CN111675789B - Polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel and preparation - Google Patents
Polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel and preparation Download PDFInfo
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Abstract
The invention belongs to the technical field of biological high polymer materials, and discloses polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel and a preparation method and application thereof. The method comprises the steps of firstly adding heparin and dopamine into water for mixing, and adjusting an alkaline oxygen-containing environment to pre-polymerize the dopamine to obtain a PDA-HP compound; then sequentially adding acrylamide and 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, and carrying out free radical polymerization under the action of an initiator and a cross-linking agent to obtain the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel. The dopamine pre-polymerization reaction time is short, excessive oxidation of dopamine is avoided, enough free phenolic hydroxyl groups are kept in the hydrogel, and the hydrogel has strong tissue adhesion and good cell affinity. The hydrogel prepared by the method has excellent mechanical property, self-adhesion property and antibacterial property, has good biocompatibility, and can be widely applied to the field of biomedical materials.
Description
Technical Field
The invention belongs to the technical field of biological high polymer materials, and particularly relates to polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel and a preparation method and application thereof.
Background
The skin, the largest, outermost exposed organ of the human body, is extremely vulnerable to various traumas. Various kinds of acute and chronic wounds puzzle people for hundreds of years, so that the method is a research hotspot in the medical field. The burns or scalds are easy to cause large-area skin injuries of different degrees, and patients often suffer shock and even death due to body fluid loss and infection, which are the difficulties of the current clinical treatment.
The hydrogel is a three-dimensional network structure material formed by crosslinking hydrophilic macromolecules or polymers by means of hydrogen bonds, covalent bonds or van der waals force and other acting forces. The hydrogel has similar structure and characteristics with human soft tissue, has the advantages of maintaining moist wound healing environment, absorbing exudate, ventilating, cooling wound, relieving pain and the like, and is widely applied to wound dressings. The proper hydrogel dressing can well replace damaged skin tissues, plays a role in shielding infection of bacteria or other external substances, and provides a good environment for wound healing. Chronic wounds infected with bacteria and other microorganisms are one of the major factors leading to complications, and development of hydrogel dressings having antibacterial properties is an effective method for improving wound healing efficiency, and in recent years, antibacterial hydrogels have received much attention from researchers.
Generally, the antibacterial hydrogel takes hydrogel as a carrier to load antibacterial drugs or silver nanoparticles. Abuse of antibacterial drugs can cause problems with drug resistance, and the biological safety of silver ions has been problematic. Most of the existing antibacterial hydrogels are designed only by considering biocompatibility and basic mechanical properties, and have many other problems such as: the problems of overhigh preparation cost, fussy preparation flow, overhigh reaction condition and the like can not comprehensively treat the wound.
Therefore, the intrinsic antibacterial hydrogel material with bulk uniformity is formed by chemically crosslinking or physically crosslinking the monomers with antibacterial performance, and the antibacterial performance can be exerted more stably and durably. Meanwhile, the antibacterial hydrogel which has multiple functions, can comprehensively treat the wound problem and has good biocompatibility is urgently needed to be further researched, the problems are integrally solved, and the antibacterial hydrogel is applied to clinical treatment as soon as possible.
Disclosure of Invention
In order to overcome the disadvantages and shortcomings of the prior art, the first objective of the present invention is to provide a method for preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
The invention also aims to provide the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared by the method.
The invention further aims to provide application of the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel in the field of biomedical materials.
The purpose of the invention is realized by the following scheme:
a preparation method of polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel comprises the steps of adding Heparin (HP) and Dopamine (DA) into water, mixing, adjusting an alkaline oxygen-containing environment to pre-polymerize the dopamine to obtain a PDA-HP compound; and sequentially adding Acrylamide (AM) and 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt (AEDMHA), and carrying out free radical polymerization under the action of an initiator and a cross-linking agent to obtain the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel (PDA-HP-AEDMHA-PAM).
The mass ratio of the heparin, the dopamine, the acrylamide and the 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt is preferably (5-20): 1-3): 50-500): 5-30), more preferably (10-15): 1-2): 100-300): 10-20.
The concentration of heparin in water is preferably 10-20 mg/mL.
The prepolymerization time may be from 0.2 to 2 hours, more preferably from 0.2 to 1 hour.
The alkalinity is preferably in the range of 9 to 12. The system can be adjusted to be alkaline by adding a sodium hydroxide solution, and more preferably, the system is adjusted by using a sodium hydroxide solution having a concentration of 1 mol/L.
The oxygen-containing environment can be achieved by stirring at room temperature.
Preferably, the heparin and the dopamine are added into the water and stirred to be dissolved, and then the dopamine is added and stirred to be dissolved.
The initiator may be an initiator conventionally used in polymerization, such as ammonium persulfate, potassium persulfate, sodium persulfate, etc., and more preferably ammonium persulfate is used as the initiator. The mass ratio of the initiator to the acrylamide is preferably 0.01:1-0.02:1, more preferably 0.016: 1.
The cross-linking agent can be a cross-linking agent which is conventionally used in polymerization reaction, such as N, N-methylene bisacrylamide, polyethylene glycol diacrylate and dicumyl peroxide, and the N, N-methylene bisacrylamide is more preferably used as the cross-linking agent. The mass ratio of the cross-linking agent to the acrylamide is preferably 0.01:1 to 0.03:1, and more preferably 0.012: 1.
When an initiator is used, an initiator aid such as tetramethylethylenediamine or the like may be added. The amount of the initiation aid used is preferably 0.1 to 0.5%, more preferably 0.2%, of the total volume of the reaction system.
The initiator and the cross-linking agent are preferably uniformly stirred after being added into the system, and more preferably stirred for 1-5 min.
After the initiator and the cross-linking agent are added, a solution system is subjected to free radical polymerization reaction to generate the PDA-HP-AEDMHA-PAM hydrogel.
The method of the invention may specifically comprise the steps of:
(1) adding heparin into water, stirring and dissolving, adding dopamine into the solution, stirring and dissolving to form a DA-HP compound, adjusting the pH of the system to 9-12 by using a NaOH solution, and stirring at room temperature for 0.2-1h to pre-polymerize DA to form a PDA-HP compound;
(2) adding acrylamide into the PDA-HP compound solution obtained in the step (1), then adding 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, adding an initiator, a cross-linking agent and an initiation aid, uniformly stirring, and carrying out free radical polymerization reaction on the system to generate the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
The preparation method of the invention firstly stirs dopamine and heparin to form dopamine-heparin compound, induces dopamine to polymerize in alkaline oxygen-containing environment to form polydopamine, has short prepolymerization reaction time, avoids excessive oxidation of dopamine, keeps enough free phenolic hydroxyl in hydrogel, and ensures that the hydrogel has stronger tissue adhesion and good cell affinity. Then adding acrylamide and 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt into the polydopamine-heparin solution, and then carrying out free radical polymerization under the action of an initiator and a cross-linking agent to form the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
The invention also provides polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared by the method, which has excellent mechanical property, self-adhesion property and antibacterial property, has good biocompatibility and can be widely applied to the field of biomedical materials.
Compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the preparation method has the advantages of mild reaction conditions, short preparation time, simple operation and easy control.
(2) The invention has rich raw material sources and low cost.
(3) The invention constructs novel composite antibacterial hydrogel integrating various functional components by a free radical copolymerization mode, namely functional hydrogel integrating mechanical property, self-adhesion and antibacterial property.
(4) The polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared by the invention has good biocompatibility and wide application prospect of biomedical materials.
Drawings
FIG. 1 is a microscopic scanning electron microscope image of the cross section of the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared in example 1 after freeze drying.
FIG. 2 is a graph of compressive stress-strain for the polydopamine/polyacrylamide hydrogel (PDA-PAM), polydopamine-heparin/polyacrylamide hydrogel (PDA-HP-PAM), and polydopamine-heparin/quaternary ammonium salt/polyacrylamide (PDA-HP-AEDMHA-PAM) hydrogels prepared in example 4.
FIG. 3 is a graph showing swelling ratios of polydopamine/polyacrylamide hydrogel (PDA-PAM), polydopamine-heparin/polyacrylamide hydrogel (PDA-HP-PAM), and polydopamine-heparin/quaternary ammonium salt/polyacrylamide (PDA-HP-AEDMHA-PAM) hydrogels prepared in example 4.
Fig. 4 is a graph showing the antibacterial effects of the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel (PDA-HP-AEDMHA-PAM) prepared in example 5 on escherichia coli (e.coil) and staphylococcus aureus (s.aureus). Wherein (a) is polyacrylamide hydrogel (PAM); (b) is polydopamine/polyacrylamide hydrogel (PDA-PAM); (c) is polydopamine-heparin/polyacrylamide hydrogel (PDA-HP-PAM); (d) is polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel (PDA-HP-AEDMHA-PAM).
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto. The materials referred to in the following examples are commercially available. In the examples, the components are used in g and mL in parts by mass.
Example 1
(1) Weighing 13 parts by mass of heparin, adding the heparin into 1000 parts by volume of water, stirring and dissolving, adding 1 part by mass of dopamine into an HP solution, stirring and dissolving to form a DA-HP compound, adjusting the pH value of a solution system to 11 by using 1mol/L NaOH, stirring at room temperature for 0.5h, and carrying out DA prepolymerization under an alkaline oxygen-containing environment to form the PDA-HP compound.
(2) Weighing 250 parts by mass of acrylamide, adding the acrylamide into the PDA-HP compound solution system in the step (1), then adding 20 parts by mass of 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, then sequentially adding 4 parts by mass of ammonium persulfate, 3 parts by mass of N, N-methylene bisacrylamide and finally adding 2 parts by volume of tetramethyl ethylenediamine, stirring for 3 minutes, stopping, and carrying out free radical polymerization reaction on the solution to generate the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
The polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel obtained is subjected to freeze drying and then is observed by a section scanning electron microscope, and the result is shown in figure 1. As can be seen from FIG. 1, the gel has a porous structure inside, which is beneficial to providing a matrix for the growth of cells and more conveniently conveying nutrients to the cells, so that the cells can grow better.
Example 2
(1) Weighing 10 parts by mass of heparin, adding the heparin into 1000 parts by volume of water, stirring and dissolving, adding 3 parts by mass of dopamine into an HP solution, stirring and dissolving to form a DA-HP compound, adjusting the pH value of a solution system to 11 by using 1mol/L NaOH, stirring at room temperature for 0.2h, and carrying out DA prepolymerization in an alkaline oxygen-containing environment to form the PDA-HP compound.
(2) Weighing 100 parts by mass of acrylamide, adding the acrylamide into the PDA-HP compound solution system in the step (1), then adding 10 parts by mass of 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, then sequentially adding 2.5 parts by mass of ammonium persulfate, 2.5 parts by mass of N, N-methylene bisacrylamide and finally 2 parts by volume of tetramethylethylenediamine, stirring for 3 minutes, stopping, and carrying out free radical polymerization on the solution to generate polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
Example 3
(1) Weighing 20 parts by mass of heparin, adding the heparin into 1000 parts by volume of water, stirring and dissolving, adding 2 parts by mass of dopamine into an HP solution, stirring and dissolving to form a DA-HP compound, adjusting the pH value of a solution system to 11 by using 1mol/L NaOH, stirring for 1 hour at room temperature, and carrying out DA prepolymerization under an alkaline oxygen-containing environment to form the PDA-HP compound.
(2) Weighing 500 parts by mass of acrylamide, adding the acrylamide into the PDA-HP compound solution system in the step (1), then adding 30 parts by mass of 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, then sequentially adding 5 parts by mass of ammonium persulfate, 7.5 parts by mass of N, N-methylene bisacrylamide and finally adding 5 parts by volume of tetramethyl ethylenediamine, stirring for 3 minutes, and stopping, wherein the solution undergoes a free radical polymerization reaction to generate the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
Example 4: mechanical property and swelling property test of polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel
(1) Preparation of polydopamine/polyacrylamide hydrogel
Weighing 0.01 part by mass of dopamine, adding the dopamine into 10 parts by volume of water, stirring and dissolving, adjusting the pH value of a solution system to 11 by using 1mol/L NaOH, stirring at room temperature for 30 minutes, and carrying out prepolymerization on the dopamine in an alkaline oxygen-containing environment to form polydopamine. Weighing 2.5 parts by mass of acrylamide, adding the acrylamide into the solution to terminate the pre-polymerization of DA, sequentially adding 0.04 part by mass of ammonium persulfate, 0.027 part by mass of N, N-methylene bisacrylamide and finally 0.02 part by volume of tetramethylethylenediamine, stirring for 3 minutes, stopping, and carrying out free radical polymerization reaction on the solution to generate polydopamine/polyacrylamide hydrogel (PDA-PAM).
(2) Preparation of polydopamine-heparin/polyacrylamide hydrogel
Weighing 0.13 part by mass of heparin, adding the heparin into 10 parts by volume of water, stirring and dissolving, adding 0.01 part by mass of dopamine into an HP solution, stirring and dissolving to form a DA-HP compound, adjusting the pH value of a solution system to 11 by using 1mol/L NaOH, stirring at room temperature for 30 minutes, and carrying out DA prepolymerization under an alkaline oxygen-containing environment to form the PDA-HP compound. Weighing 2.5 parts by mass of acrylamide, adding the acrylamide into the solution to terminate the pre-polymerization of DA, sequentially adding 0.04 part by mass of ammonium persulfate, 0.027 part by mass of N, N-methylene bisacrylamide and finally 0.02 part by volume of tetramethylethylenediamine, stirring for 3 minutes, stopping, and carrying out free radical polymerization reaction on the solution to generate polydopamine-heparin/polyacrylamide hydrogel (PDA-HP-PAM).
(3) The mechanical property test and the swelling property test were performed on the hydrogel prepared in example 1 and the hydrogels obtained in the above step (1) and step (2):
and (3) testing mechanical properties: three samples with the same size are taken from the three hydrogels respectively, and an electronic universal tester (model number is ELF3220) is used for testing the tensile property of the three hydrogel samples, wherein the compression rate is 2mm/min, and the compression amount of the hydrogel is 60%. Stress-strain plots were taken and the results are shown in FIG. 2. As can be seen from figure 2, the elastic modulus and the compressive modulus of the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared by the method are both stronger than those of other two groups of hydrogels, wherein the compressive modulus can be as high as 56Kpa which is 14 times that of PDA-PAM hydrogel, and 4 times that of PDA-HP-PAM hydrogel. Therefore, the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel disclosed by the invention has excellent mechanical properties and can meet the mechanical property requirements of wound dressings.
Swelling property test: three samples of the same size were taken from each of the three hydrogels and lyophilized. Weighing and recording the original weight of the sample, putting the sample into PBS buffer solution for swelling rate experiment, then placing the sample in a 37 ℃ shaking table for oscillation, taking out the sample at certain intervals, sucking water on the surface of the hydrogel by using filter paper and immediately weighing the sample. Weighing the sample at 0min, 15min, 30min, 45min, 60min, 90min, 120min, 150min, and 180min respectively, and using the formula SR ═ W s -W d )/W d The swelling ratio of the hydrogel was calculated at 100% and plotted as the swelling ratio versus time. Wherein SR: swelling ratio, W d : quality of initial lyophilized hydrogel, W s : hydrogel quality after swelling. The results are shown in FIG. 3. As can be seen from FIG. 3, the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel prepared by the invention is 443.77%, which is 1.29 times that of PDA-PAM hydrogel and 1.07 times that of PDA-HP-PAM hydrogel. Therefore, the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel disclosed by the invention has excellent water absorption and swelling properties, can absorb wound penetrating fluid and meets the requirements of wound dressings.
Example 5: antibacterial performance test of polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel
(1) Preparation of Polyacrylamide hydrogel
Weighing 2.5 parts by mass of acrylamide, adding the acrylamide into 10 parts by volume of water, stirring and dissolving, sequentially adding 0.04 part by mass of ammonium persulfate, 0.027 part by mass of N, N-methylene bisacrylamide and finally adding 0.02 part by volume of tetramethyl ethylenediamine, and carrying out free radical polymerization on the solution to generate polyacrylamide hydrogel (PAM).
(2) Polydopamine/polyacrylamide hydrogel (PDA-PAM) and polydopamine-heparin/polyacrylamide hydrogel (PDA-HP-PAM) were prepared in the same manner as in step (1) and step (2) of example 4.
(3) And (3) carrying out an antibacterial performance test (bacteriostasis ring method) on the hydrogel prepared in the example 1 and the hydrogel obtained in the step (1) and the step (2):
PAM, PDA-PAM and PDA-HP-PAM hydrogel are used as negative control groups, and PDA-HP-AEDMHA-PAM hydrogel is used as an experimental group. Three replicates were set for each negative control and experimental group. The two bacteria used in the test were the gram negative bacteria escherichia coli (e.coil) and the gram positive bacteria staphylococcus aureus (s.aureus). The specific experimental steps are as follows:
(A) preparing LB agar and LB broth according to the proportion;
(B) setting the temperature of the sterilization pot at 121 ℃ and the sterilization time at 20 minutes to carry out damp-heat sterilization on the LB broth and the LB agar; sterilizing four hydrogel samples for three hours under ultraviolet irradiation;
(C) recovering Escherichia coli and Staphylococcus aureus, performing two passages to maintain bacterial activity, respectively preparing bacterial suspension, and diluting to 10% 6 cfu/mL；
(D) 200. mu.L of each bacterial suspension (10. mu.L) was added to each well-prepared and sterilized agar plate 6 cfu/mL), the spreader is evenly spread, then the four hydrogel samples are sequentially placed on the agar plate paved with the bacterial suspension at equal intervals, the mark is made, and the four hydrogel samples are placed in a bacterial incubator at 37 ℃ for culturing for 18 hours;
(E) and taking out after 18 hours, measuring the size of the inhibition zone by using a vernier caliper, and recording and photographing.
The test results are shown in fig. 4. The size of each hydrogel for inhibiting escherichia coli by using the vernier caliper is as follows in sequence: PDA-HP-AEDMHA-PAM (19.3mm) > PDA-HP-PAM (18.44mm) > PDA-PAM (14.52mm) > PAM (12.9mm), all larger than the standard diameter of 7.00 mm; the size of each hydrogel antibacterial zone of staphylococcus aureus measured by the vernier caliper is as follows in sequence: PDA-HP-AEDMHA-PAM (21.48mm) > PDA-HP-PAM (19.02mm) > PDA-PAM (15.6mm) > PAM (13.2mm), all larger than the standard diameter of 7.00 mm. Therefore, the PDA-HP-AEDMHA-PAM hydrogel disclosed by the invention has remarkably excellent antibacterial property.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A preparation method of polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel is characterized in that heparin and dopamine are added into water to be mixed, and an alkaline oxygen-containing environment is adjusted to pre-polymerize the dopamine to obtain a PDA-HP compound; then sequentially adding acrylamide and 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, and carrying out free radical polymerization under the action of an initiator and a cross-linking agent to obtain the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
2. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: the mass ratio of the heparin, the dopamine, the acrylamide and the 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt is (5-20): (1-3): (50-500): (5-30).
3. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: the concentration of the heparin in water is 10-20 mg/mL.
4. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: the prepolymerization time is 0.2-2 h.
5. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: the alkalinity means that the pH is 9-12.
6. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: the initiator comprises at least one of ammonium persulfate, potassium persulfate and sodium persulfate; the cross-linking agent comprises at least one of N, N-methylene bisacrylamide, polyethylene glycol diacrylate and dicumyl peroxide.
7. The method of preparing a polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, wherein: when an initiator is used, an initiation aid is also added.
8. The method for preparing polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 1, characterized in that it comprises the following steps:
(1) adding heparin into water, stirring and dissolving, adding dopamine into the solution, stirring and dissolving to form a DA-HP compound, adjusting the pH of the system to 9-12 by using a NaOH solution, and stirring at room temperature for 0.2-1h to ensure that DA is pre-polymerized to form a PDA-HP compound;
(2) adding acrylamide into the PDA-HP compound solution obtained in the step (1), then adding 2-acryloyloxy-ethyl-N, N-dimethyl-6-ammonium bromide quaternary ammonium salt, adding an initiator, a cross-linking agent and an initiation aid, uniformly stirring, and carrying out free radical polymerization reaction on the system to generate the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel.
9. A polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel characterized by being obtained by the preparation method according to any one of claims 1 to 8.
10. Use of the polydopamine-heparin/quaternary ammonium salt/polyacrylamide hydrogel according to claim 9 in the field of biomedical materials.
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