CN112169012B - Self-repairable hot-melt biomedical adhesive and preparation method thereof - Google Patents
Self-repairable hot-melt biomedical adhesive and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3324—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof cyclic
- C08G65/3326—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof cyclic aromatic
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G75/00—Macromolecular compounds obtained by reactions forming a linkage containing sulfur with or without nitrogen, oxygen, or carbon in the main chain of the macromolecule
- C08G75/02—Polythioethers
- C08G75/04—Polythioethers from mercapto compounds or metallic derivatives thereof
- C08G75/045—Polythioethers from mercapto compounds or metallic derivatives thereof from mercapto compounds and unsaturated compounds
Abstract
The invention provides a self-repairable hot-melt biomedical adhesive and a preparation method thereof, belonging to the field of biomedical materials. The adhesive is prepared by directly mixing the thiol-terminated hyperbranched polymer which is liquid at room temperature and the aldehyde-terminated polyethylene glycol. The solventless adhesive has higher mechanical properties than the hydrogel adhesive; the adhesive contains a large number of aldehyde groups, so that covalent bonds can be formed with the surface of the tissue, and the adhesive has high tissue binding power; the aldehyde-thiol reversible addition reaction between the two components crosslinks to form a dynamic polymer network, giving the adhesive self-healing, thermoplastic, and thermally detachable capabilities. The adhesive is heated to melt into liquid and re-solidify after cooling. This property allows the adhesive to be used as a hot melt adhesive. The adhesive prepared by the invention has the advantages of simple use method, good adhesion effect, low cytotoxicity and self-repairing performance, and has good application prospect as a biomedical adhesive.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a self-repairable hot-melt biomedical adhesive and a preparation method thereof.
Background
The biomedical adhesive is a biomedical material which is expected to replace surgical suture lines. Compared with the traditional operation suture line, the biomedical adhesive fixes the torn tissues together in a surface bonding mode, thereby achieving the purpose of closing the wound. The biomedical adhesive is convenient to use, cannot cause secondary damage to the damaged part, avoids the generation of scar tissues and has excellent beautifying effect. However, the biomedical cyanoacrylate adhesives commonly used in the market at home and abroad have cytotoxicity, and the adhesive force of fibrin glue and polyethylene glycol adhesives is poor. Therefore, the current biomedical adhesives have a limited clinical application range. The development of biomedical adhesives with excellent properties has been a focus of researchers.
The ideal biomedical adhesive should be liquid prior to use to facilitate administration by injection, and then cure in the appropriate time without harming the surrounding tissue. To meet these requirements, current biomedical adhesives are typically aqueous solutions of polymers, which then bond tissues together by two-component hybrid crosslinking or stimulus-triggered polymer crosslinking. The adhesion of such adhesives arises from two aspects: one is the interfacial interaction between the adhesive and the tissue surface (adhesion); one is the mechanical properties (cohesion) of the adhesive matrix. Interfacial adhesion results from chain entanglement, electrostatic interactions, covalent bonds, etc. of the adhesive with the formation of proteins on the tissue surface. NHS active ester, aldehyde, isocyanate, thiol or catechol active group can be reacted with-NH on tissue surface2The groups such as-SH form chemical bonds, thereby resulting in high interfacial adhesion. In recent years, there is a current trend of research to develop biomedical adhesives with additional functions (antibacterial, drug-loaded, self-healing, etc.). In particular, the dynamic cross-linked network, which is formed by reversible non-covalent bonds or dynamic covalent bonds, imparts self-healing, shape-conforming, and even on-demand dissociation capabilities to the adhesive. However, due to the inherent instability and high water content of the dynamic network, such multifunctional hydrogel adhesives often have poor mechanical properties, thus resulting in low adhesive strength. The introduction of another stable interpenetrating network can enhance the mechanical properties of the dynamic hydrogel, but this adds complexity to the use of the adhesive and results in the adhesive losing functionality. It remains a challenge to develop a self-healing hot melt adhesive with high adhesion using a simple and efficient process.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides a self-repairable hot-melt biomedical adhesive and a preparation method thereof.
As one aspect of the present invention, the present invention provides a technical solution: a preparation method of a self-repairable hot-melt biomedical adhesive comprises the following steps:
step 1: dissolving trifunctional thiol monomers in organic solvent, N2Bubbling for 30min to remove air in the solution, adding difunctional (methyl) acrylate monomer, and reacting the solution in N2Reacting for 24 hours at 40 ℃ under protection, and purifying reaction liquid after the reaction is finished to obtain a thiol-terminated hyperbranched polymer with the molecular weight of 5-80 kDa; the use of polymers with molecular weights below 5kDa or above 80kDa to construct binders is disadvantageous for forming solid binders.
Step 2: dissolving polyethylene glycol, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 4-dimethylaminopyridine in N 'N dimethylformamide, dropwise adding an N' N dimethylformamide solution of p-aldehyde benzoic acid into the solution, and reacting at room temperature for 24 hours; after the reaction is finished, distilling under reduced pressure to remove DMF; the product was dissolved with dichloromethane and washed three times with saturated brine; collecting a dichloromethane layer, dropwise adding the dichloromethane layer into a precipitator formed by diethyl ether and petroleum ether, standing, removing an upper layer solution, and performing vacuum drying to obtain an orange liquid, namely aldehyde group functionalized polyethylene glycol with the molecular weight of 500-1000 Da;
and step 3: mixing the hyperbranched polymer obtained in the step (1) with the aldehyde group functionalized polyethylene glycol obtained in the step (2), stirring for 5min, and curing at room temperature for 1 hour to obtain an adhesive;
wherein the trifunctional thiol monomer in step 1 is trimethylolpropane tris (3-mercaptopropionate), and the difunctional (meth) acrylate monomer is 2- (acryloyloxy) -ethyl methacrylate, 3- (acryloyloxy) -propyl methacrylate, 4- (acryloyloxy) -butyl methacrylate, or 3- (acryloyloxy) -2-hydroxypropyl methacrylate.
Further, the organic solvent described in step 1 is N' N-dimethylformamide, dioxane, acetonitrile or tetrahydrofuran.
Further, in the step 1, the concentration of the trifunctional thiol monomer is 0.1-0.5 g/mL, the concentration of the difunctional (methyl) acrylate monomer is 0.05-0.4 g/mL, and the molar ratio of the trifunctional thiol monomer to the difunctional (methyl) acrylate monomer is 1: 0.7-1.
Further, the purification reaction in step 1 specifically comprises:
(1) concentrating the reaction solution by rotary evaporation, and then precipitating in anhydrous ether;
(2) re-dissolving with dichloromethane, and precipitating in anhydrous ether;
(3) and (3) repeating the step (2) for 3 times, and then drying the precipitate in vacuum to obtain the hyperbranched polymer.
Further, the total concentration of the NN dimethylformamide solution of the polyethylene glycol, the p-aldehyde benzoic acid and the 4-dimethylaminopyridine in the step 2 is 0.2-0.5 g/mL; the concentration of the 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride in DMF is 0.05-0.1 g/mL.
Further, the volume ratio of the petroleum ether to the diethyl ether in the precipitation liquid in the step 2 is 1: 1-4.
Further, the ratio of the hyperbranched polymer to the aldehyde-group functionalized polyethylene glycol in the step 3 is 1: 0.5-1.5 in terms of thiol functional groups and aldehyde-group functional groups.
As another aspect of the invention, the invention also provides a peelable biomedical adhesive prepared by the preparation method of the self-repairable hot-melt biomedical adhesive.
The invention has the beneficial effects that:
1. the adhesive provided by the invention is prepared by directly mixing a hyperbranched polymer with a terminal thiol group and aldehyde-terminated polyethylene glycol without adding a solvent. Solvent-free adhesives have higher mechanical properties and adhesive strength than hydrogel adhesives.
2. The aldehyde groups and the thiol reversibly undergo an addition reaction to form a dynamic polymer network, which imparts self-healing, shape-conforming, and even on-demand dissociation capabilities to the adhesive.
3. The adhesive contains a large number of aldehyde groups, so that covalent bonds can be formed with the surface of the tissue, and the adhesive has high tissue binding force.
4. The adhesive is heated and melted into liquid, and is solidified again after being cooled, so that the functions of stripping and repeated adhesion are realized, the property enables the adhesive to be used as hot melt adhesive, and the method is simple and quick.
Drawings
FIG. 1 is a diagram of an aldehyde-thiol reversible addition reaction between binder components.
FIG. 2 is a schematic diagram of the adhesive preparation process of example 1.
FIG. 3 is a dynamic frequency sweep test curve of the adhesive of example 1 after 1h of room temperature cure.
FIG. 4 is a graph of the storage modulus of the adhesives of examples 1-5 after 1h of curing at room temperature.
FIG. 5 is a plot of the change in storage modulus and loss modulus at programmed temperatures in the temperature range of 25 deg.C to 80 deg.C for the adhesive of example 1.
FIG. 6 is a plot of the change in storage modulus and loss modulus for the adhesives of example 1 over a temperature range of 25 deg.C to 80 deg.C.
FIG. 7 is a graph showing the transition temperature of the adhesive according to the content of the aldehyde-based functionalized polyethylene glycol in examples 1 to 5.
FIG. 8 is a graph of the bond strength of the adhesives of examples 1-5 to pigskin.
FIG. 9 is a self-healing efficiency curve for the adhesive of example 1.
FIG. 10 is a graph showing the adhesive strength of the adhesive of example 1 at repeated temperatures of 60 ℃ and 25 ℃.
FIG. 11 shows the cell viability of the adhesives of examples 1-5 for L929 cells at 24 hours and 48 hours.
Detailed Description
Example 1
Step 2, 40g of polyethylene glycol, 22g of p-aldehyde benzoic acid and 0.82g of 4-dimethylaminopyridine were weighed out and dissolved in 150mL of N' -N-dimethylformamide. 24.2g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride was weighed and dissolved in 400mL of N' N-dimethylformamide, and then added dropwise to the solution and reacted at room temperature for 24 hours. After completion of the reaction, DMF was distilled off under reduced pressure, and then dissolved in 100mL of methylene chloride and washed three times with saturated brine. Collecting dichloromethane layer, dripping into 1000mL mixed solution of petroleum ether/diethyl ether at volume ratio of 1: 1, precipitating, and vacuum drying to obtain yellow aldehyde group functionalized polyethylene glycol with molecular weight of about 1000Da, and recording as PEGCHO.
And 3, mixing aldehyde-functionalized polyethylene glycol (PEGCHO, 1mol based on aldehyde functional groups) and hyperbranched polymer (HBP, 1mol based on thiol functional groups), stirring for 5min, and curing at room temperature for 1h to obtain the adhesive, wherein the adhesive is named as 1-1, and aldehyde-thiol reversible addition reaction among adhesive components is shown in figure 1.
Example 2
The same procedure as in example 1, except for changing the amount of the aldehyde-functionalized polyethylene glycol (PEGCHO, 0.5mol based on the aldehyde functional group) added in step 3, gave a binder, which was named 1 to 0.5.
Example 3
The same procedure as in example 1, except for changing the amount of the aldehyde-functionalized polyethylene glycol (PEGCHO, 0.75mol based on the aldehyde functional group) added in step 3, gave a binder, which was designated 1 to 0.75.
Example 4
The same procedure as in example 1, except for changing the amount of the aldehyde-functionalized polyethylene glycol (PEGCHO, 1.25mol based on the aldehyde functional group) added in step 3, gave a binder, which was designated 1 to 1.25.
Example 5
The same procedure as in example 1, except for changing the amount of the aldehyde-functionalized polyethylene glycol (PEG-NCO, 1.5mol based on the aldehyde functional group) added in step 3, gave a binder, which was designated 1 to 1.5.
FIG. 1 is a schematic representation of the preparation of the adhesive of example 1. As shown in fig. 2, the hyperbranched polymer is a viscous fluid at room temperature, and is stirred for 5min after the aldehyde-functionalized polyethylene glycol is added to form a viscoelastic adhesive. The adhesive behaves as a solid at room temperature, but melts to a liquid upon heating.
Example 6 test method
1. Rheological Properties of biomedical Adhesives test:
the binders of examples 1-5 were added to respective tetrafluoroethylene molds and cured to form disks 1cm in diameter and 1mm in thickness. A rotary rheometer adopts an oscillation mode, takes 1% strain rate, and tests the storage modulus (G ') and the loss modulus (G') of the glue with the corresponding formula after being cured for 1 hour at room temperature in a strain frequency range from 0.1Hz to 100 Hz.
FIG. 3 is a dynamic frequency sweep test curve of the adhesive of example 1 after 1h of room temperature cure. As shown in FIG. 3, the adhesive exhibits liquid characteristics at low frequencies (G '> G') and solid characteristics at high frequencies (G '< G'); this is a typical property of dynamic networks. FIG. 4 is a graph of the storage modulus of the adhesives of examples 1-5 after 1h of curing at room temperature. As shown in FIG. 4, the solvent-free adhesive prepared according to the present invention has a higher storage modulus (45kPa to 100kPa) compared to dynamic polymeric hydrogel materials (storage modulus is typically less than 1 kPa). The crosslinking density of the adhesive can be adjusted by controlling the proportion of the hyperbranched polymer and the aldehyde functional polyethylene glycol, so that the storage modulus of the adhesive is controlled. The modulus of the adhesive matches the shear modulus of human soft tissue (skin about 100kPa, stomach 8-45kPa, ventricular wall 60-148kPa, liver 37-340 kPa). This consistent mechanical properties allows the adhesive to conform to the deformation of human tissue, avoiding stress concentrations at the base of the adhesive and alleviating patient discomfort.
2. Thermo-rheological testing of biomedical adhesives:
the binders of examples 1-5 were added to respective tetrafluoroethylene molds and cured to form disks 1cm in diameter and 1mm in thickness. The adhesive was scanned for storage modulus and loss modulus changes at 25-80 ℃ using a rotational rheometer in an oscillatory mode at a strain rate of 1% and a strain frequency of 1 Hz.
Fig. 5 and 6 are plots of the change in storage modulus and loss modulus for the adhesives of example 1 over the temperature range of 25 c to 80 c. The storage and loss moduli of the adhesive in the solid state after heating decrease rapidly with temperature, the adhesive exhibiting a transition from the solid state character (G '< G') to the liquid character (G '> G'); but also returns to the original modulus as the temperature decreases. This indicates that the dynamic binder network reversibly collapses-rebuilds upon heating and cooling. The temperature at which the G 'curve and the G' curve intersect in FIGS. 5 and 6 is recorded as the transition temperature. FIG. 7 is a graph showing the behavior of the transition temperature of the adhesive according to the content of the aldehyde-based functionalized polyethylene glycol in examples 1 to 5. The higher the content of aldehyde-group functionalized polyethylene glycol, the lower the transition temperature.
3. Adhesion performance testing of biomedical adhesives:
the adhesives of examples 1-5 were tested for adhesion using hairless pigskin as the biological substrate. Fresh pigskin was purchased from a local supermarket and processed according to astm f2255-2015 international standard and cut into strips of 2.5cm x 5 cm. And wiping the surface of the pigskin with isopropanol and water in sequence to remove residual grease on the pigskin, wiping the pigskin to obtain a pigskin strip for testing, and inspecting the caking property of the adhesive by a stretching lap joint shearing test method. The prepared adhesive was heated to melt it and then applied to one end of the leather strip. The two strips were lapped together, pressed against the bonding area with a 100g weight and bonded for 1 hour at room temperature. Similarly, the currently commercially available fibrin glue adhesive was used directly as a control group. The maximum adhesion force F was measured by a tensile test at a tensile rate of 5mm/min, and the adhesive strength of the adhesive was calculated by the following formula, in which at least 5 samples were set for each sample in each set of the above experiments, and the experimental data were expressed by the mean value ± standard deviation.
FIG. 8 is a graph of the bond strength of the adhesives of examples 1-5 to pigskin. As shown in FIG. 8, the content of the HBP-PEGCHO adhesive is related to the content of aldehyde group functionalized polyethylene glycol, and the HBP-PEGCHO adhesive can reach about 54kPa and is far greater than the adhesive strength (5-20 kPa) reported by a commercial fibrin glue adhesive. The adhesive prepared by the invention contains a large amount of aldehyde groups, and can generate covalent bonds with the tissue surface, so that the adhesive has higher adhesiveness.
4. Self-repair performance test of biomedical adhesive:
the self-healing performance of the adhesive of example 1 was tested on stainless steel as a substrate. A2.5 cm by 5cm stainless steel sheet was taken. And (3) cleaning the surface of the stainless steel by using ethanol and water in sequence, and drying to obtain the base material required by the experiment. The prepared adhesive was heated to melt it and then applied to one end of the leather strip. The two stainless steel sheets were lapped together, and the bonded area was fixed with a dovetail clip and bonded at room temperature for 1 hour. The adhesive was then tested for adhesive strength. The tested adhesives were re-lapped together, secured for different times using dovetail clips, and then tested for adhesive strength for different times of repair. The self-healing efficiency of the adhesive was calculated by the following formula:
FIG. 9 is a self-healing efficiency curve for the adhesive of example 1. As shown in fig. 9, the adhesive after fracture was rebonded after lapping and gradually reached the initial bond strength before fracture after 2 hours. The adhesive prepared by the invention is composed of thiol-aldehyde group dynamic addition chemistry, and reversible addition fragmentation of thiol-aldehyde enables the fractured adhesive matrixes to be recombined together, thereby showing self-repairing performance.
5. Repeated adhesion reversibility test for biomedical adhesives
The adhesive of example 1 was tested for adhesive strength at different temperatures using stainless steel as a substrate. The adhesive strength of the adhesive at 60 ℃ and 25 ℃ is repeatedly measured in sequence by taking the adhesive sample overlapped by the stainless steel.
FIG. 10 is a graph showing the adhesive strength of the adhesive in example 1 at 60 ℃ and 25 ℃ under repeated adhesion reversibility. The adhesive melts to a liquid at 60 ℃ and loses cohesion, while resolidifying to a solid matrix at 25 ℃ exhibiting high adhesive strength (-90 kPa). This process was repeated reversibly, indicating that the adhesive has the ability to be thermally disassembled and bonded repeatedly.
6. Cytotoxicity testing of biomedical adhesives:
the adhesives of each formula are respectively immersed into a complete culture medium for culturing for two days after being subjected to ultraviolet irradiation and aseptic treatment, so as to prepare a leaching solution culture medium, wherein the ratio of the culture medium to the adhesives is 0.2 g/ml. The cytotoxicity of the adhesive was tested with mouse fibroblasts (L929 cells) as the study subjects. L929 cells in logarithmic growth phase were seeded in 96-well cell culture plates at 37 ℃ and 95% relative humidity in 5% CO2The cell culture box of (2) is cultured for 24 hours. After the adhesion is completely realized, the L929 cells are cultured for 24 hours and 48 hours respectively by using the leaching culture medium of the adhesive. For comparison, the control group did not have an adhesive sample. After 24h or 48h of culture, 100 mu L of 5mg/mL 3- (4, 5-dimethylthiazole-2) -2, 5-diphenyl tetrazolium bromide solution is added into each hole respectively for cell activity test. After further culturing for 4 hours, the mixed medium was aspirated, and then 500. mu.L of dimethyl sulfoxide was added and dissolved for 10min with shaking. Then, the absorbance value (namely, OD value) of the solution at 570nm is measured by a microplate reader, and the relative activity of the cells of the experimental group is calculated by the following formula:
FIG. 11 shows the cell viability of the adhesives of examples 1-5 for L929 cells at 24 hours and 48 hours. As shown in FIG. 11, the cytotoxicity of the adhesive was related to the content of aldehyde-functionalized polyethylene glycol when L929 cells were cultured with the adhesive for 24h and 48 h. The relative cell survival rates of the adhesives with lower aldehyde functional polyethylene glycol content in the experimental groups are all over 80 percent, while the relative cell survival rates of the adhesives with higher aldehyde functional polyethylene glycol content in the experimental groups 1-1.25 and 1-1.5 are respectively 74 percent and 39 percent in 24 hours and 64 percent and 29 percent in 48 hours. The adhesive with lower content of aldehyde group functionalized polyethylene glycol shows low cytotoxicity and high cell survival rate, and can be used as biomedical materials.
Claims (8)
1. A preparation method of a self-repairable hot-melt biomedical adhesive is characterized by comprising the following steps:
step 1: dissolving trifunctional thiol monomers in organic solvent, N2Bubbling for 30min to remove air in the solution, adding difunctional (methyl) acrylate monomer, and reacting the solution in N2Reacting for 24 hours at 40 ℃ under protection, and purifying reaction liquid after the reaction is finished to obtain a thiol-terminated hyperbranched polymer with the molecular weight of 5-80 kDa;
step 2: dissolving polyethylene glycol, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 4-dimethylaminopyridine in N' -N dimethylformamide DMF, dropwise adding a DMF solution of p-aldehyde benzoic acid into the solution, and reacting at room temperature for 24 hours; after the reaction is finished, distilling under reduced pressure to remove DMF; the product was dissolved with dichloromethane and washed with saturated brine; collecting a dichloromethane layer, dropwise adding the dichloromethane layer into a precipitation solution formed by diethyl ether and petroleum ether, standing, removing an upper layer solution, and performing vacuum drying to obtain an orange liquid, namely aldehyde group functionalized polyethylene glycol with the molecular weight of 500-1000 Da;
and step 3: mixing the hyperbranched polymer obtained in the step (1) and the aldehyde group functionalized polyethylene glycol obtained in the step (2) according to a certain proportion, stirring, and curing at room temperature to obtain an adhesive;
wherein the trifunctional thiol monomer is trimethylolpropane tris (3-mercaptopropionate); the difunctional (meth) acrylate monomer is 2- (acryloyloxy) -ethyl methacrylate, 3- (acryloyloxy) -propyl methacrylate, 4- (acryloyloxy) -butyl methacrylate or 3- (acryloyloxy) -2-hydroxypropyl methacrylate.
2. The preparation method of the self-repairable hot-melt biomedical adhesive according to claim 1, wherein the organic solvent in step 1 is N' N-dimethylformamide, dioxane, acetonitrile or tetrahydrofuran.
3. The preparation method of the self-repairable hot-melt biomedical adhesive as claimed in claim 1, wherein in the step 1, the concentration of the trifunctional thiol monomer is 0.1-0.5 g/mL, the concentration of the difunctional (meth) acrylate monomer is 0.05-0.4 g/mL, and the molar ratio of the trifunctional thiol monomer to the difunctional (meth) acrylate monomer is 1: 0.7-1.
4. The preparation method of the self-repairable hot-melt biomedical adhesive according to claim 1, wherein the purification reaction in step 1 specifically comprises:
(1) concentrating the reaction solution by rotary evaporation, and then precipitating in anhydrous ether;
(2) re-dissolving with dichloromethane, and precipitating in anhydrous ether;
(3) and (3) repeating the step (2) for a plurality of times, and then drying the precipitate in vacuum to obtain the hyperbranched polymer.
5. The preparation method of the self-repairable hot-melt biomedical adhesive according to claim 1, characterized in that the overall concentration of the DMF solution of the polyethylene glycol, the p-aldehyde benzoic acid and the 4-dimethylaminopyridine in the step 2 is 0.2-0.5 g/mL; the concentration of the 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride in DMF is 0.05-0.1 g/mL.
6. The preparation method of the self-repairable hot-melt biomedical adhesive as claimed in claim 1, wherein the volume ratio of petroleum ether to diethyl ether in the precipitation liquid in the step 2 is 1: 1-4.
7. The preparation method of the self-repairable hot-melt biomedical adhesive according to claim 1, wherein the ratio of the hyperbranched polymer to the aldehyde-functionalized polyethylene glycol in the step 3 is 1: 0.5-1.5 in terms of thiol functional groups and aldehyde functional groups.
8. The self-repairable hot-melt biomedical adhesive is characterized by being prepared by the preparation method of the self-repairable hot-melt biomedical adhesive.
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