Super-lubricating hydrogel microsphere, preparation method and application in osteoarthritis treatment
The preparation of sodium alginate hydrogel microspheres through electrostatic spraying technology and forming a lubricating coating on their surfaces is solved, which solves the structural damage problem of hydrogel microspheres under long-term friction and achieves effective biolubrication in the treatment of osteoarthritis , improves the stability and biocompatibility of microspheres.
Patent Information
- Application Number
- CN202411197969.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-29
- Publication Date
- 2024-12-24
- Estimated Expiration
- 2044-08-29
AI Technical Summary
Existing hydrogel microspheres are prone to structural damage and shape deformation under long-term friction, which affects their lubricating performance and stability. The conventional preparation methods are cumbersome and there is a risk of unclean washing, which affects in vivo applications.
The sodium alginate hydrogel microspheres were prepared by electrostatic spraying technology, and a poly-(2-methacryloyloxyethylphosphorylcholine) lubricated coating was formed on their surface to form a core-shell structure, reducing friction and improving resistance Wear performance.
Through the synergistic effect of hydration layer and ball bearing lubrication, the frictional mechanical stimulation between joint cartilage is reduced, the biological function of cartilage is maintained, and the stability and biocompatibility of superlubricated hydrogel microspheres are improved. It is suitable for the treatment of osteoarthritis .
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Figure CN119174738A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of super-lubricating hydrogel interfaces, and in particular to super-lubricating hydrogel microspheres, a preparation method and application in the treatment of osteoarthritis. Background Art
[0002] Hydrogel microspheres (HMs) are micrometer-sized spherical hydrogels composed of three-dimensional cross-linked hydrophilic polymers with excellent injectability and biocompatibility. HMs can reduce friction at the sliding interface through a rolling mechanism like a ball bearing, making them an attractive candidate for biolubricants. However, continuous friction can cause wear or rupture of the HM surface, causing structural damage, which in turn affects its lubrication performance and stability. In addition, long-term friction can also cause the internal reticular structure of HMs to dissociate or deform, making the shape of the microspheres irregular, thereby affecting their overall performance. Moreover, conventional microfluidic technology requires repeated washing to remove grease from the surface of the microspheres during the preparation of hydrogel microspheres. The process is cumbersome and there is a potential risk of unclean washing, which is not conducive to in vivo application.
[0003] Effective biological lubrication between articular cartilage is essential for maintaining the biological function of cartilage. When articular cartilage is damaged, its friction performance decreases. Abnormal friction mechanical stimulation activates TGF-β1 in the extracellular matrix of cartilage cells, thereby initiating the fibrosis process of chondrocytes, and ultimately leading to continuous degeneration of articular cartilage. Summary of the invention
[0004] The main purpose of the present invention is to propose a super-lubricating hydrogel microsphere, a preparation method and an application in the treatment of osteoarthritis, aiming to improve the abnormal friction force between cartilages and promote cartilage repair by exerting the synergistic effect of hydration lubrication and ball bearing lubrication.
[0005] To achieve the above-mentioned purpose, the present invention provides super-lubricating hydrogel microspheres, which have a core-shell structure, including a core and an outer shell; the core is a sodium alginate hydrogel microsphere, and the outer shell is a hydration layer.
[0006] In one embodiment, the hydration layer is a poly-(2-methacryloyloxyethyl phosphorylcholine) lubricious coating.
[0007] In one embodiment, the poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating has a thickness of 3-5 μm.
[0008] The present invention also provides a method for preparing the super lubricating hydrogel microspheres, comprising the following steps:
[0009] S10, providing a sodium alginate aqueous solution and a calcium chloride aqueous solution;
[0010] S20, spraying the sodium alginate aqueous solution onto the calcium chloride aqueous solution by electrostatic spraying technology to obtain hydrogel microspheres;
[0011] S30, dissolving the hydrogel microspheres in a photoinitiator solution, shaking, and reacting to obtain an intermediate product;
[0012] S40, dispersing the intermediate product in a 2-methacryloyloxyethyl phosphorylcholine (MPC) solution, shaking and irradiating with ultraviolet light, collecting and washing to obtain the super-lubricating hydrogel microspheres.
[0013] In one embodiment, the mass concentration of sodium alginate in the sodium alginate aqueous solution in step S10 is 1-3 wt %; and / or,
[0014] The mass concentration of calcium chloride in the calcium chloride aqueous solution is 3-6wt%.
[0015] In one embodiment, the parameters of the electrostatic spray technology used in step S20 are as follows: positive high voltage is +0.5 to +5 kV, negative high voltage is -5 to -15 kV, and the stainless steel needle model used is 21-30G.
[0016] In one embodiment, the solute of the photoinitiator solution in step S30 includes one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone (I2959), phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (LAP), acyl phosphate, alkyl aromatic ketone derivatives, thioxanthone derivatives and benzophenone; and / or,
[0017] The mass concentration of the solute is 1-3wt%; and / or,
[0018] The shaking time is 0.5-2h.
[0019] In one embodiment, in step S40:
[0020] The mass concentration of the 2-methacryloyloxyethyl phosphorylcholine solution is 1-3wt%; and / or,
[0021] The shaking time is 0.5-2h.
[0022] In one embodiment, the power of the ultraviolet light irradiation in step S40 is 15-60W; and / or,
[0023] The wavelength of the ultraviolet light irradiation is 365-405nm; and / or,
[0024] The duration of the ultraviolet light irradiation is 0.5-2h.
[0025] The present invention also provides an application of super-lubricating hydrogel microspheres in the treatment of osteoarthritis, including the super-lubricating hydrogel microspheres or the super-lubricating hydrogel microspheres prepared by the preparation method of the super-lubricating hydrogel microspheres.
[0026] The super-lubricating hydrogel microspheres provided by the present invention have a core-shell structure, including a core and an outer shell; the core is a sodium alginate hydrogel microsphere, and the outer shell is a hydration layer. The hydration layer formed by the interaction of water molecules and charged ions or zwitterions can greatly reduce friction. Adding a hydration layer on the surface of HMs can achieve the synergistic effect of hydration lubrication and ball bearing lubrication, expanding the application prospects of HMs in the field of biolubrication. Through injection therapy of super-lubricating hydrogel microspheres, super-lubricating hydrogel microspheres can maintain low friction mechanical stimulation between articular cartilages, physically shield the progression of chondrocyte fibrosis, and thus maintain the cartilage phenotype. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.
[0028] Figure 1 A flow chart of the method for preparing super lubricating hydrogel microspheres provided by the present invention;
[0029] Figure 2 This is a light microscopic image of the superlubricating hydrogel microspheres in Example 1 of the present invention;
[0030] Figure 3 This is a graph showing the variation of the coefficient of friction (COF) of the superlubricating hydrogel microspheres during the friction process in Example 1 of the present invention over time;
[0031] Figure 4 This is a live-dead staining image of cells after the super-lubricating hydrogel microspheres and cells were co-incubated in Example 1 of the present invention;
[0032] Figure 5 This is a visual diagram of the superlubricating hydrogel microspheres in Example 1 of the present invention after degradation in pure water for 14 days;
[0033] Figure 6 This is a light microscopic image of the superlubricating hydrogel microspheres in Example 2 of the present invention;
[0034] Figure 7 This is a fluorescent staining image of the superlubricating hydrogel microspheres in Example 2 of the present invention, wherein: Figure 7 (a) before dyeing, Figure 7 (b) after dyeing;
[0035] Figure 8 Fourier infrared spectra of the super lubricating hydrogel microspheres provided in Example 1 of the present invention and the hydrogel microspheres provided in Comparative Example 1;
[0036] Fig. 9 This is a comparison chart of the coefficient of friction (COF) of the super lubricating hydrogel microspheres provided in Example 1 of the present invention and the hydrogel microspheres provided in Comparative Example 1.
[0037] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION
[0038] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0039] It should be noted that if there are descriptions involving "first", "second", etc. in the embodiments of the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features limited to "first" and "second" may explicitly or implicitly include at least one of the features. In addition, if "and / or" or "and / or" appears in the full text, its meaning includes three parallel schemes. Taking "A and / or B" as an example, it includes scheme A, or scheme B, or a scheme that satisfies both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the ability of ordinary technicians in this field to implement. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.
[0040] Long-term friction can cause the internal network structure of HMs to dissociate or deform, making the shape of the microspheres irregular, thereby affecting their overall performance. The present invention uses electrostatic spraying technology to prepare hydrogel microspheres and perform surface modification on them to enhance their anti-friction performance and potential for application in tissue repair in vivo.
[0041] The present invention provides a super-lubricating hydrogel microsphere, which has a core-shell structure, including a core and an outer shell; the core is a sodium alginate hydrogel microsphere, and the outer shell is a hydration layer. The sodium alginate hydrogel microsphere as the core provides a stable structural basis, while the hydration layer as the outer shell can lock water molecules in the surrounding environment, thereby reducing friction during movement.
[0042] In one embodiment of the present invention, the hydration layer is a poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating. The polymer chain contains a large number of hydrophilic groups, which can be tightly combined with water molecules to form a thin hydration layer. The water molecules in the hydration layer can move relatively freely, so that the hydration layer has a certain fluidity and self-adaptability. This dynamic structure helps to continuously replenish the lubricating layer during the friction process and maintain its lubricating properties.
[0043] In one embodiment of the present invention, the thickness of the poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating is 3-5 μm. The lubricating coating of this thickness can fully exert the hydration lubricating effect of PMPC, and a slight increase in size will not cause changes in the structure and performance of the hydrogel microspheres themselves.
[0044] The present invention also provides a method for preparing the super lubricating hydrogel microspheres. Since the preparation method adopts all the technical solutions of all the above embodiments, it at least has all the beneficial effects brought by the technical solutions of the above embodiments, which will not be described one by one here. Figure 1 As shown, the preparation method comprises the following steps:
[0045] S10, providing a sodium alginate aqueous solution and a calcium chloride aqueous solution;
[0046] S20, spraying the sodium alginate aqueous solution onto the calcium chloride aqueous solution by electrostatic spraying technology to obtain hydrogel microspheres;
[0047] S30, dissolving the hydrogel microspheres in a photoinitiator solution, shaking, and reacting to obtain an intermediate product;
[0048] S40, dispersing the intermediate product in a 2-methacryloyloxyethyl phosphorylcholine solution, shaking and irradiating with ultraviolet light, collecting and washing to obtain the super lubricating hydrogel microspheres.
[0049] The sodium alginate aqueous solution is the hydrogel precursor solution, and the calcium chloride aqueous solution is the crosslinker solution. The calcium ions in the calcium chloride aqueous solution react with the carboxylic acid groups in the sodium alginate to form a gel. The electrostatic spraying technology can efficiently produce uniform hydrogel microspheres. By oscillating the reaction in the photoinitiator solution, specific chemical molecules and functional groups can be introduced to enhance the physical and chemical properties of the hydrogel microspheres.
[0050] The introduction of 2-methacryloyloxyethyl phosphorylcholine can increase the hydrophilicity of the intermediate product surface, allowing the intermediate product to better interact with water molecules during movement. With enhanced hydrophilicity, water molecules can form a hydration layer on the hydrogel surface, which can reduce the direct contact between super-lubricating hydrogel microspheres, thereby reducing the friction coefficient. Ultraviolet light can excite the chemical bonds in the 2-methacryloyloxyethyl phosphorylcholine molecules, making them more active and easy to react with the intermediate product.
[0051] In one embodiment of the present invention, the mass concentration of sodium alginate in the sodium alginate aqueous solution in step S10 is 1-3 wt %. Within this concentration range, sodium alginate can provide a suitable viscosity and stability.
[0052] The mass concentration of calcium chloride in the calcium chloride aqueous solution is 3-6wt%. A higher calcium chloride concentration can accelerate the cross-linking rate, but too high a concentration may lead to excessive cross-linking, affecting the flexibility and mechanical properties of the super-lubricating hydrogel microspheres. Within the range of 3-6wt%, the flexibility and mechanical properties of the super-lubricating hydrogel microspheres can be improved while ensuring the cross-linking rate.
[0053] In one embodiment of the present invention, the parameters of the electrostatic spray technology used in step S20 are as follows: positive high voltage is +0.5 to +5 kV, negative high voltage is -5 to -15 kV, and the stainless steel needle used is 21-30G. The electrostatic spray technology is equivalent to applying an electric charge to sodium alginate. Under the action of the high voltage electric field, the sprayed droplets repel each other, which helps to form smaller microspheres. The applied voltage difference is high, which helps to produce a stable spray effect, and the needle diameter is small, which can produce fine droplets.
[0054] In one embodiment of the present invention, the solute of the photoinitiator solution described in step S30 includes one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, acyl phosphate, alkyl aromatic ketone derivative, thioxanthone derivative and benzophenone. The photoinitiator can generate free radicals under the irradiation of light of a specific wavelength, and these free radicals can trigger the cross-linking reaction of 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer on the surface of the hydrogel microsphere. By controlling the intensity and time of the light irradiation, the degree and speed of cross-linking can be accurately controlled. 2-Hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone has good solubility and high photosensitivity, and can effectively generate free radicals under ultraviolet irradiation, thereby initiating the polymerization of MPC monomers to form PMPC modified on the surface of the hydrogel microspheres. Phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt is suitable for monomer molecules requiring higher cross-linking strength and heat resistance and for polymerization reactions that require use as materials for in vivo applications due to its excellent thermal stability, photosensitivity and low cytotoxicity.
[0055] In one embodiment of the present invention, the mass concentration of the solute in step S30 is 1-3 wt %. Within this concentration range, the photoinitiator can enter the hydrogel microspheres and accumulate on the surface of the microspheres by virtue of the hydrogel microspheres' swelling properties.
[0056] In one embodiment of the present invention, the shaking time in step S30 is 0.5-2 hours. The shaking ensures that the hydrogel microspheres are in uniform contact with the photoinitiator, thereby promoting the chemical reaction and generating the target intermediate product. When the shaking time is within this range, the photoinitiator is evenly mixed in the generated intermediate product.
[0057] In one embodiment of the present invention, the mass concentration of the 2-methacryloyloxyethyl phosphorylcholine solution in step S40 is 1-3wt%. Within this range, the hydrophilicity of the surface of the intermediate product is improved, and the intermediate product can better interact with water molecules during movement, and the water molecules can form a hydration layer on the surface of the hydrogel, which can reduce the direct contact between the superlubricating hydrogel microspheres, thereby reducing the friction coefficient.
[0058] In one embodiment of the present invention, the shaking time in step S40 is 0.5-2 hours. Within this time range, the intermediate product is dispersed evenly in the 2-methacryloyloxyethyl phosphorylcholine solution.
[0059] In one embodiment of the present invention, the power of the ultraviolet light irradiation in step S40 is 15-60 W. Under this power, the hydrogel microspheres can be free from the interference of high temperature and can maintain a good shape.
[0060] In one embodiment of the present invention, the wavelength of the ultraviolet light irradiation in step S40 is 365-405 nm, which belongs to UVA (long-wave ultraviolet light), and can polymerize MPC monomers to form PMPC super-lubricating coatings.
[0061] In one embodiment of the present invention, the duration of ultraviolet irradiation in step S40 is 0.5-2 hours. After 0.5-2 hours of ultraviolet irradiation, MPC will polymerize under the action of the photoinitiator and ultraviolet irradiation and form a PMPC super-lubricating coating on the surface of the hydrogel microspheres.
[0062] The present invention also provides an application of superlubricating hydrogel microspheres in the treatment of osteoarthritis, including the superlubricating hydrogel microspheres or the superlubricating hydrogel microspheres prepared by the preparation method of the superlubricating hydrogel microspheres. Since this application adopts all the technical solutions of all the above embodiments, it has at least all the beneficial effects brought by the technical solutions of the above embodiments, which will not be repeated here one by one.
[0063] The formed PMPC superlubricating coating (i.e., hydration layer) can greatly reduce friction. Therefore, adding a hydration layer to HMs can achieve the synergistic effect of hydration lubrication and ball bearing lubrication, expanding the application of HMs in the treatment of osteoarthritis.
[0064] Example 1
[0065] This embodiment provides a method for preparing super lubricating hydrogel microspheres, comprising the following steps:
[0066] S10, dissolving 200 mg of sodium alginate in 10 mL of deionized water to prepare a 2 wt % sodium alginate aqueous solution, and dissolving 3 g of calcium chloride in 100 mL of deionized water to prepare a 3 wt % calcium chloride aqueous solution;
[0067] S20, draw 10mL of the sodium alginate aqueous solution with a 10mL syringe and place it on the pusher, use a 30G (inner diameter 150μm) stainless steel needle as a nozzle; connect the positive and negative poles of the power supply, and set the voltage to +2kV for positive high voltage and -10kV for negative high voltage; use a stainless steel container as a receiver, and add 100mL of the calcium chloride solution thereto; then use electrostatic spray technology to cross-link the sodium alginate aqueous solution in the calcium chloride solution to prepare hydrogel microspheres, and the distance between the nozzle and the receiver is set to 15cm;
[0068] S30, dissolving 2 g of photoinitiator I2959 in 100 mL of deionized water to prepare a 2 wt % photoinitiator solution, dispersing the hydrogel microspheres into the photoinitiator solution, shaking, and reacting to obtain an intermediate product;
[0069] S40, dissolving 1g of MPC in 100mL of deionized water to prepare a 1% MPC solution, dispersing the intermediate product in the MPC solution, shaking for 2h and irradiating with ultraviolet light, collecting and washing to obtain the super-lubricating hydrogel microspheres. The power of the ultraviolet light is 15W, the wavelength is 365nm, and the irradiation time is 2h. Under the action of photoinitiator I2959 and ultraviolet light irradiation, MPC will polymerize and form a PMPC super-lubricating coating on the surface of the intermediate product. The microspheres are collected and washed with pure water to obtain super-lubricating hydrogel microspheres.
[0070] The super-lubricating hydrogel microspheres obtained in this embodiment are regular spherical in shape and have a diameter of 150-200 μm (e.g. Figure 2 As shown in Figure 3 As shown in the figure, the superlubricating hydrogel microspheres have excellent lubricating properties. The friction coefficient of the superlubricating hydrogel microspheres tested on a friction and wear tester is stable and low during long-term friction. Figure 4As shown in the figure, the superlubricating hydrogel microspheres have excellent biocompatibility and can support cell adhesion and proliferation. At the same time, the superlubricating hydrogel microspheres have suitable degradability and can be completely degraded within 14 days in a pure water environment ( Figure 5 ).
[0071] Example 2
[0072] Compared with Example 1, the difference is that in step S30, 1 g of photoinitiator LAP is dissolved in 100 mL of deionized water to prepare a 1 wt % photoinitiator solution.
[0073] The super-lubricating hydrogel microspheres obtained in this embodiment are regular spherical in shape and have a diameter of 150-200 μm (e.g. Figure 6 shown).
[0074] from Figure 7 (a) and from Figure 7 As can be seen in (b), after the super-lubricating hydrogel microspheres are stained with DiI, they can be efficiently combined with the poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating PMPC to emit red fluorescence. It can be observed that the thickness of the poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating on the surface of the super-lubricating hydrogel microspheres is about 3-5 μm.
[0075] Comparative Example 1
[0076] This comparative example provides a method for preparing hydrogel microspheres, comprising the following steps:
[0077] 200 mg of sodium alginate was dissolved in 10 mL of deionized water to prepare a 2 wt % sodium alginate aqueous solution, and 3 g of calcium chloride was dissolved in 100 mL of deionized water to prepare a 3 wt % calcium chloride aqueous solution. 10 mL of sodium alginate aqueous solution was drawn with a 10 mL syringe and placed on a pusher, and a 30G (150 μm inner diameter) stainless steel needle was used as a nozzle; the positive and negative poles of the power supply were connected, and the voltage was set to +2 kV for positive high voltage and -10 kV for negative high voltage; a stainless steel container was used as a receiver, and 100 mL of calcium chloride solution was added thereto; then, the sodium alginate aqueous solution was cross-linked in the calcium chloride aqueous solution using electrostatic spray technology to prepare hydrogel microspheres, and the distance between the nozzle and the receiver was set to 15 cm.
[0078] pass Figure 8 As shown in the Fourier transform infrared spectrum test results, a specific absorption peak of MPC (1120 cm -1 , 1500cm -1 , 1700cm -1), indicating that MPC polymerized on the surface of the hydrogel microspheres to form a PMPC lubricating coating; while no specific absorption peak of MPC was detected on the surface of the hydrogel microspheres obtained in Comparative Example 1.
[0079] like Fig. 9 As shown, the surface friction coefficient of the superlubricating hydrogel microspheres prepared in Example 1 and the surface friction coefficient of the hydrogel microspheres prepared in Comparative Example 1 were tested by a friction and wear testing machine. It can be seen that the surface friction coefficient of the hydrogel microspheres prepared in Comparative Example 1 is significantly higher than the surface friction coefficient of the superlubricating hydrogel microspheres prepared in Example 1.
[0080] In Example 1 and Example 2, the hydrogel microspheres were further modified by photopolymerization strategy to prepare superlubricating hydrogel microspheres for the treatment of osteoarthritis. Although the hydrogel microspheres in Comparative Example 1 can also be used for the treatment of osteoarthritis, they only have the function of converting sliding friction into rolling friction and lack the superlubricating coating of the hydrogel microspheres themselves. They are easily damaged by friction with cartilage, resulting in the destruction of the microsphere structure and loss of their original function.
[0081] The above description is only an exemplary embodiment of the present invention, and does not limit the patent scope of the present invention. All equivalent structural changes made by using the contents of the present invention specification and drawings under the technical concept of the present invention, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present invention.
Claims
1. A super lubricating hydrogel microsphere, characterized in that: The super lubricating hydrogel microsphere has a core-shell structure, including a core and an outer shell; the core is a sodium alginate hydrogel microsphere, and the outer shell is a hydration layer.
2. The super lubricating hydrogel microspheres according to claim 1, characterized in that: The hydration layer is a poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating.
3. The super lubricating hydrogel microspheres according to claim 2, characterized in that: The thickness of the poly-(2-methacryloyloxyethyl phosphorylcholine) lubricating coating is 3-5 μm.
4. A method for preparing super lubricating hydrogel microspheres according to any one of claims 1 to 3, characterized in that: The following steps are involved: S10, providing a sodium alginate aqueous solution and a calcium chloride aqueous solution; S20, spraying the sodium alginate aqueous solution onto the calcium chloride aqueous solution by electrostatic spraying technology to obtain hydrogel microspheres; S30, dispersing the hydrogel microspheres in a photoinitiator solution, shaking, and reacting to obtain an intermediate product; S40, dispersing the intermediate product in a 2-methacryloyloxyethyl phosphorylcholine solution, shaking and irradiating with ultraviolet light, collecting and washing to obtain the super-lubricating hydrogel microspheres.
5. The method for preparing super lubricating hydrogel microspheres according to claim 4, characterized in that: The mass concentration of sodium alginate in the sodium alginate aqueous solution in step S10 is 1-3wt%; and / or, The mass concentration of calcium chloride in the calcium chloride aqueous solution is 3-6wt%.
6. The method for preparing super lubricating hydrogel microspheres according to claim 4, characterized in that: The parameters of the electrostatic spray technology used in step S20 are as follows: positive high voltage is +0.5 to +5 kV, negative high voltage is -5 to -15 kV, and the stainless steel needle model used is 21-30G.
7. The method for preparing super lubricating hydrogel microspheres according to claim 4, characterized in that: The solute of the photoinitiator solution in step S30 includes one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone, phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt, acyl phosphate, alkyl aromatic ketone derivative and thioxanthone derivative benzophenone; and / or, The mass concentration of the solute is 1-3wt%; and / or, The shaking time is 0.5-2h.
8. The method for preparing super lubricating hydrogel microspheres according to claim 4, characterized in that: In step S40: The mass concentration of the 2-methacryloyloxyethyl phosphorylcholine solution is 1-3wt%; and / or, The shaking time is 0.5-2h.
9. The method for preparing super lubricating hydrogel microspheres according to claim 4, characterized in that: In step S40: The power of the ultraviolet light irradiation is 15-60W; and / or, The wavelength of the ultraviolet light irradiation is 365-405nm; and / or, The duration of the ultraviolet light irradiation is 0.5-2h.
10. Application of super lubricating hydrogel microspheres in the treatment of osteoarthritis, characterized in that: The invention relates to super-lubricating hydrogel microspheres prepared by the super-lubricating hydrogel microspheres as described in any one of claims 1 to 3 or the super-lubricating hydrogel microspheres prepared by the preparation method of super-lubricating hydrogel microspheres as described in any one of claims 4 to 9.
Citation Information
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