A lubricating hydrogel, a hydrophilic lubricating article and a method of making the same

Abstract

This invention discloses a lubricating hydrogel, a hydrophilic lubricating product, and a method for preparing the same. The lubricating hydrogel comprises oxidized hyaluronic acid, photopolymerized biomaterials, and amino-polyethylene glycol-phosphatidylcholine. Amino-polyethylene glycol-phosphatidylcholine and oxidized hyaluronic acid are crosslinked via amide bonds and Schiff base bonds to form a first polymer network. The photopolymerized biomaterials are crosslinked using a photoinitiator to form a second polymer network. This lubricating hydrogel exhibits good biocompatibility. Furthermore, by anchoring the biomimetic phosphatidylcholine head groups within the first polymer network through chemical bonds, a super-lubricating interface can be constructed on the material surface, significantly reducing the coefficient of friction. The second polymer network imparts the necessary mechanical strength and structural stability to the hydrogel. The combination of these two forms a double-crosslinked network structure, which significantly enhances the mechanical strength and load-bearing capacity of the hydrogel, resulting in a product hydrogel that combines excellent lubricity, mechanical properties, and biocompatibility.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, and in particular to a lubricating hydrogel, a hydrophilic lubricating product, and a method for preparing the same. Background Technology

[0002] End-stage treatment of osteoarthritis relies on total knee arthroplasty, creating a significant clinical need for artificial joints. Currently, artificial joint systems typically consist of titanium or cobalt-chromium alloys with ultra-high molecular weight polyethylene (UHMWPE) liners. However, this system has inherent limitations: the friction pair formed by the metal material and the polyethylene liner lacks the super-lubricating properties of a natural joint. Over long-term use, wear particles generated by friction can induce macrophage-mediated inflammatory responses, leading to periprosthetic osteolysis and aseptic loosening. The lack of super-lubricating properties also contributes to the material's susceptibility to wear, typically limiting its lifespan to only 10 to 15 years, necessitating repair or replacement. This is a major cause of long-term artificial joint failure.

[0003] To address the aforementioned issues, existing technologies have explored various modifications to the surface of artificial joints. For example, plasma spraying is used to prepare hydroxyapatite coatings, aiming to promote bone ingrowth for bio-fixation; physical vapor deposition is employed to prepare ceramic coatings such as titanium nitride, which offer high hardness and aesthetic appeal; and cobalt-like carbon coatings are used, leveraging their extremely high hardness and low coefficient of friction to reduce wear. However, all these methods have limitations. Hydroxyapatite coatings primarily address bone integration rather than lubrication and wear resistance, while hard coatings like titanium nitride and cobalt-like carbon face the risk of brittle spalling and lack bioactivity.

[0004] In recent years, hydrogels, as a type of polymer with a highly hydrophilic three-dimensional network structure, have been widely used in the field of biomedical materials due to their ability to absorb and retain large amounts of water without dissolving, their cartilage-like porous three-dimensional structure, and their excellent biocompatibility. However, existing conventional hydrogels typically lack sufficient mechanical properties; when subjected to external forces exceeding their threshold, the network structure undergoes irreversible damage. Therefore, there is an urgent need to develop a hydrophilic lubrication system that combines superlubricity, good mechanical properties, and bioactivity. Summary of the Invention

[0005] The present invention aims to at least solve one of the technical problems existing in the prior art. Therefore, one objective of the present invention is to provide a lubricating hydrogel.

[0006] A second objective of this invention is to provide a method for preparing a lubricating hydrogel.

[0007] A third objective of this invention is to provide a hydrophilic lubricating product.

[0008] The fourth objective of this invention is to provide a method for preparing a hydrophilic lubricating product.

[0009] In a first aspect, the present invention provides a lubricating hydrogel comprising oxidized hyaluronic acid, photopolymerizable biomaterial, and amino-polyethylene glycol-phosphatidylcholine; wherein the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are crosslinked via amide bonds and Schiff base bonds to form a first polymer network, and the photopolymerizable biomaterial is crosslinked via a photoinitiator to form a second polymer network.

[0010] The technical solution of the lubricating hydrogel according to the embodiments of the present invention has at least the following beneficial effects: This lubricating hydrogel comprises oxidized hyaluronic acid, photopolymerized biomaterials, and amino-polyethylene glycol-phosphatidylcholine. This material system exhibits excellent biocompatibility. Specifically, amino-polyethylene glycol-phosphatidylcholine and oxidized hyaluronic acid are cross-linked via amide and Schiff base bonds to form a first polymer network. This anchors the biomimetic phosphatidylcholine (PC) head groups within the cross-linked network of the coating through chemical bonds. The PC groups effectively bind water molecules to form a hydration layer, thereby creating a super-lubricating interface on the material surface, resulting in excellent lubricity and a significant reduction in the coefficient of friction. Furthermore, the first polymer network, formed via Schiff and amide bonds, provides a dynamic and biocompatible framework. The photopolymerized biomaterials, cross-linked through a photoinitiator, form a second polymer network, endowing the lubricating hydrogel with the necessary mechanical strength and structural stability, enabling it to withstand shear or other stresses during use. The combined effect of these polymer networks forms a robust yet flexible double-cross-linked network structure, significantly enhancing the mechanical strength and load-bearing capacity of the hydrogel material. As shown above, this lubricating hydrogel possesses excellent lubricity, mechanical properties, and biocompatibility.

[0011] According to some embodiments of the present invention, the Schiff base bond between the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid is formed by the reaction of the amino group on the amino-polyethylene glycol-phosphatidylcholine with the aldehyde group on the oxidized hyaluronic acid (through a Schiff base reaction), and the amide bond is formed by the reaction of the amino group on the amino-polyethylene glycol-phosphatidylcholine with the carboxyl group on the oxidized hyaluronic acid (through an amidation reaction).

[0012] The polyethylene glycol (PEG) segment in amino-PEG-phosphatidylcholine is a hydrophilic segment, containing several, dozens, or even hundreds of ethylene glycol units. According to some embodiments of the present invention, the PEG segment in amino-PEG-phosphatidylcholine contains 2 to 10 ethylene glycol units. For example, the number of ethylene glycol units in the PEG segment of amino-PEG-phosphatidylcholine can be any value from 2, 3, 4, 5, 6, 7, 8, 9, or 10, or a range of both. In some embodiments, the PEG segment in amino-PEG-phosphatidylcholine contains 3 ethylene glycol units. The PEG segments in amino-PEG-phosphatidylcholine contain fewer ethylene glycol units, making them easier to synthesize and easier to separate and purify (e.g., by column chromatography).

[0013] According to some embodiments of the present invention, the photopolymer biomaterial includes at least one of photocrosslinkable gelatin derivatives and photocrosslinkable natural polysaccharide derivatives.

[0014] In some embodiments, the photocrosslinkable gelatin derivative is a gelatin derivative having carbon-carbon double bonds.

[0015] In some embodiments, the gelatin derivative having carbon-carbon double bonds is methacrylamide gelatin and its derivatives.

[0016] In some embodiments, the photocrosslinkable natural polysaccharide derivative includes at least one of a photocrosslinkable alginate derivative and a photocrosslinkable chitosan derivative.

[0017] Furthermore, in some embodiments, the photocrosslinkable alginate derivative is an alginate derivative having carbon-carbon double bonds, and the photocrosslinkable chitosan derivative is a chitosan derivative having carbon-carbon double bonds.

[0018] Furthermore, in some embodiments, the alginate derivative having carbon-carbon double bonds is sodium methacrylamide; and the chitosan derivative having carbon-carbon double bonds is methacrylamide chitosan and its derivatives.

[0019] According to some embodiments of the present invention, the photoinitiator is any one of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone (i.e., I2959) and lithium phenyl (2,4,6-trimethylbenzoyl)phosphate (i.e., LAP).

[0020] A second aspect of the present invention provides a method for preparing the aforementioned lubricating hydrogel, comprising the following steps: Prepare or provide the oxidized hyaluronic acid, the photopolymerized biomaterial, and the amino-polyethylene glycol-phosphatidylcholine; First, the oxidized hyaluronic acid is subjected to carboxyl activation treatment, and then mixed with the amino-polyethylene glycol-phosphatidylcholine, so that the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are cross-linked through Schiff base reaction and amidation reaction to form a reaction product containing a first polymer network. The reaction product is mixed with the photopolymer biomaterial and a photoinitiator to prepare a hydrogel precursor solution. The hydrogel precursor solution is then subjected to light irradiation to induce cross-linking of the photopolymer biomaterial to form a second polymer network, thereby obtaining the lubricating hydrogel.

[0021] The technical solution of the present invention regarding the preparation method of lubricating hydrogel has at least the following beneficial effects: The lubricating hydrogel preparation method of this invention can produce the lubricating hydrogel described in the first aspect of this invention. Therefore, this lubricating hydrogel preparation method possesses all the aforementioned beneficial effects of the lubricating hydrogel, which will not be elaborated further. Furthermore, each step of the above preparation process is independently controllable, facilitating process standardization and stable control of product quality, and is beneficial for large-scale production.

[0022] According to some embodiments of the present invention, the preparation of the oxidized hyaluronic acid includes: oxidizing hyaluronic acid to obtain oxidized hyaluronic acid.

[0023] In some embodiments, the oxidation treatment includes: mixing hyaluronic acid with an oxidizing agent. The oxidizing agent is typically sodium periodate. Hyaluronic acid contains hydroxyl groups; by oxidizing it to convert the ortho-hydroxyl group into an aldehyde group, it can be subsequently mixed with amino-polyethylene glycol-phosphatidylcholine. The aldehyde group formed after oxidation can react with the amino group on amino-polyethylene glycol-phosphatidylcholine to form a Schiff base bond via a Schiff base reaction, and the carboxyl group present in hyaluronic acid can react with the amino group on amino-polyethylene glycol-phosphatidylcholine via an amidation reaction to form an amide bond. This process oxidizes the hyaluronic acid and crosslinks with amino-polyethylene glycol-phosphatidylcholine to form a reaction product containing a first polymer network.

[0024] In some embodiments, the temperature of the oxidation process is controlled at 10°C to 40°C; preferably, the temperature of the oxidation process is controlled at 20°C to 30°C; more preferably, the temperature of the oxidation process is 25°C.

[0025] In some embodiments, the oxidation treatment is performed under light-protected conditions.

[0026] In some embodiments, the mixing reaction is carried out in water. That is, hyaluronic acid, an oxidant, and water are mixed to carry out the mixing reaction. The water may be deionized water or ultrapure water.

[0027] In some embodiments, hyaluronic acid and the oxidant can be dissolved together in water for a mixing reaction; in other embodiments, hyaluronic acid can be dissolved in water first, and then the oxidant can be added for a mixing reaction. The mixing reaction process may be aided by stirring.

[0028] In some embodiments, the mixing reaction time is controlled to be 20 h to 30 h.

[0029] In some embodiments, the oxidation treatment further includes the step of terminating the reaction by adding a terminator after the mixing reaction is completed. The terminator is typically ethylene glycol. Additionally, after terminating the reaction by adding the terminator, the resulting reaction solution may be dialyzed and lyophilized.

[0030] According to some embodiments of the present invention, the photopolymerized biomaterial is methacrylamide gelatin, which is prepared by reacting methacrylic anhydride with gelatin, centrifuging, dialysis and freeze-drying.

[0031] In some embodiments, the preparation of the methacrylamide gelatin specifically includes: dissolving gelatin in PBS buffer, adding methacrylic anhydride to react, centrifuging to collect the supernatant after the reaction, and then sequentially dialysis and lyophilizing the supernatant to obtain the methacrylamide gelatin. The dialysis can be performed by placing the supernatant into a dialysis bag with a molecular weight cutoff of 14 kDa.

[0032] According to some embodiments of the present invention, the preparation of the amino-polyethylene glycol-phosphatidylcholine includes: mixing and reacting an amino-polyethylene glycol-alcohol with an amino protecting agent, such that the amino protecting group of the amino protecting agent blocks the amino group in the amino-polyethylene glycol-alcohol, to obtain a first intermediate in which the amino group is blocked by the amino protecting group; then, the first intermediate undergoes an esterification reaction with phosphorus oxychloride to obtain a second intermediate; the second intermediate undergoes an alcoholysis reaction with a choline cation source to generate a third intermediate; then, water is added for hydrolysis to obtain an amino-polyethylene glycol-phosphatidylcholine precursor in which the amino group is blocked by the amino protecting group; finally, under the action of a catalyst, the amino-polyethylene glycol-phosphatidylcholine precursor in which the amino group is blocked by the amino protecting group is removed by a hydrogenolysis reaction to obtain amino-polyethylene glycol-phosphatidylcholine.

[0033] The amino protecting agent contains an amino protecting group, and the first intermediate in which the amino group is protected and blocked by the amino protecting group is an amino-polyethylene glycol-alcohol with the amino group blocked by the amino protecting group. In some embodiments, the amino protecting group contained in the amino protecting agent includes at least one of benzyloxycarbonyl (Cbz) and fluorene methoxycarbonyl (Fmoc). Further, in some embodiments, the amino protecting agent includes benzyloxycarbonyl succinimide (Cbz-Osu) and fluorene methoxycarbonyl chloride (Fmoc). At least one of Cl).

[0034] The first intermediate undergoes an esterification reaction with phosphorus oxychloride, simultaneously removing one molecule of HCl to obtain the second intermediate. Specifically, in the esterification reaction process of the first intermediate with phosphorus oxychloride, the hydroxyl group of the first intermediate attacks the phosphorus atom of phosphorus oxychloride, resulting in esterification, and simultaneously removing one molecule of HCl to obtain the second intermediate. In some embodiments, the esterification reaction is carried out in the presence of an organic base; the organic base can be used to neutralize the generated HCl, driving the reaction forward. The organic base may include at least one of triethylamine and pyridine.

[0035] The second intermediate undergoes an alcoholysis reaction with a choline cation source, converting a P-Cl bond on the second intermediate into a PO bond to obtain the third intermediate. Further, the alcoholysis reaction between the second intermediate and the choline cation source is also a nucleophilic substitution reaction. Specifically, the hydroxyl group of the choline cation source acts as a nucleophile, attacking a chlorine atom on the phosphorus atom in the second intermediate, resulting in a nucleophilic substitution reaction to generate a chlorophosphate intermediate, i.e., the third intermediate. In some embodiments, the choline cation source may be a combination of halogenated choline and p-toluenesulfonic acid, a combination of phosphoric acid and p-toluenesulfonic acid, or an organic sulfonate of choline; wherein the halogenated choline may include at least one of brominated choline and choline chloride; and the organic sulfonate of choline may include choline p-toluenesulfonate. In some embodiments, the alcoholysis reaction is carried out in the presence of an organic base (such as pyridine), wherein the organic base may act as an HCl neutralizing agent. In some embodiments, the alcoholysis reaction includes reacting at 0°C for 1-3 hours, followed by reacting at 18-30°C (e.g., room temperature of about 25°C) for 20-30 hours; wherein, the initial reaction at 0°C releases a certain amount of heat, and the subsequent reaction at room temperature generates chlorophosphate intermediates.

[0036] After the alcoholysis reaction is completed, water is added to the third intermediate to carry out a hydrolysis reaction, causing the remaining P-Cl bonds on the third intermediate to hydrolyze, yielding an amino-polyethylene glycol-phosphatidylcholine precursor with the amino group protected by an amino group. In some embodiments, a purification process is further included after the hydrolysis reaction is completed.

[0037] In some embodiments, the catalyst used in the hydrogenolysis reaction includes palladium on carbon.

[0038] The reaction conditions between the aldehyde group and the amino group on oxidized hyaluronic acid are mild, but the reaction between the carboxyl group and the amino group requires the activation of the carboxyl group first. Therefore, before mixing oxidized hyaluronic acid with amino-polyethylene glycol-phosphatidylcholine, the oxidized hyaluronic acid needs to be carboxyl activated.

[0039] According to some embodiments of the present invention, the activators used in the carboxyl activation treatment include 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS).

[0040] In some embodiments, the carboxyl activation treatment includes: dissolving the oxidized hyaluronic acid in MES buffer, and adding EDC and NHS to activate the carboxyl groups of the oxidized hyaluronic acid; wherein, EDC and NHS can be added separately and sequentially, specifically, EDC can be added first for activation for a certain period of time, followed by NHS for activation for a certain period of time. Further, the pH value of the solution system can be controlled within the range of 5.5 to 6.0 during the carboxyl activation treatment process.

[0041] In some embodiments, oxidized hyaluronic acid and amino-polyethylene glycol-phosphatidylcholine are mixed and reacted, and then dialyzed and lyophilized sequentially to obtain a reaction product containing a first polymer network.

[0042] According to some embodiments of the present invention, the hydrogel precursor solution is prepared by mixing the reaction product with the photopolymerizable biomaterial, the photoinitiator, and a solvent. In some embodiments, water is used as the solvent in the preparation of the hydrogel precursor solution; further, ultrapure water may be used as the solvent.

[0043] In some embodiments, the light treatment is ultraviolet light treatment.

[0044] The above-mentioned lubricating hydrogels can be used to construct hydrophilic lubricating products, such as medical implants, catheters, guidewires, and other medical devices. In some embodiments, the lubricating hydrogel can be constructed on the surface of a substrate to form a hydrophilic lubricating coating. For example, a superlubricating coating can be constructed on the surface of a medical implant substrate to form a hydrophilic lubricating coating. Its superlubricating properties can reduce mechanical wear and adhesion between the implant and surrounding tissues. At the same time, its robust and flexible network structure can ensure the excellent mechanical properties of the superhydrophilic lubricating coating and the implant, enabling it to withstand shear forces during implantation and long-term physiological stress in the body. Its excellent biocompatibility can minimize the risk of immune rejection and toxicity of the implant, and is beneficial to cell adhesion and tissue integration. In some embodiments, the medical implant is a bone implant.

[0045] A third aspect of the present invention provides a hydrophilic lubricating article comprising a substrate and a hydrophilic lubricating coating loaded on the surface of the substrate; wherein the hydrophilic lubricating coating is any of the aforementioned lubricating hydrogels of the present invention or a lubricating hydrogel prepared by any of the aforementioned lubricating hydrogels preparation methods.

[0046] The technical solution of this invention regarding hydrophilic lubricating products has at least the following beneficial effects: The hydrophilic lubricating article of the present invention contains the lubricating hydrogel or the lubricating hydrogel prepared by the aforementioned method of the present invention, thereby having all the beneficial effects of the lubricating hydrogel or the lubricating hydrogel preparation method, which will not be elaborated further.

[0047] According to some embodiments of the present invention, the hydrophilic lubricating article further includes an organic adhesive layer disposed between the substrate and the hydrophilic lubricating coating, and connected to the hydrophilic lubricating coating by covalent bonds.

[0048] According to some embodiments of the present invention, the organic adhesive layer is a dopamine layer; the covalent bonds include Schiff base bonds.

[0049] In some embodiments, the organic adhesive layer is a dopamine layer; the covalent bond is a Schiff base bond.

[0050] According to some embodiments of the present invention, the hydrophilic lubricating article is a medical device. The medical device may include, but is not limited to, at least one of medical implants, catheters, and guidewires; in some embodiments, the medical implant is a bone implant.

[0051] According to some embodiments of the present invention, the substrate is a medical substrate, including a polymer substrate, a ceramic substrate, and a metal substrate. In some embodiments, the metal substrate (or medical metal substrate) includes a titanium substrate.

[0052] For medical implants (such as bone implants), existing methods for constructing super-lubricated interfaces through chemical modification or physical treatment typically suffer from the following drawbacks: chemically grafted layers have weak adhesion to the substrate, are prone to degradation and detachment under body fluid erosion and mechanical loads, and lack sufficient lubrication durability; physical coatings are not firmly bonded to the substrate and are prone to peeling during surgery or within the body; hard coatings face the risk of brittle peeling and lack bioactivity. More importantly, existing coating technologies often only address wear or osseointegration issues individually, failing to achieve integrated functionality on both the load-bearing surface (requiring wear-resistant lubrication) and the fixation surface (requiring osseointegration) of artificial joints. To address this, this invention incorporates an organic binder layer, such as a dopamine layer, within the substrate and the hydrophilic lubricating coating. This organic binder layer is covalently linked to the hydrophilic lubricating coating, facilitating a strong and stable bond between the hydrophilic lubricating coating and the substrate. This simultaneously solves both wear and integration / fixation issues, improves lubrication durability, and enables the hydrophilic lubricated product structure to possess super-lubrication, high interfacial bonding strength, and integrated fixation functions.

[0053] In some embodiments, the hydrophilic lubricating article includes a substrate, a hydrophilic lubricating coating loaded on the surface of the substrate, and an organic adhesive layer disposed between the substrate and the hydrophilic lubricating coating. The substrate is a titanium substrate, the hydrophilic lubricating coating is the aforementioned lubricating hydrogel or a lubricating hydrogel prepared by the aforementioned lubricating hydrogel preparation method, and the organic adhesive layer is a dopamine layer. The dopamine layer is connected to the hydrophilic lubricating coating by covalent bonds including Schiff base bonds. By providing a dopamine layer as a connecting module between the titanium substrate and the hydrophilic lubricating coating, it has a stable interfacial bonding ability with both the titanium substrate and the hydrophilic lubricating coating, achieving a strong and stable bond between the hydrophilic lubricating coating and the titanium substrate.

[0054] A fourth aspect of the present invention provides a method for preparing the aforementioned hydrophilic lubricating article, comprising the following steps: Prepare or provide the oxidized hyaluronic acid, the photopolymerized biomaterial, and the amino-polyethylene glycol-phosphatidylcholine; First, the oxidized hyaluronic acid is subjected to carboxyl activation treatment, and then mixed with the amino-polyethylene glycol-phosphatidylcholine, so that the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are cross-linked through Schiff base reaction and amidation reaction to form a reaction product containing a first polymer network. The reaction product is mixed with the photopolymer biomaterial and photoinitiator to form a hydrogel precursor solution. The hydrogel precursor solution is loaded onto the surface of a substrate to form a wet film layer. The wet film layer is subjected to photo-irradiation to initiate cross-linking of the photopolymer biomaterial to form a second polymer network, thereby forming the superhydrophilic lubricating coating and obtaining the hydrophilic lubricating product.

[0055] The technical solution of the present invention regarding the preparation method of hydrophilic lubricating products has at least the following beneficial effects: The preparation method of the superhydrophilic lubricating product in the embodiments of the present invention can produce the aforementioned hydrophilic lubricating product of the present invention. Therefore, the preparation method of the hydrophilic lubricating product has all the beneficial effects of the aforementioned hydrophilic lubricating product, which will not be repeated here.

[0056] The preparation of oxidized hyaluronic acid, photopolymer materials and amino-polyethylene glycol-phosphatidylcholine, as well as the preparation of reactants containing the first polymer network and the formulation of hydrogel precursor solutions, can refer to the aforementioned preparation method of superhydrophilic lubricating coatings, and will not be repeated here.

[0057] In some embodiments, the hydrogel precursor solution is loaded onto the surface of a substrate to form a wet film layer, specifically by immersing the substrate in the hydrogel precursor solution. Further, the substrate can be immersed in the hydrogel precursor solution for a reaction period controlled between 10 h and 24 h. Of course, in some embodiments, the hydrogel precursor solution can also be loaded onto the surface of the substrate by other methods such as coating.

[0058] In some embodiments, the substrate may be pretreated before the hydrogel precursor solution is loaded onto the surface of the substrate. The pretreatment includes sanding, cleaning, and drying. More specifically, the pretreatment includes sanding, cleaning, and drying sequentially. Sanding may specifically be done with 500-3000 grit sandpaper for 5-20 minutes; cleaning may specifically involve ultrasonic cleaning with acetone, alcohol, and deionized water sequentially; drying may be done by natural air drying. In some embodiments, the pretreatment further includes oxygen plasma treatment; specifically, oxygen plasma treatment may be performed after drying.

[0059] According to some embodiments of the present invention, before loading the hydrogel precursor solution onto the surface of the substrate, a dopamine layer is first loaded onto the surface of the substrate, and then the hydrogel precursor solution is loaded onto the dopamine layer to form a wet film layer.

[0060] In some embodiments, the substrate may be pretreated before the dopamine layer is loaded onto its surface. This pretreatment includes sequential sanding, cleaning, drying, and oxygen plasma treatment. This pretreatment removes organic contaminants and oxides from the substrate surface, making it cleaner and more activated, thus facilitating dopamine adhesion.

[0061] In some embodiments, the light treatment is ultraviolet light treatment. Attached Figure Description

[0062] The present invention will be further described below with reference to the accompanying drawings and embodiments, wherein: Figure 1 The NMR spectrum of amino-polyethylene glycol-phosphatidylcholine (PC-NH2) prepared in Example 1 is shown below. Figure 2 This is a schematic diagram of the structure of the lubricating hydrogel in Example 1; Figure 3 This is a schematic flowchart of the preparation method of the hydrophilic lubricating product in Example 2; Figure 4 This is a schematic diagram of the structure of the hydrophilic lubricating product in Example 2; Figure 5 The results show the friction coefficient test results for the titanium substrate and the lubricating hydrogel of Example 1. Detailed Implementation

[0063] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0064] Example 1 This embodiment proposes a lubricating hydrogel comprising oxidized hyaluronic acid (HA-CHO), photopolymerizable biomaterial, and amino-polyethylene glycol-phosphatidylcholine (PC-NH2). The amino-polyethylene glycol-phosphatidylcholine and oxidized hyaluronic acid are crosslinked via amide and Schiff base bonds to form a first polymer network, while the photopolymerizable biomaterial is crosslinked via a photoinitiator to form a second polymer network. In this embodiment, the polyethylene glycol segment in the amino-polyethylene glycol-phosphatidylcholine contains three ethylene glycol units, specifically amino-PEG3-phosphatidylcholine; the photopolymerizable biomaterial is a photocrosslinkable gelatin derivative with carbon-carbon double bonds, specifically methacrylamide gelatin (GelMA).

[0065] This lubricating hydrogel is prepared by a method including the following steps: The chemical synthesis route for the preparation of S1, methacrylamide gelatin (GelMA), is as follows: .

[0066] Weigh 20 g of gelatin powder and add it to PBS buffer at a ratio of 1 g: 10 mL. Stir at 50 °C until completely dissolved. Add 20 mL of methacrylic anhydride (MA) dropwise using a micropump and stir for 2 h. Add an equal volume of preheated PBS to 50 °C for dilution and centrifuge at 1000 rpm for 10 min. Dialyze the supernatant in a 14 kDa dialysis bag for 7 days and freeze-dry to obtain methacrylamide gelatin (GelMA). Store at 4 °C for later use.

[0067] The chemical synthesis route for the preparation of S2 and oxidized hyaluronic acid (HA-CHO) is as follows: .

[0068] Weigh 1g of hyaluronic acid (HA) and completely dissolve it in 100mL of ultrapure water. Add 1.5g of sodium periodate (NaIO4) and oxidize it by stirring at room temperature in the dark for 24 h. Add 2mL of ethylene glycol and stir for 1 h. Dialyze the reaction solution with 7kDa dialysis for 3 days and freeze dry to obtain oxidized hyaluronic acid (HA-CHO). Store it in a refrigerator at 4℃ for later use.

[0069] The design and preparation of S3, amino-polyethylene glycol-phosphatidylcholine (PC-NH2), and its chemical synthesis route are as follows:

[0070] 1. Synthesis of chemical molecule 1a: Referring to the above chemical synthesis route, amino-PEG3-ol (5g, 1eq) was dissolved in tetrahydrofuran (15ml), and the amino protecting reagent benzooxycarbonyl succinimide (Cbz-Osu, 9.2g, 1.1eq) was added. The mixture was stirred at room temperature for 20 h. The tetrahydrofuran solvent was rotary evaporated at 45℃, and the residue was dissolved in dichloromethane. The residue was dissolved in dichloromethane and washed with water 2-3 times. The organic phase was separated and collected, dried with Na2SO4, and the solvent was evaporated to obtain crude product 1a. The product (i.e., the first intermediate 1a) was purified by HPLC (gel permeation chromatography) to obtain 9.27g of product (i.e., the first intermediate 1a), with a yield of 98%.

[0071] 2. Synthesis of chemical molecule 2a: Referring to the above chemical synthesis route, phosphorus oxychloride (POCl3, 2.82 mL, 1.25 eq) was dissolved in dichloromethane (5 mL) and stirred in an ice bath at 0°C. The first intermediate 1a (7 g, 1 eq) synthesized above was dissolved in dichloromethane (8 mL), and triethylamine (Et3N, 4.57 mL, 1.33 eq) was added dropwise using a constant pressure funnel to the above phosphorus oxychloride solution. Esterification was carried out by stirring at room temperature for 1 h to obtain the second intermediate. Pyridine (15.91 mL, 8 eq) and choline p-toluenesulfonate (12.77 g, 2 eq) were slowly added in an ice bath at 0°C. The mixture was stirred at 0°C for 2 h, and the reaction mixture was stirred at room temperature for 24 h to obtain the third intermediate. Water (1 mL) was then added, and the mixture was stirred at room temperature for 1 h to carry out a hydrolysis reaction. Evaporate the solvent, dissolve the residue in anhydrous methanol, evaporate the solvent to dryness, repeat 2-3 times to obtain crude product 2a, which is purified by HPLC (gel permeation chromatography) to obtain 0.02 g of product (2a), with a yield of 90.4%.

[0072] 3. Synthesis of PC-NH2: Product 2a (10.02 g, 1 eq) was dissolved in anhydrous methanol (40 mL), and palladium / carbon (0.5 g) was added. The mixture was stirred in a hydrogenochemical apparatus for 20 h to carry out hydrogenolysis. The solution was filtered, and the solvent was evaporated to obtain PC-NH2. 9.82 g of product was obtained, with a yield of 98%. Its ¹H NMR spectrum is shown below. Figure 1 As shown.

[0073] S4. Preparation of hydrogel primary polymer network: HA-CHO (50 mg, 1 eq) was dissolved in 10 mL of 0.1 mol / L MES buffer. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 35.9 mg, 1.5 eq) was added to the reaction solution, and the solution was stirred at pH 5.5-6.0 for 1 h. N-hydroxysuccinimide (NHS, 28.77 mg, 2 eq) was added to the reaction solution, and the solution was stirred at pH 5.5-6.0 for 2 h. PC-NH2 (137.515 mg, 3.5 eq) was added to the reaction solution, and the mixture was stirred for 24 h. The reaction solution was dialyzed against 7 kDa for 3 days, lyophilized, and HA-PC was obtained and stored at 4 °C for later use.

[0074] S5. Preparation of the hydrogel secondary network: GelMA and HA-PC were added to ultrapure water in equal amounts and stirred for 24 h. Then, 0.5% (w / w) of I2959 photoinitiator was added, and the mixture was stirred in the dark for 30 min to form a hydrogel precursor solution. This solution was then subjected to UV irradiation for 3 min to crosslink the precursor, forming a GelMA-HA-PC hydrogel, i.e., a lubricating hydrogel. Its structural diagram is shown below. Figure 2 As shown.

[0075] Example 2 This embodiment proposes a hydrophilic lubricating product, which is a medical implant. It includes a substrate and a hydrophilic lubricating coating loaded on the surface of the substrate. The substrate is a titanium substrate, and the hydrophilic lubricating coating serves as a lubrication module. Its material is the lubricating hydrogel of Example 1. In addition, in this embodiment, an organic adhesive layer is provided between the substrate and the hydrophilic lubricating coating as a connecting module. The organic adhesive layer is specifically a dopamine layer.

[0076] like Figure 3 As shown, the preparation method of this hydrophilic lubricating product includes the following steps: Methacrylamide gelatin (GelMA), oxidized hyaluronic acid (HA-CHO), and amino-polyethylene glycol-phosphatidylcholine (PC-NH2) were prepared according to steps S1-S3 of the same preparation method as in Example 1. Then, according to step S4 of Example 1, the hydrogel primary polymer network HA-PC was prepared using oxidized hyaluronic acid (HA-CHO) and amino-polyethylene glycol-phosphatidylcholine (PC-NH2). Finally, the hydrogel precursor solution was prepared according to the same procedure as in step S5 of Example 1. A titanium sheet with a diameter of 20 mm and a thickness of 2 mm was sequentially sanded to 2000 grit, then ultrasonically cleaned with acetone, alcohol, and deionized water for 10 minutes each, and allowed to air dry naturally. The cleaned titanium sheet was then subjected to oxygen plasma treatment. 10 mg of commercially available dopamine was weighed and prepared into a 2 mg / mL dopamine solution in 5 mL of 10 mM Tris-HCl buffer. The titanium sheet, which had been pre-treated with oxygen plasma, was immersed in the dopamine solution and reacted for 12 hours. The titanium sheet was then removed and immediately placed in a mold. An appropriate amount of hydrogel precursor solution was added, and ultraviolet light was used to initiate cross-linking polymerization, yielding a hydrophilic lubricating coating product, i.e., a medical implant with a hydrophilic lubricating coating. Figure 4 As shown.

[0077] The friction coefficient was measured using a friction and wear testing machine at 37°C. A hard steel ball was used as the indenter to contact the lubricating hydrogel sample from Example 1, with pure water as the lubricant. A load of 1 N was applied while the sample was subjected to relative motion to measure the friction coefficient. The titanium substrate used in Example 2 was then used instead of the lubricating hydrogel, and the friction coefficient was measured using the same method for comparison. The results are as follows: Figure 5 As shown. By Figure 5 As can be seen, the lubricating hydrogel of Example 1 has excellent lubricity and a significantly lower coefficient of friction compared to the titanium substrate.

[0078] Therefore, the core materials (such as hyaluronic acid, gelatin, and phosphatidylcholine) used in the above embodiments of the present invention for the lubricating hydrogel and hydrophilic lubricating coating products (i.e. medical implants with hydrophilic lubricating coatings) are all of natural origin or inherent components in the body, and have good biocompatibility. This can minimize the immune rejection reaction and toxicity risk of the implants, and is beneficial to cell adhesion and tissue integration. Based on the concept of biomimetic articular cartilage extracellular matrix, this invention covalently binds the superhydrophilic phosphatidylcholine head to a hydrogel / hydrophilic lubricating coating, forming a surface with superlubricity and biocompatibility. Furthermore, the hydrophilic lubricating coating uses a titanium substrate, and through a biomimetic mussel adhesive protein containing catechol, it utilizes dopamine as a strong binder to chelate and connect with the upper hydrogel hydrophilic lubricating coating to the titanium substrate, thus firmly bonding the hydrogel hydrophilic lubricating coating to the substrate surface. Simultaneously, the lubricating hydrogel / hydrophilic lubricating coating possesses a double-crosslinked hydrogel network structure. This structure significantly enhances the coating's mechanical strength and load-bearing capacity while maintaining good hydrophilicity, achieving excellent mechanical properties. This allows the phosphatidylcholine (PC) hydrophilic head group to stably achieve superlubricity, resulting in a hydrogel hydrophilic lubricating coating product that combines low wear rate, high bonding strength, and bioactivity.

[0079] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A lubricating hydrogel, characterized in that, It includes oxidized hyaluronic acid, photopolymerized biomaterials, and amino-polyethylene glycol-phosphatidylcholine; wherein, the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are crosslinked through amide bonds and Schiff base bonds to form a first polymer network, and the photopolymerized biomaterials are crosslinked through a photoinitiator to form a second polymer network.

2. The lubricating hydrogel according to claim 1, characterized in that, The polyethylene glycol segment in the amino-polyethylene glycol-phosphatidylcholine contains 2 to 10 ethylene glycol units.

3. The lubricating hydrogel according to claim 1 or 2, characterized in that, The photopolymer biomaterial includes at least one of photocrosslinkable gelatin derivatives and photocrosslinkable natural polysaccharide derivatives; preferably, the photocrosslinkable natural polysaccharide derivatives include at least one of photocrosslinkable alginate derivatives and photocrosslinkable chitosan derivatives. Preferably, the photocrosslinkable gelatin derivative is a gelatin derivative having carbon-carbon double bonds; the photocrosslinkable alginate derivative is an alginate derivative having carbon-carbon double bonds; and the photocrosslinkable chitosan derivative is a chitosan derivative having carbon-carbon double bonds. More preferably, the gelatin derivative having carbon-carbon double bonds is methacrylamide gelatin and its derivatives; the alginate derivative having carbon-carbon double bonds is methacrylamide sodium alginate; and the chitosan derivative having carbon-carbon double bonds is methacrylamide chitosan and its derivatives.

4. A method for preparing the lubricating hydrogel according to any one of claims 1 to 3, characterized in that, Includes the following steps: Prepare or provide the oxidized hyaluronic acid, the photopolymerized biomaterial, and the amino-polyethylene glycol-phosphatidylcholine; First, the oxidized hyaluronic acid is subjected to carboxyl activation treatment, and then mixed with the amino-polyethylene glycol-phosphatidylcholine, so that the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are cross-linked through Schiff base reaction and amidation reaction to form a reaction product containing a first polymer network. The reaction product is mixed with the photopolymer biomaterial and a photoinitiator to prepare a hydrogel precursor solution. The hydrogel precursor solution is then subjected to light irradiation to induce cross-linking of the photopolymer biomaterial to form a second polymer network, thereby obtaining the lubricating hydrogel.

5. The method for preparing the lubricating hydrogel according to claim 4, characterized in that, The preparation of the amino-polyethylene glycol-phosphatidylcholine includes: mixing and reacting an amino-polyethylene glycol-alcohol with an amino protecting agent, such that the amino protecting group of the amino protecting agent blocks the amino group in the amino-polyethylene glycol-alcohol, to obtain a first intermediate in which the amino group is blocked by the amino protecting group; then, the first intermediate undergoes an esterification reaction with phosphorus oxychloride to obtain a second intermediate; the second intermediate undergoes an alcoholysis reaction with a choline cation source to generate a third intermediate; then, water is added for hydrolysis to obtain an amino-polyethylene glycol-phosphatidylcholine precursor in which the amino group is blocked by the amino protecting group; finally, under the action of a catalyst, the amino-polyethylene glycol-phosphatidylcholine precursor in which the amino group is blocked by the amino protecting group is removed by a hydrogenolysis reaction to obtain amino-polyethylene glycol-phosphatidylcholine.

6. The method for preparing the lubricating hydrogel according to claim 5, characterized in that, The preparation of the amino-polyethylene glycol-phosphatidylcholine satisfies at least one of the following conditions: Condition 1: The amino protecting group contained in the amino protecting agent includes at least one of benzyloxycarbonyl and fluorenyloxycarbonyl; preferably, the amino protecting agent includes at least one of benzyloxycarbonyl succinimide and fluorenyloxycarbonyl chloride; Condition 2: The esterification reaction is carried out in the presence of an organic base; preferably, the organic base includes at least one of triethylamine and pyridine; Condition 3: The choline cation source is selected from a combination of halogenated choline and p-toluenesulfonic acid, a combination of phosphate choline and p-toluenesulfonic acid, or an organic sulfonate of choline; preferably, the organic sulfonate of choline includes choline p-toluenesulfonate. Condition 4: The catalyst comprises palladium on carbon.

7. A hydrophilic lubricating product, characterized in that, It includes a substrate and a hydrophilic lubricating coating loaded on the surface of the substrate; the hydrophilic lubricating coating is a lubricating hydrogel according to any one of claims 1 to 3 or a lubricating hydrogel prepared by the method of any one of claims 4 to 6.

8. The hydrophilic lubricating article according to claim 7, characterized in that, It also includes an organic adhesive layer, which is disposed between the substrate and the hydrophilic lubricating coating and is covalently connected to the hydrophilic lubricating coating; Preferably, the organic adhesive layer is a dopamine layer, and the covalent bonds include Schiff base bonds.

9. The hydrophilic lubricating article according to claim 7, characterized in that, The hydrophilic lubricating product is a medical device; Preferably, the medical device includes at least one of a medical implant, a catheter, and a guidewire.

10. A method for preparing the hydrophilic lubricating article according to any one of claims 8 to 9, characterized in that, Includes the following steps: Prepare or provide the oxidized hyaluronic acid, the photopolymerized biomaterial, and the amino-polyethylene glycol-phosphatidylcholine; First, the oxidized hyaluronic acid is subjected to carboxyl activation treatment, and then mixed with the amino-polyethylene glycol-phosphatidylcholine, so that the amino-polyethylene glycol-phosphatidylcholine and the oxidized hyaluronic acid are cross-linked through Schiff base reaction and amidation reaction to form a reaction product containing a first polymer network. The reaction product is mixed with the photopolymer biomaterial and photoinitiator to form a hydrogel precursor solution. The hydrogel precursor solution is loaded onto the surface of a substrate to form a wet film layer. The wet film layer is subjected to photo-irradiation to initiate cross-linking of the photopolymer biomaterial to form a second polymer network, thereby forming the hydrophilic lubricating coating and obtaining the hydrophilic lubricating product. Preferably, before loading the hydrogel precursor solution onto the surface of the substrate, a dopamine layer is first loaded onto the surface of the substrate, and then the hydrogel precursor solution is loaded onto the dopamine layer to form a wet film layer.

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