A zwitterionic copolymer for regulating cell adhesion, a preparation method and an injectable hydrogel based thereon and applications thereof

Abstract

The application discloses a kind of amphiprotic ion copolymer of controllable cell adhesion, preparation method and injectable hydrogel based on it and its application, using different proportions of polyethylene glycol diacrylate, 2-[2-(acryloyl ethyl) dimethylamino] ethyl phosphate ester monomer, chain transfer agent and initiator under anaerobic condition, polymer is prepared by reversible addition-fragmentation chain transfer polymerization. The preparation method is simple and controllable, and has clear composition and structure, and the cyclization degree and graft density of the polymer can be controlled by changing the ratio of monomer. At the same time, the polymer and mercapto gelatin can be crosslinked to prepare hydrogel by simple click chemistry. The hydrogel has good biocompatibility, and different proportions can be used to realize the regulation of cell adhesion. The polymer and hydrogel can be applied to antibacterial, cell expansion, injectable tissue engineering hydrogel scaffold and other fields.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and relates to a zwitterionic copolymer that can regulate cell adhesion, its preparation method and application. Background Technology

[0002] Cells, proteins, microorganisms, or macrofouling organisms can accumulate and adhere to material surfaces, causing irreversible damage that leads to performance degradation or even destruction. For example, protein adsorption on the surface of biomedical implant materials can cause platelet adhesion, activating coagulation pathways and leading to inflammation or infection. Generally, the common treatment for this is to replace the infected device, a cumbersome procedure that poses a threat to patient safety. Besides biomaterials, ships and industrial devices also face biofouling, resulting in unnecessary waste. Therefore, reducing or avoiding biofouling on material surfaces is crucial.

[0003] To date, the most commonly used biofouling material is polyethylene glycol (PEG). However, this polymer is prone to oxidation, and the oxidation products have some cytotoxicity. Furthermore, while PEG's antifouling mechanism relies on a hydrated layer formed by hydrogen bonds, the forces between these hydrogen bonds are relatively weak, resulting in unstable antifouling performance.

[0004] Currently, zwitterionic polymers are also excellent antifouling materials. The hydration layer formed by electrostatic interactions gives them antifouling properties, and these properties are relatively stable. In addition, due to their antifouling properties, zwitterionic polymers can provide a good, "clean" environment for cell growth, thus benefiting cell proliferation. Furthermore, traditional cell culture uses the 2D surface of polystyrene bottles, an environment drastically different from the in vivo environment, which can lead to abnormal cell behaviors such as flattening, abnormal polarization, altered responses to drugs and reagents, and loss of differentiation phenotype.

[0005] However, due to the charged groups on the zwitterionic monomers, the grafting density of zwitterionic polymers is generally relatively low. Besides grafting density, the polymer structure also affects the properties of zwitterionic polymers. Different polymer polymerization ratios influence the polymer structure and thus its antifouling effect; cyclic polymers generally exhibit better antifouling performance than linear, brush-like, and hyperbranched polymers. Summary of the Invention

[0006] In order to overcome the shortcomings of the prior art, the present invention aims to provide a zwitterionic copolymer with tunable cell adhesion, a preparation method thereof, and an injectable hydrogel based thereon, as well as its applications, to establish a platform with stable antifouling ability and good biocompatibility that can be used in cell culture, antibacterial materials, or injectable tissue engineering hydrogel scaffolds.

[0007] To achieve the above objectives, the present invention employs the following technical solution:

[0008] This invention discloses a zwitterionic copolymer capable of regulating cell adhesion, the structural formula of which is shown below:

[0009]

[0010] In the formula, a = b = 3 to 30, m = 5 to 50, and n = 5 to 50.

[0011] “r” indicates that the polymer is a random copolymer.

[0012] This invention also discloses a method for preparing the above-mentioned zwitterionic copolymer with adjustable cell adhesion, comprising the following steps:

[0013] 1) Dissolve polyethylene glycol diacrylate, 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, initiator and chain transfer agent in solvent to obtain a mixed solution;

[0014] 2) The mixed solution was subjected to a reversible addition-fragmentation chain transfer radical polymerization reaction under anaerobic conditions, and the reaction process was monitored in real time. When the molecular weight of the reaction reached 1000-100000 Da, the reaction was stopped, and the reaction solution was purified to obtain a zwitterionic copolymer that can regulate cell adhesion.

[0015] Preferably, the reaction molar ratio of polyethylene glycol diacrylate, 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, chain transfer agent and initiator is 1:(0.01-1000):(0.0001-0.01):(0.00005-0.005).

[0016] Preferably, the initiator is 4,4'-azobis(4-cyanopentanoic acid) or 2,2′-azo(2-methylpropionitrile); the chain transfer agent is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, 4-cyano-4-(phenylcarbonylthio)pentanoic acid, 4-cyano-4-[(dodecylthioalkylthiocarbonyl)thioalkyl]pentanoic acid, bis(dodecylthioalkylthiocarbonyl)disulfide, 2-phenyl-2-propylbenzodisulfide or 2-cyano-2-propylbenzodisulfide; and the solvent is acetonitrile or dimethyl sulfoxide.

[0017] Preferably, in step 2), the temperature of the reversible addition-fragmentation chain transfer radical polymerization reaction is 50–100°C.

[0018] Preferably, in step 2), the anaerobic conditions are carried out under an argon atmosphere; real-time monitoring is performed by gel permeation chromatography; and the reaction solution is purified by precipitating the reaction solution three times with diethyl ether or a mixture of diethyl ether and n-hexane to obtain the reaction product, a zwitterionic copolymer that can regulate cell adhesion.

[0019] Preferably, the 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate used is prepared by the following method:

[0020] First, triethylamine, ethanol, and anhydrous tetrahydrofuran were thoroughly stirred until homogeneous. 2-chloro-2-oxo-1,3,2-dioxophosphazenecycloalkane was added dropwise to the mixture at 0°C. The reaction mixture was then stirred at room temperature for 10 hours. After filtration, the reaction mixture was washed with 1:1 diethyl ether and n-hexane, and the mixture was rotary evaporated to obtain the reaction product. 2-(dimethylamino)acrylate and 4-methoxyphenol were added to the reaction product, and the mixture was reacted for 6 days under heating and stirring conditions. The reaction mixture was precipitated three times with tetrahydrofuran to remove impurities. The resulting pale yellow solution was concentrated in a vacuum furnace to obtain 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate.

[0021] This invention also discloses a zwitterionic cyclized polymer hydrogel capable of regulating cell adhesion, which is prepared by mixing the above-mentioned zwitterionic copolymer capable of regulating cell adhesion with a thiolized crosslinking agent; wherein:

[0022] The thiol crosslinking agent is thiolized gelatin, thiolized hyaluronic acid, or thiolized collagen;

[0023] The mass ratio of the zwitterionic copolymer and the crosslinking agent that can regulate cell adhesion is (0.1-1):(0.01-10).

[0024] The present invention also discloses the application of the above-mentioned zwitterionic copolymer with adjustable cell adhesion or the above-mentioned zwitterionic cyclized polymer hydrogel with adjustable cell adhesion in the preparation of biomedical materials.

[0025] Preferably, the biomedical material includes cell culture material, antibacterial material, or injectable tissue-engineered hydrogel scaffold.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] This invention discloses a zwitterionic copolymer capable of regulating cell adhesion. The zwitterionic monomer 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, carrying a charged group, is copolymerized with polyethylene glycol diacrylate to form a polymer with good and stable antifouling properties. As an implant material, it can also reduce immune rejection. Furthermore, the hydrogel formed by the synthesis of the zwitterionic copolymer and thiolized gelatin has an environment similar to the natural extracellular matrix, allowing for precise control of cell culture and proliferation. The degree of polymer cyclization and grafting density can be controlled by changing the monomer ratio. Furthermore, by altering the ratio of different polymers to gelatin, cell adhesion can be regulated, and specific anti-protein adhesion can be achieved.

[0028] The method for preparing the above-mentioned zwitterionic copolymer with controllable cell adhesion disclosed in this invention involves reacting a commercially available polyvinyl glycol monomer with a 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate monomer under anaerobic conditions. Using an initiator and a chain transfer agent, a one-pot reversible addition-fragmentation chain transfer radical polymerization mechanism is employed to prepare the zwitterionic cyclic copolymer. Since the molecular weight of the polymer is easily controlled, the molecular weight of the zwitterionic cyclic copolymer obtained in this invention is controlled within the range of (1000-100000) Da by monitoring the polymer molecular weight. The preparation method disclosed in this invention is simple and the reaction is controllable.

[0029] Furthermore, commonly used 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, 4-cyano-4-(phenylcarbonylthio)valeric acid, 4-cyano-4-[(dodecylthioalkylthiocarbonyl)thioalkyl]valeric acid, bis(dodecylthioalkylthiocarbonyl)disulfide, 2-phenyl-2-propylbenzodisulfide, or 2-cyano-2-propylbenzodisulfide are selected as chain transfer agents, with 4,4'-azobis(4-cyanovaleric acid) or 2,2′-azo(2-methylpropionitrile) as the initiator, resulting in better biocompatibility of the zwitterionic copolymer.

[0030] This invention also discloses a method for synthesizing injectable hydrogels from the above-mentioned zwitterionic cyclized copolymer. The above-mentioned zwitterionic copolymer with adjustable cell adhesion and thiolized gelatin can be used to prepare hydrogels through a simple click chemical crosslinking reaction. The crosslinking reaction temperature is close to the human body temperature and the crosslinking is rapid. Therefore, it is a simple and convenient synthesis method.

[0031] This invention also discloses the application of zwitterionic cyclized copolymers as injectable hydrogels. Because these polymers possess good biocompatibility and cell adhesion can be regulated by using different proportions, they can be applied in fields such as antibacterial applications, cell expansion, and injectable tissue engineering hydrogel scaffolds. Attached Figure Description

[0032] Figure 1 A schematic diagram illustrating the synthesis of 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate monomer;

[0033] Figure 2 The NMR spectrum of the synthesized 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate monomer;

[0034] Figure 3 This is a schematic diagram illustrating the synthesis of zwitterionic cyclized copolymers.

[0035] Figure 4a Gel permeation chromatograms of zwitterionic cyclized copolymers with a molecular weight of 20000 Da, synthesized when the ratio of polyethylene glycol diacrylate to 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate is 0.1:1;

[0036] Figure 4b Gel permeation chromatogram of a zwitterionic cyclized copolymer with a molecular weight of 30,000 Da and a polyethylene glycol diacrylate to 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate ratio of 10:1.

[0037] Figure 5a The NMR spectrum of the copolymer obtained when the ratio of polyethylene glycol diacrylate to 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate is 0.1:1;

[0038] Figure 5b The NMR spectrum of the copolymer obtained when the ratio of polyethylene glycol diacrylate to 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate is 10:1;

[0039] Figure 6a This is a schematic diagram of the physical phase state of the polymer and thiolized gelatin before gelation at 37℃.

[0040] Figure 6b This is a schematic diagram of the physical phase state of the polymer and thiolized gelatin after gelation at 37℃.

[0041] Figure 7a Optical microscope image of human adipose-derived stem cells after forming a hydrogel with a polymer synthesized from polyethylene glycol diacrylate in a ratio of 0.1:1 to 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate and thiolated gelatin;

[0042] Figure 7b Optical micrograph of human adipose-derived stem cells after forming a hydrogel with thiolated gelatin using a polymer synthesized from polyethylene glycol diacrylate in a 10:1 ratio of 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate.

[0043] Figure 8 This is a graph showing the gelation time of hydrogels under different conditions. Detailed Implementation

[0044] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0045] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of the invention described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover a non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0046] The present invention will now be described in further detail with reference to the accompanying drawings:

[0047] This invention discloses a method for preparing zwitterionic cyclized copolymers, comprising the following steps:

[0048] 1) A certain amount of polyethylene glycol diacrylate (PEGDA, molecular weight 200-2000 Da), 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate (MCP-Et), initiator 4,4'-azobis(4-cyanopentanoic acid) (ACVA) or 2,2′-azo(2-methylpropionitrile) (AIBN), and chain transfer agents 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, 4-cyano-4-(phenylcarbonylthio)pentanoic acid, 4-cyano-4- [(dodecylthioalkylthiocarbonyl)thioalkyl]valeric acid, bis(dodecylthioalkylthiocarbonyl)disulfide, 2-phenyl-2-propylbenzodisulfide or 2-cyano-2-propylbenzodisulfide were added to a three-necked flask containing acetonitrile as the reaction solvent and the monomers were fully dissolved by magnetic stirring. The reaction feed molar ratio of PEGDA, MCP-Et and CPADB, ACVA was 1:(0.01-1000):(0.0001-0.01):(0.00005-0.005).

[0049] 2) Remove oxygen using argon gas bubbling for 30 minutes;

[0050] 3) Immerse the three-necked flask in an oil bath preheated to (50-100)℃ to begin the reaction;

[0051] 4) Use gel permeation chromatography to monitor polymer molecular weight;

[0052] 5) When the molecular weight of the reaction approaches the set value of 1000-100000 Da, stop the reaction to quench free radicals;

[0053] 6) The reaction solution was purified by precipitating it three times with diethyl ether.

[0054] See Figure 3 This is a schematic diagram illustrating the synthesis of the aforementioned zwitterionic cyclized copolymer.

[0055] The chemical structural formula of the zwitterionic cyclized copolymer prepared by the above method is as follows:

[0056]

[0057] In the formula: m = 25; n = 10; a = b = 10.

[0058] Example of preparing zwitterionic copolymers that can regulate cell adhesion

[0059] Example 1

[0060] 1) A certain amount of polyethylene glycol diacrylate (PEGDA, molecular weight 575 Da), ethyl 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate (MCP-Et), initiator 4,4'-azobis(4-cyanopentanoic acid) (ACVA), and chain transfer agent 4-cyano-4-(thiobenzoyl)valerate (CPADB) were added to a three-necked flask containing acetonitrile as the reaction solvent. The monomers were fully dissolved by magnetic stirring. The reaction molar ratio of PEGDA575, MCP-Et, CPADB, and ACVA was 1:10:1:0.5.

[0061] 2) Remove oxygen using argon gas bubbling for 30 minutes;

[0062] 3) Immerse the three-necked flask in an oil bath preheated to 60°C to begin the reaction;

[0063] 4) Use gel permeation chromatography to monitor polymer molecular weight;

[0064] 5) After 22 hours of reaction, stop the reaction to quench free radicals;

[0065] 6) The reaction solution was purified by precipitating it three times with diethyl ether.

[0066] 7) The molecular weight of the obtained product is 20000 Da, see [link / reference]. Figure 4a .

[0067] Example 2

[0068] 1) A certain amount of polyethylene glycol diacrylate (PEGDA, molecular weight 575 Da), ethyl 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate (MCP-Et), initiator 4,4'-azobis(4-cyanopentanoic acid) (ACVA), and chain transfer agent 4-cyano-4-(thiobenzoyl)valerate (CPADB) were added to a three-necked flask containing acetonitrile as the reaction solvent. The monomers were fully dissolved by magnetic stirring. The reaction molar ratio of PEGDA575, MCP-Et, CPADB, and ACVA was 100:10:1:0.5.

[0069] 2) Remove oxygen using argon gas bubbling for 30 minutes;

[0070] 3) Immerse the three-necked flask in an oil bath preheated to 60°C to begin the reaction;

[0071] 4) Use gel permeation chromatography to monitor polymer molecular weight;

[0072] 5) After 24 hours of reaction, stop the reaction to quench free radicals;

[0073] 6) The reaction solution was purified by precipitating it three times with diethyl ether.

[0074] 7) The molecular weight of the obtained product is 30,000 Da. See [link to product details]. Figure 4b .

[0075] The synthesis steps of 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate used in this process are as follows:

[0076] First, anhydrous triethylamine (50 mmol), ethanol (50 mmol), and anhydrous tetrahydrofuran (200 mL) were placed in a three-necked round-bottom flask and stirred at 900 rpm. 2-chloro-2-oxo-1,3,2-dioxophosphonane (COP) (100 mmol) was slowly added dropwise at 0 °C for 10 h. The reaction mixture was then stirred at room temperature for 10 h. The reaction mixture was then filtered and washed with a 1:5 mixture of diethyl ether and n-hexane, followed by rotary evaporation; the product was weighed. Next, ethyl 2-(dimethylamino)acrylate (DMAEA) (50 mmol) and 200 mg of 4-methoxyphenol were added, and the mixture was stirred at 70 °C and 900 rpm for 2 days, followed by stirring at room temperature for another 2 days. The reaction mixture was precipitated three times with tetrahydrofuran to remove impurities, and the resulting pale yellow solution was concentrated in a vacuum furnace to obtain ethyl 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate.

[0077] II. Material Application Performance Experiment

[0078] The material properties and applications of the zwitterionic cyclized copolymers disclosed in this invention are as follows:

[0079] The zwitterionic cyclization copolymer reaction disclosed in this invention has good controllability. By changing the composition ratio of polyethylene glycol diacrylate and 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, the molecular weight and degree of cyclization of the resulting polymers are different, thus obtaining zwitterionic cyclization copolymers with different compositions and degrees of cyclization.

[0080] See Figure 5a and Figure 5b The images are the NMR spectra of the zwitterionic cyclized copolymers prepared in Examples 1 and 2 of this invention after purification.

[0081] This invention also discloses the application of zwitterionic cyclized copolymers in the preparation of injectable hydrogels.

[0082] Amphoteric cyclized copolymers can be cross-linked with thiolated gelatin, thiolated hyaluronic acid, or thiolated collagen to form injectable hydrogels. The preparation method is as follows:

[0083] When zwitterionic cyclized copolymers are mixed with thiolated gelatin, thiolated hyaluronic acid, or thiolated collagen at room temperature, a cross-linking reaction can occur rapidly to generate injectable hydrogels.

[0084] The mass-volume ratio of the zwitterionic cyclized copolymer to thiolated gelatin, thiolated hyaluronic acid, or thiolated collagen is 10%.

[0085] The cross-linking reaction occurs at a temperature of 37°C for less than 1 minute.

[0086] See Figure 6a and 6b The diagram shows an injectable hydrogel sample prepared by crosslinking an amphoteric cyclized copolymer with thiolized gelatin according to the present invention, with the sample before and after gelation. It can be seen that the injectable hydrogel after the crosslinking reaction has a stable physical state and has lost its fluidity.

[0087] Furthermore, the zwitterionic cyclized copolymer disclosed in this invention uses PEGDA575 and MCP-Et as reactive monomers, and CPADB as a chain transfer agent and ACVA as an initiator. All of these components are commonly used raw materials in the biomedical field. Therefore, the zwitterionic cyclized copolymer disclosed in this invention has good biocompatibility and can be used in the fields of drug / protein purification, delivery, single-cell encapsulation, antifouling materials, injectable tissue engineering hydrogel scaffolds, etc.

[0088] Therefore, after dissolving polymers and gelatin of different proportions and concentrations in a culture medium and mixing them thoroughly, the mixture is allowed to stand for a few minutes to form a gel, which is then sterilized by ultraviolet light and alcohol. Human adipose-derived stem cells are then spread onto the hydrogel, see [link to relevant documentation]. Figure 7a 7b cells showed high survival rates, and cell adhesion could be regulated by adjusting the ratio of polymer and gelatin. Therefore, the zwitterionic cyclized copolymer disclosed in this invention has good biocompatibility.

[0089] Different polymers, due to variations in double bond content, will exhibit slightly different gelation times when crosslinking with varying concentrations of thiolated gelatin. However, please refer to [link to relevant documentation]. Figure 8 The gelation time is very fast.

[0090] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A zwitterionic copolymer capable of regulating cell adhesion, characterized in that, It is a copolymer of 2-methacryloyloxyethyl phosphocholine and polyethylene glycol diacrylate, and its structural formula is shown below: In the formula, a=b=3~30, m=5~50, n=5~50; r indicates that the polymer is a random copolymer.

2. The method for preparing the zwitterionic copolymer with controllable cell adhesion as described in claim 1, characterized in that, Includes the following steps: 1) Dissolve polyethylene glycol diacrylate, 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, initiator and chain transfer agent in solvent to obtain a mixed solution; The initiator is 4,4'-azobis(4-cyanopentanoic acid) or 2,2′-azo(2-methylpropionitrile); the chain transfer agent is 2-(dodecyltrithiocarbonate)-2-methylpropionic acid, 4-cyano-4-(phenylcarbonylthio)pentanoic acid, 4-cyano-4-[(dodecylthioalkylthiocarbonyl)thioalkyl]pentanoic acid, bis(dodecylthioalkylthiocarbonyl) disulfide, 2-phenyl-2-propylbenzodisulfide or 2-cyano-2-propylbenzodisulfide; the reaction molar ratio of polyethylene glycol diacrylate, 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate, chain transfer agent and initiator is 1:(0.01-1000):(0.0001-0.01):(0.00005-0.005); 2) The mixed solution was subjected to a reversible addition-fragmentation chain transfer radical polymerization reaction under anaerobic conditions, and the reaction process was monitored in real time. When the molecular weight of the reaction reached 1,000 to 100,000 Da, the reaction was stopped, and the reaction solution was purified to obtain a zwitterionic copolymer that can regulate cell adhesion.

3. The method for preparing the zwitterionic copolymer with controllable cell adhesion according to claim 2, characterized in that, In step 2), the temperature of the reversible addition-fragmentation chain transfer radical polymerization reaction is 50~100 ℃.

4. The method for preparing the zwitterionic copolymer with controllable cell adhesion according to claim 2, characterized in that, In step 2), the anaerobic conditions are carried out under an argon atmosphere; real-time monitoring is performed by gel permeation chromatography; the purification of the reaction solution involves precipitating the reaction solution three times with diethyl ether or a mixture of diethyl ether and n-hexane to obtain the reaction product, a zwitterionic copolymer that can regulate cell adhesion.

5. The method for preparing the zwitterionic copolymer with controllable cell adhesion according to claim 2, characterized in that, The 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate used was prepared by the following method: First, triethylamine, ethanol, and anhydrous tetrahydrofuran were thoroughly stirred until homogeneous. 2-chloro-2-oxo-1,3,2-dioxophosphoric acid cycloalkane was added dropwise to the mixture at 0°C. The reaction mixture was then stirred at room temperature for 10 h. After filtration, the reaction mixture was washed with 1:1 diethyl ether and n-hexane, and the product was obtained by rotary evaporation. 2-(dimethylamino)acrylate and 4-methoxyphenol were added to the product, and the mixture was reacted for 6 days under heating and stirring conditions. The reaction mixture was precipitated three times with tetrahydrofuran to remove impurities. The resulting pale yellow solution was concentrated in a vacuum furnace to obtain 2-[2-(acryloylethyl)dimethylamino]ethyl phosphate.

6. A zwitterionic cyclized polymer hydrogel capable of regulating cell adhesion, characterized in that, It is prepared by mixing the zwitterionic copolymer with controllable cell adhesion as described in claim 1 with a thiolized crosslinking agent; wherein: The thiol crosslinking agent is thiolized gelatin, thiolized hyaluronic acid, or thiolized collagen; The mass ratio of the zwitterionic copolymer and the crosslinking agent that can regulate cell adhesion is (0.1-1):(0.01-10).

7. The application of the zwitterionic copolymer with adjustable cell adhesion as described in claim 1 or the zwitterionic cyclized polymer hydrogel with adjustable cell adhesion as described in claim 6 in the preparation of biomedical materials.

8. The application as described in claim 7, characterized in that, The biomedical materials include cell culture materials, antibacterial materials, or injectable tissue-engineered hydrogel scaffolds.

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