:

[0036] Mix two silicone rubber monomers, namely, a thermally initiated polymerized silicone rubber monomer and a silicone rubber macromonomer obtained by photoinitiating the polymerization of a copolymer (M-PDMS) of a silicone rubber monomer, a methylsiloxane with a methacryloyloxy group in the side chain, and dimethylsiloxane, to form a uniform silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerized silicone rubber monomer to the photoinitiating polymerized silicone rubber macromonomer is 1:2. Add a light-converting NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particle dispersion into the silicone rubber monomer mixture (accounting for 3 wt% of the mass of M-PDMS), mechanically stir and disperse it at 70 °C, and simultaneously remove acetone. Then add a photoinitiator, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), a thermal initiator, benzoyl peroxide (BPO), and hydroxyapatite. The thermal initiator accounts for 2 wt% of the thermally initiated polymerized silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photoinitiating polymerized silicone rubber macromonomer; the hydroxyapatite accounts for 15 wt% of the mass of the two silicone rubber monomer mixtures. Disperse it evenly by mechanical stirring under ultrasonic assistance, and irradiate it with 405 nm ultraviolet light for 3 min while mechanically stirring to initiate further polymerization of the side chain of M-PDMS until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared-induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0037] Example 2

[0038] This example provides a preparation method for a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, including the following steps:

[0039] (1) Synthesize and prepare near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag composite particles:

[0040] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O, and the molar ratio of TmCl3·6H2O, ErCl3·6H2O, PrCl3·6H2O satisfies: Tm:Er:Pr = 1:0.4:0.3) in ultrapure water, then add dropwise 20 mL of a 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continuously add dropwise 20 mL of a 1.5 mol / L NaF solution and 20 mL of a 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag composite particles;

[0041] The near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm under the action of a 1080 nm excitation wave;

[0042] (2) NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag@SiO2 composite and its modification:

[0043] Disperse the near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag composite particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag suspension, and the concentration of the suspension is 8 mg / ml; then add 2 ml of tetraethoxysilane to the suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.13 、Er 0.05 、Pr 0.04 / Ag / @SiO2 core-shell composite particles; then add aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane thereto; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.13, Er 0.05 , Pr 0.04 The / Ag@SiO2 composite particles are centrifuged and then redispersed in an acetone solution to form a homogeneous dispersion.

[0044] (3) Preparation of the extrusion 3D printing material:

[0045] Two silicone rubber monomers, namely, a thermally initiated polymerization silicone rubber monomer for biological use ZY-2 special silicone rubber and a photo-initiated polymerization silicone rubber macromonomer modified polydimethylsiloxane (M-PDMS), are mixed to form a homogeneous silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerization silicone rubber monomer to the photo-initiated polymerization silicone rubber macromonomer is 1:2. NaYbF4:Tm 0.13 , Er 0.05 , Pr 0.04 / Ag@SiO2 composite particle dispersion (3 wt%) is added to the silicone rubber monomer mixture, mechanically stirred and dispersed at 70 °C, while removing acetone. Then, a photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), a thermal initiator benzoyl peroxide (BPO), and hydroxyapatite are added thereto. The thermal initiator accounts for 2 wt% of the thermally initiated polymerization silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photo-initiated polymerization silicone rubber macromonomer; the mass ratio of the hydroxyapatite to the two silicone rubber monomer mixtures is 15 wt%. It is mechanically stirred and dispersed evenly under ultrasonic assistance, and irradiated with 405 nm ultraviolet light for 3 min while mechanically stirring to initiate further polymerization of the M-PDMS side chain until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared induced light-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0046] Example 3

[0047] This example provides a preparation method of a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, including the following steps:

[0048] (1) Synthesis and preparation of near-infrared upconversion NaYbF4:Tm 0.13 , Er 0.07 , Pr 0.02 / Ag composite particles:

[0049] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O, where the molar ratio of TmCl3·6H2O, ErCl3·6H2O, PrCl3·6H2O satisfies: Tm:Er:Pr = 1:0.5:0.2) in ultrapure water, then dropwise add 20 mL of a 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continuously dropwise add 20 mL of a 1.5 mol / L NaF solution and 20 mL of a 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag composite particles;

[0050] The near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm under the action of a 1100 excitation wave;

[0051] (2)NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag@SiO2 composite and its modification:

[0052] Disperse the near-infrared upconversion NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag composite particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag suspension, and the concentration of the suspension is 8 mg / ml; then add 2 ml of tetraethoxysilane to the suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.13 、Er 0.07 、Pr 0.02 / Ag@SiO2 core-shell composite particles; then add aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.13 、Er0.07 , Pr 0.02 The Pr / Ag@SiO2 composite particles are centrifuged and then redispersed in an acetone solution to form a homogeneous dispersion;

[0053] (3) Preparation of the extrusion 3D printing material:

[0054] Two silicone rubber monomers, namely, a silicone rubber monomer obtained by thermal-initiated polymerization of a special silicone rubber ZY-2 for biological use and a silicone rubber macromonomer obtained by photo-initiated polymerization of modified polydimethylsiloxane (M-PDMS), are mixed to form a homogeneous silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerization silicone rubber monomer to the photo-initiated polymerization silicone rubber macromonomer is 1:2. NaYbF4:Tm 0.13 , Er 0.07 , Pr 0.02 / Ag@SiO2 composite particle dispersion (3.0 wt%) is added to the silicone rubber monomer mixture, and mechanical stirring and dispersion are carried out at 70 °C while removing acetone. Then, a photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), a thermal initiator benzoyl peroxide (BPO), and hydroxyapatite are added thereto. The thermal initiator accounts for 2 wt% of the thermally initiated polymerization silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photo-initiated polymerization silicone rubber macromonomer; the mass ratio of the hydroxyapatite to the two silicone rubber monomer mixtures is 1:15 wt%. After being uniformly dispersed by mechanical stirring under ultrasonic assistance and irradiating with 405 nm ultraviolet light for 3 min while mechanically stirring to initiate further polymerization of the side chain of M-PDMS until a gel state is formed, a 3D printing "silicone rubber ink" for a near-infrared-induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device, is obtained.

[0055] Example 4

[0056] This example provides a preparation method of a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, including the following steps:

[0057] (1) Synthesis and preparation of near-infrared upconversion NaYbF4:Tm 0.17 , Er 0.04 , Pr 0.01 / Ag composite particles:

[0058] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O, and the molar ratio of TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O satisfies: Tm:Er:Pr = 1:0.2:0.1) in ultrapure water, then dropwise add 20 mL of a 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continue to dropwise add 20 mL of a 1.5 mol / L NaF solution and 20 mL of a 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool it to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag composite particles;

[0059] The near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm under the action of a 1300 nm excitation wave;

[0060] (2)NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag@SiO2 composite and its modification:

[0061] Disperse the near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag composite particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag suspension, and the concentration of the suspension is 8 mg / ml; then add 2 ml of tetraethoxysilane to the suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.17 、Er 0.04 、Pr 0.01 / Ag@SiO2 core-shell composite particles; then add aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.17, Er 0.04 , Pr 0.01 The Pr / Ag@SiO2 composite particles are centrifuged and then redispersed in an acetone solution to form a uniformly dispersed liquid;

[0062] (3) Preparation of the extrusion 3D printing material:

[0063] Two silicone rubber monomers, namely, a thermally initiated polymerized silicone rubber monomer for biological use ZY-2 special silicone rubber and a photo-initiated polymerized silicone rubber macromonomer modified polydimethylsiloxane (M-PDMS), are mixed to form a uniform silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerized silicone rubber monomer to the photo-initiated polymerized silicone rubber macromonomer is 1:2. NaYbF4:Tm 0.17 , Er 0.04 , Pr 0.01 / Ag@SiO2 composite particle dispersion is added to the silicone rubber monomer mixture (3.0 wt%), mechanically stirred and dispersed at 70 °C, while removing acetone. Then, a photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), a thermal initiator benzoyl peroxide (BPO), and hydroxyapatite (particle size < 150 nm) are added thereto. The thermal initiator accounts for 2 wt% of the thermally initiated polymerized silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photo-initiated polymerized silicone rubber macromonomer; the mass ratio of the hydroxyapatite to the two silicone rubber monomer mixtures is 15 wt%. It is mechanically stirred and dispersed evenly under ultrasonic assistance, and while mechanically stirring, it is irradiated with 405 nm ultraviolet light for 4 min to initiate the further polymerization of the M-PDMS side chain until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared-induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0064] Example 5

[0065] This example provides a preparation method of a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, including the following steps:

[0066] (1) Synthesis and preparation of near-infrared upconversion NaYbF4:Tm 0.17 , Er 0.05 / Ag composite particles:

[0067] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O and ErCl3·6H2O, and the molar ratio of TmCl3·6H2O to ErCl3·6H2O satisfies: Tm:Er = 1:0.3) in ultrapure water, then add dropwise 20 mL of a 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continuously add dropwise 20 mL of a 1.5 mol / L NaF solution and 20 mL of a 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool it to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles;

[0068] The near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles can emit ultraviolet-visible blue light with a wavelength of 300 - 450 nm under the action of a 1050 nm excitation wave;

[0069] (2) NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite and its modification:

[0070] Disperse the near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.17 、Er 0.05 / Ag suspension, and the concentration of the suspension is 8 mg / ml; then add 2 ml of tetraethoxysilane to the NaYbF4:Tm 0.17 、Er 0.05 / Ag suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 core-shell composite particles; then add aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particles. After centrifugation, disperse them in an acetone solution to form a homogeneous dispersion;

[0071] (3) Preparation of the extrusion 3D printing material:

[0072] Mix two silicone rubber monomers, namely the thermally initiated polymerized silicone rubber monomer for biological use and the photo-initiated polymerized silicone rubber macromonomer of modified polydimethylsiloxane (M-PDMS), to form a uniform silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerized silicone rubber monomer to the photo-initiated polymerized silicone rubber macromonomer is 1:3. Add the dispersion liquid of NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particles (3 wt%) into the silicone rubber monomer mixture, mechanically stir and disperse at 70 °C, and remove acetone at the same time. Then add photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), thermal initiator benzoyl peroxide (BPO), and hydroxyapatite (particle size < 150 nm). The thermal initiator accounts for 2 wt% of the thermally initiated polymerized silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photo-initiated polymerized silicone rubber macromonomer; the mass ratio of the hydroxyapatite to the mixture of the two silicone rubber monomers is 15 wt%. Mechanically stir and disperse evenly under ultrasonic assistance, and irradiate with 405 nm ultraviolet light for 4 min while mechanically stirring to initiate the further polymerization of the side chain of M-PDMS until a gel state is formed, obtaining the 3D printing "silicone rubber ink" for the near-infrared induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0073] Example 6

[0074] This example provides a preparation method of a near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, including the following steps:

[0075] (1) Synthesis and preparation of near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles:

[0076] Dissolve 0.9 mmol of YbCl3·6H2O and 0.2 mmol of rare earth metal hydrated trichloride (the rare earth metal hydrated trichloride is TmCl3·6H2O and ErCl3·6H2O, and the molar ratio of TmCl3·6H2O to ErCl3·6H2O satisfies: Tm:Er = 1:0.3) in ultrapure water, then dropwise add 20 mL of a 0.1 mol / L EDTA-2Na solution and stir for 30 minutes. Continue to dropwise add 20 mL of a 1.5 mol / L NaF solution and 20 mL of a 0.1 mol / L AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 h. Subsequently, transfer the mixed solution to a 100 mL polytetrafluoroethylene liner and place it in an autoclave. After reacting at 190 °C for 16 h, naturally cool to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles;

[0077] The near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm under the action of a 1050 nm excitation wave;

[0078] (2) NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite and its modification:

[0079] Disperse the near-infrared upconversion NaYbF4:Tm 0.17 、Er 0.05 / Ag composite inorganic particles in a mixed solution (ethanol:water:ammonia solution = 20:5:1) to form a stable NaYbF4:Tm 0.17 、Er 0.05 / Ag suspension, and the concentration of the suspension is 8 mg / ml; then add 2 ml of tetraethoxysilane to the suspension and react at room temperature for 4 h to obtain NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 core-shell composite particles; then add 3-aminopropyltriethoxysilane or mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 90 °C for 10 h to obtain silane-modified NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particles. After centrifugation, disperse them in an acetone solution to form a uniformly dispersed solution;

[0080] (3) Preparation of the extrusion 3D printing material:

[0081] Mix two silicone rubber monomers, namely, the ZY-2 special silicone rubber monomer for organisms thermally initiated polymerization of silicone rubber monomer and the modified polydimethylsiloxane (M-PDMS) photo-initiated polymerization of silicone rubber macromonomer, to form a uniform silicone rubber monomer mixture. The mass ratio of the thermally initiated polymerization silicone rubber monomer to the photo-initiated polymerization silicone rubber macromonomer is 1:1. Add the NaYbF4:Tm 0.17 、Er 0.05 / Ag@SiO2 composite particle dispersion (3.0 wt%) to the silicone rubber monomer mixture, mechanically stir and disperse it at 70 °C, and at the same time remove acetone. Then add a photoinitiator phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), a thermal initiator benzoyl peroxide (BPO), and hydroxyapatite (particle size < 150 nm). The thermal initiator accounts for 2 wt% of the thermally initiated polymerization silicone rubber monomer; the photoinitiator accounts for 2 wt% of the photo-initiated polymerization silicone rubber macromonomer; the mass ratio of the hydroxyapatite to the two silicone rubber monomer mixtures is 15 wt%. Under ultrasonic assistance, mechanically stir and disperse evenly, and irradiate with 405 nm ultraviolet light for 5 min while mechanically stirring to initiate further polymerization of the M-PDMS side chain until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared-induced light-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

[0082] Comparative Example 1

[0083] This comparative example is based on Example 1 above, and the same parts as those in the above example will not be repeated.

[0084] In this comparative example, in step (3), ultraviolet-visible light irradiation is used for 3D printing.

[0085] Comparative Example 2

[0086] This comparative example is based on Example 1 above, and the same parts as those in the above example will not be repeated.

[0087] In this comparative example, in step (1), AgNO3 is not added.

[0088] Comparative Example 3

[0089] This comparative example is based on Example 1 above, and the same parts as those in the above example will not be repeated.

[0090] In this comparative example, there is no step (2), that is, SiO2 is not coated and surface modification is not carried out.

[0091] Comparative Example 4

[0092] This comparative example is based on Example 1 above, and the same parts as those in the above example will not be repeated.

[0093] In this comparative example, in step (1), TmCl3·6H2O and ErCl3·6H2O are not added.

[0094] Comparative Example 5

[0095] This comparative example is based on the above-mentioned Example 1, and the same parts as the above-mentioned example will not be described in detail.

[0096] In this comparative example, in step (3), the mass ratio of the thermally initiated polymerized silicone rubber monomer to the photo-initiated polymerized silicone rubber macromonomer is 1:4.

[0097] Comparative Example 6

[0098] This comparative example is based on the above-mentioned Example 1, and the same parts as the above-mentioned example will not be described in detail.

[0099] In this comparative example, in step (1), the molar ratio of YbCl3·6H2O to the rare earth metal hydrated trichloride is 10:1.

[0100] Comparative Example 7

[0101] This comparative example is based on the above-mentioned Example 1, and the same parts as the above-mentioned example will not be described in detail.

[0102] In this comparative example, in step (3), the average size of the hydroxyapatite is 2.5 microns.

[0103] The intervertebral fusion cages prepared in the above-mentioned examples and comparative examples were tested with the near-infrared 3D printing silicone rubber composite material. Using a near-infrared assisted extrusion 3D printing device, test specimens were printed to evaluate their 3D printing performance (the change value of the printed size compared with the CAD drawing), mechanical properties (tensile strength and elongation at break), biotoxicity (evaluated using the cell toxicity level of 0-4), antibacterial performance (the number of bacteria per unit area, cfu / cm 2 ) and bone growth characteristics (testing the content of CaP2O6). The test results of the material properties printed with different formulations are shown in Table 1.

[0104] Table 1

[0105]

[0106] It can be seen from Table 1 that the near-infrared 3D printing silicone rubber composite material for intervertebral fusion cages prepared according to the design formula of the present invention has better performance.

[0107] In summary, the present invention selects in-situ 3D printing of silicone rubber composites. In order to balance mechanical properties, biocompatibility, and in-situ 3D printing performance, starting from the design of the printing ink formulation, a new type of "3D printing ink" - near-infrared-induced in-situ photo-thermal co-curing "silicone rubber ink" is developed, and combined with a new preparation method to improve the photo-curing 3D printing performance of silicone rubber, achieve high-precision 3D printing of silicone rubber prostheses, and simultaneously optimize multiple properties such as biotoxicity and mechanical properties, greatly promoting the technological development and application of medical silicone rubber; the present invention uses near-infrared light curing to achieve in-situ printing of high-precision and large-size silicone rubber structures, overcoming the depth limitation of traditional UV curing printing; through the synergistic effect of photoinitiators and thermal initiators, the curing speed is optimized, avoiding the delamination problem of over-curing on the surface layer and uncured bottom layer, and improving the printing success rate; the present invention is applicable to customized printing of complex structures such as artificial cartilage, intervertebral fusion devices, and otorhinolaryngology prostheses, meeting the specific needs of patients, with the printing speed increased by more than 50% compared to the traditional molding method, shortening the surgical waiting time; the energy consumption of near-infrared light curing is lower than that of traditional thermal curing, conforming to the trend of green manufacturing.

[0108] The above-described embodiments merely represent several implementation manners of the present invention, and their descriptions are relatively specific and detailed, but should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention patent shall be subject to the appended claims.

Claims

1. Preparation method of near-infrared 3D printing silicone rubber composite material for intervertebral fusion device, characterized in that, It includes the following steps: (1) Synthesize and prepare near-infrared upconversion NaYbF4:M / Ag composite particles: Dissolve YbCl3·6H2O and rare-earth metal hydrated trichloride in ultrapure water, then add an EDTA-2Na solution and stir for 30 - 50 minutes. Continuously add an NaF solution and an AgNO3 solution to form a colloidal mixture, and stir the obtained colloidal mixture at room temperature for 2 - 3 h. Subsequently, transfer the mixed solution to a polytetrafluoroethylene inner liner and place it in an autoclave. After reacting at 185 - 190 °C for 16 - 20 h, naturally cool it to room temperature. Wash the obtained precipitate with ethanol and deionized water to obtain near-infrared upconversion NaYbF4:M / Ag composite particles; (2) Preparation of NaYbF4:M / Ag@SiO2 composite and its modification: Redisperse the near-infrared upconversion NaYbF4:M / Ag composite particles in a mixed solution to form a stable NaYbF4:M / Ag suspension; then add tetraethoxysilane or tetramethoxysilane to the suspension and continue to react at room temperature for 4 - 6 h to obtain a NaYbF4:M / Ag@SiO2 core-shell composite particle dispersion; then add 3-aminopropyltriethoxysilane or 3-mercaptopropyltrimethoxysilane to it; carry out a condensation reflux reaction at 88 - 92 °C for 10 - 12 h to obtain silane-modified NaYbF4:M@SiO2 composite particles. After centrifugation, redisperse them in an acetone solution to form a uniform dispersion. (3) Preparation of the 3D printing material for extrusion: Mix two silicone rubber monomers, namely a thermally initiated polymerization silicone rubber monomer and a photoinitiated polymerization silicone rubber macromonomer, to form a uniform silicone rubber monomer mixture. Add the NaYbF4:M@SiO2 composite particle dispersion to the silicone rubber monomer mixture, mechanically stir and disperse it at 68 - 72 °C, and simultaneously remove acetone. Then add a photoinitiator, a thermal initiator, and hydroxyapatite, and mechanically stir and disperse them evenly under ultrasonic assistance. While mechanically stirring, irradiate with 405 nm ultraviolet light to initiate the further polymerization of the side chains of the photoinitiated polymerization silicone rubber macromonomer until a gel state is formed, obtaining a 3D printing "silicone rubber ink" for a near-infrared-induced photo-thermal synergistic curing fusion device, that is, the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device.

2. The preparation method of the near-infrared 3D printing silicone rubber composite material for an intervertebral fusion cage according to claim 1, characterized in that, In step (1), the molar ratio of YbCl3·6H2O to the rare-earth metal hydrated trichloride is 8 - 9:1 - 2; the rare-earth metal hydrated trichloride is selected from one or more of TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O. Among them, the molar ratio of TmCl3·6H2O, ErCl3·6H2O, and PrCl3·6H2O satisfies: Tm:Er = 1:0.2 - 0.5 or Tm:Er:Pr = 1:0.2 - 0.5:0.1 - 0.

3.

3. The preparation method of the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device according to claim 1, characterized in that, In step (1), under the excitation of a 980 nm - 1550 nm excitation wave, the near-infrared upconversion NaYbF4:M / Ag composite particles can emit ultraviolet-visible blue light of 300 - 450 nm.

4. The preparation method of the near-infrared 3D printing silicone rubber composite material for an intervertebral fusion cage according to claim 1, characterized in that In step (1), the concentration of the EDTA-2Na solution is 0.05 - 0.2 mol / L; the concentration of the NaF solution is 1.5 mol / L; the concentration of the AgNO3 solution is 0.1 mol / L.

5. The preparation method of the near-infrared 3D printing silicone rubber composite material for intervertebral fusion cages according to claim 1, characterized in that In step (2), the near-infrared upconversion NaYbF4:M / Ag composite particles are dispersed in a mixed solution, which is a mixed solution of ethanol, water and ammonia solution, where ethanol:water:ammonia solution = 20:5:1; the concentration of the stable NaYbF4:M / Ag suspension is 5 - 10.0 mg / ml.

6. The preparation method of the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device according to claim 1, characterized in that, In step (3), the mass ratio of the thermally initiated polymerizable silicone rubber monomer to the photoinitiated polymerizable silicone rubber macromonomer is 1:1 - 3; the thermal initiator accounts for 2 wt% of the thermally initiated polymerizable silicone rubber monomer; the photoinitiator accounts for 1 - 3 wt% of the photoinitiated polymerizable silicone rubber macromonomer; the concentration of the light conversion particles for initiating the further polymerization of the side chains of the photoinitiated polymerizable silicone rubber macromonomer by irradiating with 405 nm ultraviolet light for 3 min - 10 min while mechanically stirring is 1 - 5 wt%; the mass ratio of the hydroxyapatite to the mixed solution of the two silicone rubber monomers is 10 - 20 wt%.

7. The preparation method of the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device according to claim 1, characterized in that, In step (3), the photoinitiated polymerizable silicone rubber macromonomer is a copolymer of methyl siloxane and dimethyl siloxane with methacryloyloxy groups on the side chains; the particle size of the hydroxyapatite is <150 nm.

8. The preparation method of the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device according to claim 1, characterized in that, In step (3), the photoinitiator is selected from one or more of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 1-hydroxycyclohexyl phenyl ketone or benzophenone + amine co-initiator, wherein the amine co-initiator of the benzophenone + amine co-initiator is selected from one of N-methyldiethanolamine, N,N-dimethyl-p-toluidine, ethyl-4-dimethylaminobenzoate, triethanolamine, 2-ethylhexyl-4-dimethylaminobenzoate.

9. The preparation method of the near-infrared 3D printing silicone rubber composite material for the intervertebral fusion device according to claim 1, characterized in that, In step (3), the thermal initiator is selected from one of dicumyl peroxide, benzoyl peroxide, chloroplatinic acid-vinyl siloxane complex.

10. A near-infrared 3D printing silicone rubber composite material for an intervertebral fusion device, characterized in that, It is prepared by using the preparation method of the near-infrared 3D printing silicone rubber composite material for intervertebral fusion device according to any one of claims 1 - 9.

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