CN115160599B - A polydopamine cross-linked polyethylene glycol hydrogel material degradable on demand and its preparation method and application - Google Patents

Abstract

The invention discloses a preparation method of a polydopamine crosslinked polyethylene glycol hydrogel material, which comprises the following steps: s1, enabling an amino-terminated polyethylene glycol solution to react with a cross-linking agent to obtain modified polyethylene glycol; s2, mixing the modified polyethylene glycol obtained in the step S1 with polydopamine nano particles, and stirring to react; s3, oxidizing the mixture obtained in the step S2 with an oxidant to obtain the polydopamine crosslinked polyethylene glycol hydrogel material; wherein the crosslinking agent is a lactone compound comprising the following structure:

n is selected from any integer from 1 to 3; x is sulfur, selenium or tellurium; the polyethylene glycol is double-arm polyethylene glycol, three-arm polyethylene glycol or four-arm polyethylene glycol. The raw material of the polyethylene glycol hydrogel material provided by the invention is commercial polyethylene glycol, the additive is polydopamine with adhesiveness, the functional group of the cross-linking agent has multiple responsiveness, and the controllable degradation of the hydrogel material can be realized by controlling different stimulation conditions, so that the hydrogel material can be used as a medical dressing.

Description

Translated fromChinese

一种按需降解的聚多巴胺交联聚乙二醇水凝胶材料及其制备方法与应用A demand-degradable polydopamine cross-linked polyethylene glycol hydrogel material and its preparationMethod and Application

技术领域technical field

本发明涉及水凝胶材料技术领域，尤其涉及一种按需降解的聚多巴胺交联聚乙二醇水凝胶材料及其制备方法与应用。The invention relates to the technical field of hydrogel materials, in particular to an on-demand degradable polydopamine cross-linked polyethylene glycol hydrogel material and its preparation method and application.

背景技术Background technique

糖尿病创面是糖尿病常见的并发症，严重危害人类健康，目前尚无有效的治疗手段。其特点是伤口环境恶劣、炎症持续时间延长、血管生成减少和上皮再形成异常，导致截肢率和死亡率很高。对于这些慢性伤口，理想的药物治疗方式是在局部长时间保持药物并以按需方式控制药物释放。Diabetic wound is a common complication of diabetes, which seriously endangers human health. At present, there is no effective treatment. It is characterized by a hostile wound environment, prolonged inflammation, reduced angiogenesis, and abnormal re-epithelialization, resulting in high rates of amputation and mortality. For these chronic wounds, the ideal drug treatment modality is to maintain the drug locally for a long time and to control the drug release in an on-demand manner.

一个理想的敷料应具备以下几个条件：(1)能够在几个小时内止血；(2)对组织有一定的粘附力；(3)能够很容易的使用；(4)在创伤清理过程中能够很容易地控制溶解。当前临床有在使用一些烧伤敷料吸收伤口渗出的组织液、防止细菌入侵、保持伤口微环境湿润，但是普遍需要手术或机械清创，对新生成的组织造成额外的损伤。在清创或手术过程中，现有的创口密封体系很少具备以上几点。An ideal dressing should have the following conditions: (1) be able to stop bleeding within a few hours; (2) have a certain degree of adhesion to the tissue; (3) be easy to use; Dissolution can be easily controlled in . Currently, some burn dressings are used clinically to absorb tissue fluid exuded from the wound, prevent bacterial invasion, and keep the wound microenvironment moist, but surgical or mechanical debridement is generally required to cause additional damage to the newly formed tissue. During debridement or surgery, existing wound sealing systems rarely have the above points.

水凝胶是三维、亲水、交联网状聚合物，可以容纳大量水。由于它们的生物相容性、生物降解性能、可控的力学性能，在组织工程、伤口愈合、药物负载等方面引起了人们的普遍关注。理想的水凝胶敷料需满足如下几个方面：(1)在相对温和条件下能够高效制备；(2)结构和力学性能符合预期的应用需要；(3)使用过程中是微创或无创的；(4)良好的生物相容性；(5)容易移除，最好不需要外科或机械清创。合成水凝胶具有化学组成和材料性能可调的特点，如组织粘附力，机械性能，可降解和可溶胀性能都可以在合成中进行设计调整。尽管当前就开发、表征、应用化学交联的水凝胶用于敷料已取得一定成果(有几种水凝胶敷料配方产品已经商品化)，但是目前文献报道具有抗菌、抗氧化、可控释放药物以及按需降解等综合性能的水凝胶敷料仍不是很多。因此发展可降解的水凝胶敷料在基础科学研究上是很有意义的，在临床医学应用上也是富有机会的。Grinstaff教授在可降解水凝胶用于伤口愈合方面的应用做了很多工作，报道了几例基于硫醇-硫酯交换反应的可控降解水凝胶，这类聚合物具有较好的粘附力，可吸收组织液，密封性好等特点，同时还能够可控降解，可以用作微创或无创的敷料同时又是很好的抵抗细菌感染的屏障。但这类材料的合成需要多步反应，保护脱保护等操作，合成难度和成本都很高，应用推广都受到限制。Hydrogels are three-dimensional, hydrophilic, cross-linked polymers that can hold large amounts of water. Due to their biocompatibility, biodegradability, and controllable mechanical properties, they have attracted widespread attention in tissue engineering, wound healing, and drug loading. An ideal hydrogel dressing needs to meet the following aspects: (1) It can be prepared efficiently under relatively mild conditions; (2) The structure and mechanical properties meet the expected application needs; (3) It is minimally invasive or non-invasive during use ; (4) good biocompatibility; (5) easy to remove, preferably without surgical or mechanical debridement. Synthetic hydrogels have the characteristics of tunable chemical composition and material properties, such as tissue adhesion, mechanical properties, degradable and swellable properties can be designed and adjusted during synthesis. Although some progress has been made in the development, characterization, and application of chemically cross-linked hydrogels for dressings (several hydrogel dressing formulations have been commercialized), the current literature reports antibacterial, antioxidant, and controlled release properties. There are still not many hydrogel dressings with comprehensive properties such as drugs and on-demand degradation. Therefore, the development of degradable hydrogel dressings is of great significance in basic scientific research, and it is also full of opportunities in clinical medical applications. Professor Grinstaff has done a lot of work on the application of degradable hydrogels for wound healing, and reported several cases of controlled degradable hydrogels based on thiol-thioester exchange reactions. These polymers have good adhesion It can be used as a minimally invasive or non-invasive dressing and is also a good barrier against bacterial infection. However, the synthesis of such materials requires multi-step reactions, protection and deprotection operations, and the synthesis difficulty and cost are very high, and the application and promotion are limited.

发明内容Contents of the invention

本发明的目的在于提供一种聚多巴胺交联聚乙二醇水凝胶材料，通过在合成过程中加入聚多巴胺纳米粒子，改善了水凝胶的物理性能，提高了水凝胶的粘附力，且该水凝胶可以在氧化或还原的条件下有效剥离，因此可以作为医用敷料使用，有利于创口换药，减少伤者的痛苦。The object of the present invention is to provide a polydopamine cross-linked polyethylene glycol hydrogel material, by adding polydopamine nanoparticles in the synthesis process, the physical properties of the hydrogel are improved, and the adhesion of the hydrogel is improved , and the hydrogel can be effectively peeled off under oxidation or reduction conditions, so it can be used as a medical dressing, which is beneficial to wound dressing change and reduces the pain of the wounded.

为解决上述技术问题，本发明第一方面提供了一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，通过聚乙二醇的氨基开环内酯，生成修饰的聚乙二醇，再使修饰的聚乙二醇与聚多巴胺纳米粒子与硒醇/硫醇/碲醇发生迈克尔加成反应，最后，该聚合物被氧化得到交联的聚乙二醇水凝胶材料。In order to solve the above-mentioned technical problems, the first aspect of the present invention provides a preparation method of polydopamine cross-linked polyethylene glycol hydrogel material, through the amino ring-opening lactone of polyethylene glycol to generate modified polyethylene glycol , and then the modified polyethylene glycol and polydopamine nanoparticles undergo Michael addition reaction with selenol/thiol/tellurol, and finally, the polymer is oxidized to obtain a cross-linked polyethylene glycol hydrogel material.

具体的，所述制备方法包括以下步骤：Specifically, the preparation method includes the following steps:

S1.使端氨基的聚乙二醇溶液与交联剂反应，得到修饰的聚乙二醇；S1. reacting the amino-terminated polyethylene glycol solution with a cross-linking agent to obtain modified polyethylene glycol;

S2.将步骤S1的修饰的聚乙二醇与聚多巴胺纳米颗粒混合，搅拌以发生反应；S2. Mix the modified polyethylene glycol and polydopamine nanoparticles in step S1, and stir to react;

S3.使步骤S2的混合物与氧化剂发生氧化反应，得到所述聚多巴胺交联聚乙二醇水凝胶材料；S3. Oxidizing the mixture in step S2 with an oxidizing agent to obtain the polydopamine cross-linked polyethylene glycol hydrogel material;

其中，所述交联剂为包括具有式(I)所示结构的内酯化合物：Wherein, the cross-linking agent comprises a lactone compound having a structure shown in formula (I):

n选自1～3中的任一整数；X为硫、硒或碲；n is any integer selected from 1 to 3; X is sulfur, selenium or tellurium;

所述聚乙二醇为双臂聚乙二醇、三臂聚乙二醇或四臂聚乙二醇。The polyethylene glycol is two-arm polyethylene glycol, three-arm polyethylene glycol or four-arm polyethylene glycol.

进一步地，步骤S1中，所述聚乙二醇为四臂聚乙二醇，分子量为500-50000；优选的，所述聚乙二醇的分子量为2000-20000；更优选的，所述聚乙二醇的分子量为10000。Further, in step S1, the polyethylene glycol is four-armed polyethylene glycol with a molecular weight of 500-50000; preferably, the molecular weight of the polyethylene glycol is 2000-20000; more preferably, the polyethylene glycol Ethylene glycol has a molecular weight of 10,000.

所述聚乙二醇溶液的浓度为1～80wt％；优选的，所述聚乙二醇溶液的浓度为5～30wt％；更优选的，所述聚乙二醇溶液的浓度为10wt％。The concentration of the polyethylene glycol solution is 1-80 wt %; preferably, the concentration of the polyethylene glycol solution is 5-30 wt %; more preferably, the concentration of the polyethylene glycol solution is 10 wt %.

进一步地，步骤S1中，所述聚乙二醇溶液中的溶剂包括水或磷酸盐缓冲溶液；Further, in step S1, the solvent in the polyethylene glycol solution includes water or phosphate buffer solution;

优选的，所述磷酸盐缓冲溶液的pH值为7.0～8.0，优选为7.4。Preferably, the pH of the phosphate buffer solution is 7.0-8.0, preferably 7.4.

进一步地，步骤S1中，所述反应的温度为0～100℃，反应时间为1～12h。优选的，所述反应的温度为15～30℃，反应时间为6～12h。Further, in step S1, the temperature of the reaction is 0-100° C., and the reaction time is 1-12 h. Preferably, the reaction temperature is 15-30° C., and the reaction time is 6-12 hours.

进一步地，步骤S1中，所述聚乙二醇与交联剂的摩尔比为1:2～4，优选为1:4。Further, in step S1, the molar ratio of the polyethylene glycol to the crosslinking agent is 1:2-4, preferably 1:4.

进一步地，步骤S2中，向所述修饰的聚乙二醇中加入聚多巴胺纳米粒子，搅拌混合5～10min 即可。Further, in step S2, polydopamine nanoparticles are added to the modified polyethylene glycol and stirred for 5-10 minutes.

进一步地，步骤S1和S2中，所述反应是在氮气氛围或氩气氛围下进行发生的。Further, in steps S1 and S2, the reaction is carried out under a nitrogen atmosphere or an argon atmosphere.

进一步地，步骤S2中，所述修饰的聚乙二醇与聚多巴胺纳米粒子的质量比为10000:1～1000；优选的，所述修饰的聚乙二醇与聚多巴胺纳米粒子的质量比为1000:1-100，例如可以为1000:1、1000:10、1000:100。Further, in step S2, the mass ratio of the modified polyethylene glycol to polydopamine nanoparticles is 10000:1-1000; preferably, the mass ratio of the modified polyethylene glycol to polydopamine nanoparticles is 1000:1-100, for example, 1000:1, 1000:10, 1000:100.

进一步地，步骤S3中，所述氧化剂包括空气、氧气、次氯酸钠、双氧水中的任意一种；Further, in step S3, the oxidizing agent includes any one of air, oxygen, sodium hypochlorite, and hydrogen peroxide;

优选的，所述氧化剂选自空气和/或氧气。进一步的，氧化反应中，空气和/或氧气是过量使用的。Preferably, the oxidizing agent is selected from air and/or oxygen. Furthermore, in the oxidation reaction, air and/or oxygen are used in excess.

进一步地，步骤S3中，所述反应温度为0-80℃，反应时间为4～24h。Further, in step S3, the reaction temperature is 0-80° C., and the reaction time is 4-24 hours.

本发明第二方面提供了由所述方法制备得到的聚多巴胺交联聚乙二醇水凝胶材料。The second aspect of the present invention provides the polydopamine cross-linked polyethylene glycol hydrogel material prepared by the method.

本发明第三方面提供了所述的聚多巴胺交联聚乙二醇水凝胶材料作为医用敷料的应用，尤其是作为糖尿病创面敷料的应用。The third aspect of the present invention provides the application of the polydopamine cross-linked polyethylene glycol hydrogel material as a medical dressing, especially as a diabetic wound dressing.

本发明的上述技术方案相比现有技术具有以下优点：The above technical solution of the present invention has the following advantages compared with the prior art:

1.本发明利用端基为氨基的聚乙二醇胺解内酯、开环氧化偶联方法，合成了聚乙二醇水凝胶敷料，该水凝胶敷料具有制备条件简单，合成过程绿色等优点。1. The present invention utilizes polyethylene glycol aminolytic lactone whose terminal group is an amino group, and an epoxy-opening oxidation coupling method to synthesize a polyethylene glycol hydrogel dressing. The hydrogel dressing has simple preparation conditions and a green synthesis process. Etc.

2.本发明在制备的水凝胶中加入聚多巴胺纳米粒子，与硒醇发生迈克尔加成反应，调节水凝胶中二硒醚与单硒醚的含量比，改善了水凝胶的物理性能，提高了水凝胶的粘附力，为水凝胶在糖尿病慢性伤口中的应用提供了保障。2. The present invention adds polydopamine nanoparticles to the prepared hydrogel, and produces Michael addition reaction with selenol, adjusts the content ratio of diselenide and monoselenide in the hydrogel, and improves the physical properties of the hydrogel , which improves the adhesion of the hydrogel and provides a guarantee for the application of the hydrogel in diabetic chronic wounds.

3.本发明制备的的水凝胶材料，在医用敷料中具有很好的应用前景，覆盖在伤口，可以吸收组织液，使用过后，可以在氧化或还原的条件下有效剥离，从而有利于创口换药，减少伤者的痛苦。3. The hydrogel material prepared by the present invention has a good application prospect in medical dressings. It covers the wound and can absorb tissue fluid. After use, it can be effectively peeled off under oxidation or reduction conditions, thereby facilitating wound replacement. Medicines to reduce the suffering of the injured.

附图说明Description of drawings

图1为本发明实施例1中硒内酯修饰后的聚乙二醇核磁图谱；Fig. 1 is the NMR spectrum of polyethylene glycol after selenone lactone modification in the embodiment of thepresent invention 1;

图2是原始的聚乙二醇(PEG)、实施例1-4中的修饰后的聚乙二醇水凝胶敷料P1以及P3 的红外谱图；Fig. 2 is the infrared spectrogram of original polyethylene glycol (PEG), modified polyethylene glycol hydrogel dressing P1 and P3 in embodiments 1-4;

图3a-3d是本发明实施例1-4中所得聚乙二醇水凝胶敷料的凝胶点测定图；Fig. 3a-3d is the gel point determination figure of polyethylene glycol hydrogel dressing obtained in the embodiment of the present invention 1-4;

图4是实施例1和实施例3中得到的聚乙二醇水凝胶敷料的溶胀率随时间的变化图；Fig. 4 is the variation diagram of the swelling rate of the polyethylene glycol hydrogel dressing obtained inembodiment 1 andembodiment 3 with time;

图5是实施例1、2、3、4中的二硒醚水凝胶的失重率随时间的变化图；Fig. 5 is the change graph of the weight loss rate of the diselenide hydrogel over time in Examples 1, 2, 3, and 4;

图6是频率对实施例1、2、3、4中的二硒醚水凝胶P1、P2、P3、P4的G＇和G＂的影响；Fig. 6 is the influence of frequency on G' and G " of diselenide hydrogel P1, P2, P3, P4 inembodiment 1,2,3,4;

图7是应变对实施例1、2、3、4中的二硒醚水凝胶P1、P2、P3、P4的G＇和G＂的影响；Fig. 7 is the effect of strain on G' and G " of diselenide hydrogels P1, P2, P3, P4 inembodiments 1, 2, 3, and 4;

图8是实施例1、2、3、4中得到的二硒醚交联的聚乙二醇水凝胶敷料的粘附力剪切测试结果；Fig. 8 is the adhesion shear test result of the polyethylene glycol hydrogel dressing obtained in the diselenide crosslinking obtained inembodiment 1, 2, 3, 4;

图9是实施例1、3中得到的二硒醚交联的聚乙二醇水凝胶敷料在3wt％双氧水和DTT作用下降解图示；Fig. 9 is the diselenide cross-linked polyethylene glycol hydrogel dressing obtained in Examples 1 and 3, which is degraded under the action of 3wt% hydrogen peroxide and DTT;

图10a-10c是实施例3中得到的二硒醚交联的聚乙二醇水凝胶敷料(固含量10wt％)用3wt％医用双氧水处理后，随时间变化水凝胶逐渐降解的照片。Figures 10a-10c are photos of the gradual degradation of the hydrogel over time after the diselenide cross-linked polyethylene glycol hydrogel dressing (solid content 10wt%) obtained in Example 3 was treated with 3wt% medical hydrogen peroxide.

具体实施方式Detailed ways

下面结合具体实施例对本发明作进一步说明，以使本领域的技术人员可以更好地理解本发明并能予以实施，但所举实施例不作为对本发明的限定。The present invention will be further described below in conjunction with specific examples, so that those skilled in the art can better understand the present invention and implement it, but the given examples are not intended to limit the present invention.

除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。本文所使用的术语“及/或”包括一个或多个相关的所列项目的任意的和所有的组合。Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field of the invention. The terms used herein in the description of the present invention are for the purpose of describing specific embodiments only, and are not intended to limit the present invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

如无特殊说明，本发明实施例所涉及的试剂均为市售产品，均可以通过商业渠道购买获得。Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, which can be purchased through commercial channels.

本发明以下实施例中，所涉及的测试方法如下：In the following examples of the present invention, the involved test methods are as follows:

在HAAKE rheometer(RS 6000)流变仪上测定了已形成水凝胶的流变性能。所有的流变性测量都在37℃下进行，以模拟人体环境。采用25mm平行平板测量测试时转子与样品台的间距为1mm。应变扫描设置：频率为1Hz，应变扫描设置为1～1000％；频率扫描设置：应变为 1.0％，频率扫描设置为1～100Hz。时间扫描测量是在频率为1Hz，应变为1％，扫描时间为300 s。同时，通过流变测试水凝胶的自修复性能，即水凝胶在0.1％和1000％的应变条件下进行交替的120s时间扫描，即0.1％应变下低剪切进行120s后，1000％应变下高剪切进行120s，共进行4个循环，循环完成后再进行一次120s的0.1％应变下低剪切测量，整个过程中频率保持 10Hz不变。The rheological properties of the formed hydrogels were measured on a HAAKE rheometer (RS 6000) rheometer. All rheological measurements were performed at 37°C to mimic the human environment. The distance between the rotor and the sample stage is 1mm when a 25mm parallel flat plate is used to measure and test. Strain sweep setting: frequency is 1Hz, strain sweep setting is 1~1000%; frequency sweep setting: strain is 1.0%, frequency sweep setting is 1~100Hz. The time-sweep measurement is performed at a frequency of 1 Hz, a strain of 1%, and a sweep time of 300 s. At the same time, the self-healing performance of the hydrogel was tested by rheology, that is, the hydrogel was subjected to alternating 120s time sweeps under the strain conditions of 0.1% and 1000%, that is, after 120s of low shear at 0.1% strain, the 1000% strain Under high shear for 120s, a total of 4 cycles were performed, and then a 120s low-shear measurement under 0.1% strain was performed after the cycle was completed, and the frequency remained constant at 10 Hz throughout the process.

根据ASTM标准F2255-05方法，使用万能试验机(Tinius Olsen型号H10KS)在37℃下通过拉伸搭接剪切试验研究聚乙二醇水凝胶对皮肤的粘附强度。将新鲜猪皮切成2×2cm大小和约1mm厚的矩形切片，并始终保持湿润。总共使用0.2g水凝胶均匀涂覆第一条带的1×1 cm区域。随后，将第二个条带与第一个条带(对应于水凝胶涂层表面的重叠区域)接触，并将所得搭接剪切样品置于室温下的潮湿室中1小时，然后再进行测试。然后以10mm·min^–1的十字头速度对样品进行测试(拉伸机配备5000N称重传感器)并确定最大粘合强度。The adhesion strength of polyethylene glycol hydrogel to skin was investigated by tensile lap shear test using a universal testing machine (Tinius Olsen model H10KS) at 37 °C according to ASTM standard F2255-05 method. Cut the fresh pigskin into rectangular slices with a size of 2×2cm and a thickness of about 1mm, and keep them moist all the time. A total of 0.2 g of hydrogel was used to evenly coat a 1 × 1 cm area of the first strip. Subsequently, the second strip was brought into contact with the first strip (corresponding to the overlapping area of the hydrogel-coated surface), and the resulting lap-shear sample was placed in a humid chamber at room temperature for 1 h, and then carry out testing. The samples were then tested at a crosshead speed of 10 mm min⁻¹ (tensile machine equipped with a 5000 N load cell) and the maximum bond strength determined.

实施例1Example 1

在氩气保护下，将硒内酯(60mg)滴加到聚乙二醇水溶液(10g，10wt％)，在25℃条件下反应10h后得到硒醇修饰的聚乙二醇，聚合物不需分离纯化直接投入下一步使用，聚乙二醇的修饰率经过核磁测定。Under argon protection, selenolactone (60mg) was added dropwise to polyethylene glycol aqueous solution (10g, 10wt%), and after reacting for 10h at 25°C, selenol-modified polyethylene glycol was obtained, and the polymer did not need Separation and purification are directly used in the next step, and the modification rate of polyethylene glycol is determined by NMR.

聚乙二醇水凝胶敷料(P1)在25℃条件下直接敞口放置，凝胶的形成过程通过流变测试或倒瓶实验监测。The polyethylene glycol hydrogel dressing (P1) was directly placed in the open at 25°C, and the gel formation process was monitored by rheological tests or bottle inversion experiments.

实施例2Example 2

本实施例中，按照质量比为[聚乙二醇]₀:[聚多巴胺]₀＝1000:1，将实施例1中修饰的聚乙二醇与聚多巴胺纳米粒子混合，使硒醇与聚多巴胺发生反应，其他反应步骤和反应条件与实施例1 相同，得到聚乙二醇水凝胶敷料(P2)。In the present embodiment, according to the mass ratio is [polyethylene glycol]_α :[polydopamine]_α =1000:1, the polyethylene glycol modified in Example 1 is mixed with polydopamine nanoparticles, so that selenol and polydopamine Dopamine reacted, and other reaction steps and reaction conditions were the same as in Example 1 to obtain a polyethylene glycol hydrogel dressing (P2).

实施例3Example 3

本实施例中，按照质量比为[聚乙二醇]₀:[聚多巴胺]₀＝100:1，将实施例1中修饰的聚乙二醇与聚多巴胺纳米粒子混合，使硒醇与聚多巴胺发生反应，其他反应步骤和反应条件与实施例1 相同，得到聚乙二醇水凝胶敷料(P3)。In the present embodiment, according to the mass ratio is [polyethylene glycol]_α :[polydopamine]_α =100:1, the polyethylene glycol modified in Example 1 is mixed with polydopamine nanoparticles, so that selenol and polydopamine Dopamine reacted, and other reaction steps and reaction conditions were the same as in Example 1 to obtain a polyethylene glycol hydrogel dressing (P3).

实施例4Example 4

本实施例中，按照质量比为[聚乙二醇]₀:[聚多巴胺]₀＝10:1，将实施例1中修饰的聚乙二醇与聚多巴胺纳米粒子混合，使硒醇与聚多巴胺发生反应，其他反应步骤和反应条件与实施例1 相同，得到聚乙二醇水凝胶敷料(P4)。In the present embodiment, according to the mass ratio is [polyethylene glycol]_α :[polydopamine]_α =10:1, the polyethylene glycol modified inembodiment 1 is mixed with polydopamine nanoparticles, so that selenol and polydopamine Dopamine reacted, and other reaction steps and reaction conditions were the same as in Example 1 to obtain a polyethylene glycol hydrogel dressing (P4).

性能测试Performance Testing

图1是实施例1-4中的修饰后的聚乙二醇水凝胶敷料P1以及原始的聚乙二醇(PEG)，聚乙二醇经硒内酯修饰后所得聚合物的¹H NMR谱图。通过核磁氢谱可以观测到硒内酯成功被胺解，聚合物链上水解片段的质子化学位移在2.8ppm左右，通过核磁检测，可以证实成功制得硒内酯修饰的聚乙二醇。Fig. 1 is the polyethylene glycol hydrogel dressing P1 after modification in embodiment 1-4 and original polyethylene glycol (PEG),^{the 1} H NMR of polymer obtained after polyethylene glycol is modified by selenolactone spectrogram. It can be observed by proton nuclear magnetic spectrum that selenone is successfully aminated, and the proton chemical shift of the hydrolyzed fragment on the polymer chain is about 2.8ppm. Through nuclear magnetic detection, it can be confirmed that selenone-modified polyethylene glycol has been successfully prepared.

图2是原始的聚乙二醇(PEG)、实施例1-4中的修饰后的聚乙二醇水凝胶敷料P1以及P3 的红外谱图。通过红外检测，证实了聚多巴胺与硒醇的反应。Fig. 2 is the infrared spectra of the original polyethylene glycol (PEG), the modified polyethylene glycol hydrogel dressings P1 and P3 in Examples 1-4. The reaction between polydopamine and selenol was confirmed by infrared detection.

1.四种聚多巴胺含量不同的聚合物敷料凝胶点的测定1. Determination of the gel point of four polymer dressings with different polydopamine contents

时间扫描是测试材料力学性能随时间的变化。聚合物水溶液的交联动力学使用直径25mm 的平板夹具，测试频率为1Hz，应变为1％，经时间扫描测得。整个测试在空气条件下进行以保证硒醇充分氧化偶联成硒醚，并且制样温度控制在20℃以尽可能减少因溶剂挥发导致的系统误差。同样方法测试不同聚多巴胺含量的聚合物溶液的凝胶点。Time sweep is to test the change of mechanical properties of materials with time. The cross-linking kinetics of the polymer aqueous solution was measured by time sweep using a flat fixture with a diameter of 25 mm, the test frequency was 1 Hz, and the strain was 1%. The entire test was carried out under air conditions to ensure that selenol was fully oxidatively coupled to selenoether, and the sample preparation temperature was controlled at 20°C to minimize systematic errors caused by solvent volatilization. The same method was used to test the gel points of polymer solutions with different polydopamine contents.

图3a、图3b、图3c、图3d分别是实施例1、实施例2、实施例3和实施例4中，硒醇修饰的聚合物水凝胶敷料凝胶点的测定图，其中，图3a代表的是未加聚多巴胺的聚乙二醇水凝胶P1，图3b代表的是加入聚多巴胺质量百分含量0.1％的聚乙二醇水凝胶P2，图3c代表的是加入聚多巴胺质量百分含量1％的聚乙二醇水凝胶P3，图3d代表的是加入聚多巴胺质量百分含量10％的聚乙二醇水凝胶P4。聚合物水凝胶敷料的制备是通过氧化硒醇偶联实现的，本发明使用了空气直接氧化，通过时间扫描跟踪凝胶的形成过程。为保持实验结果的统一性和可对比性，统一使用聚合物含量10wt％的水溶液进行成胶测试，观察其力学性能随时间的变化，储存模量G＇和损耗模量G＂的交点即为凝胶化点。Fig. 3a, Fig. 3b, Fig. 3c, Fig. 3d are respectively inembodiment 1,embodiment 2,embodiment 3 andembodiment 4, the mensuration figure of the polymer hydrogel dressing gel point modified by selenol, wherein, Fig. 3a represents the polyethylene glycol hydrogel P1 without polydopamine added, Figure 3b represents the polyethylene glycol hydrogel P2 with 0.1% polydopamine added by mass, and Figure 3c represents the polydopamine added The polyethylene glycol hydrogel P3 with a mass percentage content of 1%, and Figure 3d represents the polyethylene glycol hydrogel P4 with a mass percentage content of 10% polydopamine. The preparation of the polymer hydrogel dressing is realized through the coupling of oxidized selenol, and the present invention uses air direct oxidation, and tracks the formation process of the gel through time scanning. In order to maintain the uniformity and comparability of the experimental results, an aqueous solution with a polymer content of 10wt% was uniformly used for the gel test, and the change of its mechanical properties over time was observed. The intersection point of the storage modulus G' and the loss modulus G" is gelation point.

从图中可以看出，当加入聚多巴胺质量最多，为被修饰的聚乙二醇的10％时，凝胶化速度也最快，经过3.7h就能观测到材料的储能模量超过损耗模量(图3d)。当加入聚多巴胺质量为被修饰的聚乙二醇的1％时，凝胶化速度次之，需要4.5h(图3c)。而加入聚多巴胺质量为被修饰的聚乙二醇的0.1％时，凝胶化速度反而比不加聚多巴胺时的4.8h(图3a)更长，为6.3h (图3b)。这一实验结果表明，加入适量的聚多巴胺，可以有效缩短水凝胶敷料的成胶时间。It can be seen from the figure that when the mass of polydopamine is the most added, which is 10% of the modified polyethylene glycol, the gelation speed is also the fastest, and it can be observed that the storage modulus of the material exceeds the loss after 3.7 hours modulus (Fig. 3d). When the mass of polydopamine was added to be 1% of the modified polyethylene glycol, the gelation speed was next, and it took 4.5 hours (Fig. 3c). However, when the mass of polydopamine was added to be 0.1% of the modified polyethylene glycol, the gelation rate was 6.3h (Fig. 3b), which was longer than 4.8h (Fig. 3a) without polydopamine. This experimental result shows that adding an appropriate amount of polydopamine can effectively shorten the gelation time of the hydrogel dressing.

2.聚合物水凝胶敷料的溶胀性能测试2. Swellability test of polymer hydrogel dressing

聚多巴胺含量不同的水凝胶P1、P3制成5mm*5mm*2mm的薄片，冷冻干燥至重量不再发生变化。。将样品浸入到10mL磷酸缓冲盐(phosphate buffer saline，PBS)溶液中(10mmol/L， pH＝7.4)，室温下溶胀，定时取出样品称量计算溶胀率，直至达到溶胀平衡。溶胀率通过以下公式计算：Hydrogels P1 and P3 with different polydopamine contents were made into thin slices of 5mm*5mm*2mm, and freeze-dried until the weight did not change. . The sample was immersed in 10 mL of phosphate buffer saline (PBS) solution (10 mmol/L, pH=7.4), and swelled at room temperature, and the sample was taken out periodically to weigh and calculate the swelling rate until the swelling equilibrium was reached. The swelling rate is calculated by the following formula:

W_s表示溶胀一定时间后水凝胶的质量，W₀表示水凝胶初始质量。所有样品均测试三次，取平均值。W_s represents the mass of the hydrogel after swelling for a certain period of time, and W₀ represents the initial mass of the hydrogel. All samples were tested three times and the average value was taken.

图4是实施例1和实施例3中得到的聚乙二醇水凝胶敷料的溶胀率随时间的变化图。实验发现：当水凝胶敷料中未加入聚多巴胺时(P1)，水凝胶敷料在溶胀过程中非常不稳定，随着时间的推移崩解成极小碎片而使水凝胶的溶胀率不升反降。而当加入聚多巴胺以后水凝胶就能较为稳定的在PBS中溶胀，溶胀率可达1700％。Fig. 4 is the variation diagram of the swelling rate of the polyethylene glycol hydrogel dressing obtained in Example 1 and Example 3 with time. The experiment found that: when polydopamine was not added to the hydrogel dressing (P1), the hydrogel dressing was very unstable during the swelling process, and disintegrated into very small fragments over time so that the swelling rate of the hydrogel was not high. Up and down. However, when polydopamine is added, the hydrogel can swell in PBS more stably, and the swelling rate can reach 1700%.

3.水凝胶敷料的体外降解性能3. In vitro degradation performance of hydrogel dressings

以PBS缓冲溶液(0.1M，pH 7.4)作为体外降解介质，将水凝胶干燥后的材料置于10ml 离心管中并做好标记，放置于37℃恒温恒湿箱2周后，观察其降解规律。具体方法为，取一定量的水凝胶，利用冷冻干燥机将其水分除去，称重记为M_d1，将冻干后的水凝胶放入含有一定量的PBS的10ml离心管中并做好标记，放置于37℃恒温恒湿箱中，每隔一定的时间取出离心管，取出水凝胶利用冷冻干燥机除去凝胶多余水分，称重记为M_d2。失重率率通过以下公式计算：Using PBS buffer solution (0.1M, pH 7.4) as the in vitro degradation medium, put the dried material of the hydrogel into a 10ml centrifuge tube and mark it, place it in a constant temperature and humidity box at 37°C for 2 weeks, and observe its degradation law. The specific method is as follows: take a certain amount of hydrogel, use a freeze dryer to remove its moisture, weigh it and record it as M_d1 , put the freeze-dried hydrogel into a 10ml centrifuge tube containing a certain amount of PBS and make Mark well, place in a constant temperature and humidity box at 37°C, take out the centrifuge tube at regular intervals, take out the hydrogel and use a freeze dryer to remove excess water from the gel, weigh it and record it as M_d2 . The rate of weight loss is calculated by the following formula:

降解率＝M_d2/M_d1×100％Degradation rate = M_d2 /M_d1 × 100%

图5是实施例1、2、3、4中的二硒醚水凝胶的失重率随时间的变化图。实验发现：相同时间内，聚合物水凝胶敷料的降解速度随着加入聚多巴胺量的增多而减小，即降解速度P1＞P2 ＞P3＞P4。证明聚多巴胺的加入能有效稳定二硒醚水凝胶过于活泼的特性。Fig. 5 is a graph showing the change in weight loss rate of diselenide hydrogels over time in Examples 1, 2, 3, and 4. The experiment found that: within the same period of time, the degradation rate of the polymer hydrogel dressing decreases with the increase of the amount of polydopamine added, that is, the degradation rate P1>P2>P3>P4. It is proved that the addition of polydopamine can effectively stabilize the overactive properties of diselenide hydrogel.

4.聚合物水凝胶敷料的力学性能测试4. Mechanical property test of polymer hydrogel dressing

本实验通过流变测试水凝胶的力学性能(储存模量和损耗模量)。In this experiment, the mechanical properties (storage modulus and loss modulus) of the hydrogel were tested by rheology.

频率扫描是在恒定应变下测试材料力学性能随频率的响应。设置应变为1％，频率从1至10 Hz，使用直径25mm平板夹具，测试温度为37℃。样品用pH值为7.4的PBS缓冲溶液控制用量溶胀至10％固含量。每个样品至少三次测试结果取平均值。Frequency sweep is to test the response of material mechanical properties with frequency under constant strain. Set the strain to 1%, frequency from 1 to 10 Hz, use a flat plate fixture with a diameter of 25 mm, and test temperature at 37 °C. The sample was swelled with a controlled amount of PBS buffer solution with a pH value of 7.4 to 10% solid content. At least three test results for each sample were averaged.

应变扫描测试是在震荡频率恒定条件下测试材料力学性能随应变的变化。设置震荡频率为1 Hz，应变范围0.1％-1000％，使用直径25mm平板夹具，测试温度为37℃。水凝胶样品用pH 值为7.4的PBS缓冲溶液控制用量溶胀至10％固含量。每个样品至少三次测试结果取平均值。The strain sweep test is to test the change of mechanical properties of materials with strain under the condition of constant oscillation frequency. Set the oscillation frequency to 1 Hz, the strain range from 0.1% to 1000%, use a flat fixture with a diameter of 25mm, and test the temperature at 37°C. The hydrogel sample was swelled with a controlled amount of PBS buffer solution with a pH value of 7.4 to 10% solid content. At least three test results for each sample were averaged.

图6是频率对实施例1、2、3、4中的二硒醚水凝胶P1、P2、P3、P4的G＇和G＂的影响。图7是应变对实施例1、2、3、4中的二硒醚水凝胶P1、P2、P3、P4的G＇和G＂的影响。本发明进行了应变扫描测试，这样可以确定材料的线性粘弹性，同时确定材料的弹性是否因加入聚多巴胺不同而有所变化。这些性质可以通过储存模量(G＇)来表示，材料的应变扫描测试结果见图7，结果显示材料的储存模量(G＇)始终占主导地位，这个结论在频率扫描测试中同样得到支持(图6)，这说明固含量为10％时，储存模量(G＇)比损耗模量(G＂)高一至两个数量级，水凝胶弹性比粘性要高。随着应变的增大，P2储存模量(G＇)比损耗模量(G＂)仍然要高，但是两者间的差距已经明显缩小。另外，P3的弹性是四种水凝胶中最好的。这说明随着加入聚多巴胺的增加，水凝胶的模量呈现先增大后减小的趋势。Fig. 6 is the influence of frequency on G' and G " of the diselenide hydrogel P1, P2, P3, P4 inembodiment 1,2,3,4. Fig. 7 is the effect of strain onembodiment 1,2,3 , 4 in the diselenide hydrogel P1, P2, P3, P4 G' and G "influence. The invention carries out a strain scanning test, so that the linear viscoelasticity of the material can be determined, and at the same time, it can be determined whether the elasticity of the material changes due to the addition of polydopamine. These properties can be represented by the storage modulus (G'). The strain sweep test results of the material are shown in Figure 7. The results show that the storage modulus (G') of the material is always dominant. This conclusion is also supported by the frequency sweep test. (Figure 6), which shows that when the solid content is 10%, the storage modulus (G') is one to two orders of magnitude higher than the loss modulus (G"), and the hydrogel elasticity is higher than the viscosity. With the increase of strain , the P2 storage modulus (G') is still higher than the loss modulus (G"), but the gap between the two has narrowed significantly. In addition, the elasticity of P3 was the best among the four hydrogels. This shows that with the increase of polydopamine added, the modulus of the hydrogel first increases and then decreases.

5.聚合物水凝胶敷料的搭接剪切强度测试5. Lap shear strength test of polymer hydrogel dressing

搭接剪切强度测定参照美国材料与试验协会(US-ASTM)发布的ASTM F2255-05标准测试方法，该法是通过拉伸载荷测定搭接剪切状态下组织粘合剂强度特性的标准试验方法，专门针对外科用胶粘剂或密封剂的组织粘合强度测试。测试过程中，使用25х25mm见方的猪皮为载体做模型测试，将0.9g充分干燥的凝胶浸润到2.1g PBS缓冲溶液(0.1M，pH7.4)中，充分浸润平衡，制备成凝胶含量30wt％水凝胶体系，在两块新鲜猪皮上均匀涂抹1-2mm的敷料，两块猪皮搭接宽度1.0±0.1cm，潮湿环境下静置稳定1h，测试前样品先在温度控制箱中37℃稳定15min，测试过程中保持移动速度为10mm·min^-1，直至搭接样品完全分离。每个样品测试五次，取平均值。The lap shear strength is measured with reference to the ASTM F2255-05 standard test method issued by the American Society for Testing and Materials (US-ASTM), which is a standard test for determining the strength characteristics of tissue adhesives under lap shear through tensile loads Method specifically for tissue bond strength testing of surgical adhesives or sealants. During the test, a 25х25mm square pigskin was used as a carrier for model testing, and 0.9g of fully dried gel was soaked into 2.1g of PBS buffer solution (0.1M, pH 7.4) to fully infiltrate and balance, and the gel content was prepared 30wt% hydrogel system, apply 1-2mm dressing evenly on two pieces of fresh pigskin, the overlap width of the two pieces of pigskin is 1.0±0.1cm, stand in a humid environment for 1 hour, and the sample is placed in a temperature control box before testing Stable at 37°C for 15 minutes, and keep the moving speed at 10mm·min^-1 during the test until the lapped samples are completely separated. Each sample was tested five times and the average value was taken.

图8是实施例1、2、3、4中得到的二硒醚交联的聚乙二醇水凝胶敷料的粘附力剪切测试结果。测试结果表明，加入聚多巴胺能有效改善水凝胶敷料的粘附力大小，并且获得的水凝胶敷料对多种基材都具备较好的粘附力。尤其是P4，在玻璃上的粘附强度能达到80KPa。因此，所得水凝胶具有适合的力学强度，在使用中可以保证操作简单，不易从组织剥离脱落。Fig. 8 is the adhesion shear test result of the diselenide cross-linked polyethylene glycol hydrogel dressing obtained in Examples 1, 2, 3 and 4. The test results show that the addition of polydopamine can effectively improve the adhesion of the hydrogel dressing, and the obtained hydrogel dressing has good adhesion to various substrates. Especially for P4, the adhesion strength on glass can reach 80KPa. Therefore, the obtained hydrogel has suitable mechanical strength, which can ensure simple operation and is not easy to be peeled off from the tissue during use.

6.聚乙二醇水凝胶敷料可控按需降解性能测试6. Controllable on-demand degradation performance test of polyethylene glycol hydrogel dressing

首先用0.1％的PBS溶液(pH值为7.4)将聚合物干凝胶充分溶胀至10wt％固含量水凝胶体系，制成25*25mm见方、5mm厚的聚合物膜，然后将样品覆盖在新鲜的猪皮上，用蘸有3wt％医用双氧水的纱布轻轻擦拭猪皮上的水凝胶。为了有效对比双氧水处理前后的变化，留一半样品不作任何处理。First, 0.1% PBS solution (pH value 7.4) was used to fully swell the polymer xerogel to a 10wt% solid content hydrogel system to make a 25*25mm square, 5mm thick polymer film, and then cover the sample on On fresh pigskin, gently wipe the hydrogel on the pigskin with gauze dipped in 3wt% medical hydrogen peroxide. In order to effectively compare the changes before and after hydrogen peroxide treatment, half of the samples were left without any treatment.

另外发明人利用倒瓶实验验证了水凝胶在双氧水作用下的降解性能。取0.1％的PBS溶液 (pH＝7.4)充分溶胀的水凝胶2g(10wt％)置于透明玻璃瓶中，加入0.5mL 3wt％医用双氧水，直接观察水凝胶被双氧水氧化并记录反应所需时间。In addition, the inventor verified the degradation performance of the hydrogel under the action of hydrogen peroxide by using an inverted bottle experiment. Take 2g (10wt%) of hydrogel fully swollen by 0.1% PBS solution (pH = 7.4) and place it in a transparent glass bottle, add 0.5mL 3wt% medical hydrogen peroxide, directly observe the hydrogel being oxidized by hydrogen peroxide and record the reaction required time.

水凝胶的还原降解也是用倒瓶实验观测得到，将1g(10wt％)水凝胶置于透明玻璃瓶中，加入0.2g二硫苏糖醇(DTT)作还原剂，稍加震荡直至溶解完全，记录反应所需时间。The reductive degradation of the hydrogel was also observed by an inverted bottle experiment. 1 g (10 wt%) of the hydrogel was placed in a transparent glass bottle, and 0.2 g of dithiothreitol (DTT) was added as a reducing agent, and it was slightly shaken until it was dissolved. Completely, record the time required for the reaction.

图9是实施例1、3中得到的二硒醚交联的聚乙二醇水凝胶敷料在3wt％双氧水和二硫苏糖醇(DTT)作用下的降解图示，使用2g的水凝胶，加入0.5mL双氧水(3wt％)进行氧化，10 min后凝胶完全溶解。使用DTT作为还原试剂，控制水凝胶的降解，实验发现，15min水凝胶同样能够被有效降解。Fig. 9 is the degradation diagram of the diselenide cross-linked polyethylene glycol hydrogel dressing obtained in Examples 1 and 3 under the action of 3wt% hydrogen peroxide and dithiothreitol (DTT), using 2g of hydrogel Gel was oxidized by adding 0.5mL hydrogen peroxide (3wt%), and the gel was completely dissolved after 10 min. Using DTT as a reducing agent to control the degradation of the hydrogel, it was found that the 15min hydrogel can also be effectively degraded.

图10a-10c是实施例3中得到的二硒醚交联的聚乙二醇水凝胶敷料(固含量10wt％)用3wt％医用双氧水处理后，随时间变化水凝胶逐渐降解的照片，其中图10a-10c的时间分别为：(a)0min， (b)10min，(c)20min。在新鲜猪皮上敷上水凝胶，用浸泡了双氧水的纱布进行擦拭，水凝胶缓慢液化，20min后，水凝胶完全去除干净，而没有经双氧水擦拭的水凝胶仍然保持完好的形状。 3wt％的双氧水是医院诊所常用的伤口消毒剂，在控制水凝胶降解时，还能够对伤口进行消毒。因此二硒醚水凝胶控制降解不需要额外加入处理试剂，使用的医用双氧水来源广泛，价格低廉，处理伤口也不会留下其他有毒有害物质，具有很好的综合效应。此外对一些比较敏感的组织，还可以通过加入还原剂的方法实现水凝胶的降解。Fig. 10a-10c is after the diselenide cross-linked polyethylene glycol hydrogel dressing (10wt% solid content) that obtains inembodiment 3 is treated with 3wt% medical hydrogen peroxide, the photograph that hydrogel degrades gradually over time, The times in Figures 10a-10c are: (a) 0min, (b) 10min, (c) 20min. Apply hydrogel on fresh pigskin, wipe it with gauze soaked in hydrogen peroxide, the hydrogel slowly liquefies, and after 20 minutes, the hydrogel is completely removed, while the hydrogel that has not been wiped with hydrogen peroxide still maintains its intact shape. 3wt% hydrogen peroxide is a commonly used wound disinfectant in hospitals and clinics, and it can also disinfect the wound while controlling the degradation of the hydrogel. Therefore, the diselenide hydrogel does not need to add additional treatment reagents to control the degradation. The medical hydrogen peroxide used has a wide range of sources and is cheap. It will not leave other toxic and harmful substances in the treatment of wounds, and has a good comprehensive effect. In addition, for some sensitive tissues, the degradation of the hydrogel can also be achieved by adding a reducing agent.

显然，上述实施例仅仅是为清楚地说明所作的举例，并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。Apparently, the above-mentioned embodiments are only examples for clear description, and are not intended to limit the implementation. For those of ordinary skill in the art, on the basis of the above description, other changes or changes in various forms can also be made. It is not necessary and impossible to exhaustively list all the implementation manners here. And the obvious changes or changes derived therefrom are still within the scope of protection of the present invention.

Claims (10)

Translated fromChinese

1.一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，包括以下步骤：1. a preparation method of polydopamine cross-linked polyethylene glycol hydrogel material, is characterized in that, comprises the following steps:S1.使端氨基的聚乙二醇溶液与交联剂反应，得到修饰的聚乙二醇；S1. reacting the amino-terminated polyethylene glycol solution with a cross-linking agent to obtain modified polyethylene glycol;S2.将步骤S1的修饰的聚乙二醇与聚多巴胺纳米颗粒混合，搅拌以发生反应；S2. Mix the modified polyethylene glycol and polydopamine nanoparticles in step S1, and stir to react;S3.使步骤S2的混合物与氧化剂发生氧化反应，得到所述聚多巴胺交联聚乙二醇水凝胶材料；其中，所述交联剂为包括具有式(I)所示结构的内酯化合物：S3. Oxidize the mixture in step S2 with an oxidizing agent to obtain the polydopamine cross-linked polyethylene glycol hydrogel material; wherein, the cross-linking agent comprises a lactone compound having a structure shown in formula (I) :

（I）

(I)n选自1～3中的任一整数；X为硫、硒、碲；所述聚乙二醇为双臂聚乙二醇、三臂聚乙二醇或四臂聚乙二醇。n is any integer selected from 1 to 3; X is sulfur, selenium, tellurium; the polyethylene glycol is double-arm polyethylene glycol, three-arm polyethylene glycol or four-arm polyethylene glycol.2.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S1中，所述聚乙二醇为四臂聚乙二醇，分子量为500-50000；所述聚乙二醇溶液的浓度为1～80wt％。2. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S1, described polyethylene glycol is four-armed polyethylene glycol, molecular weight 500-50000; the concentration of the polyethylene glycol solution is 1-80 wt%.3.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S1中，所述聚乙二醇溶液中的溶剂包括水和/或磷酸盐缓冲溶液。3. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S1, the solvent in described polyethylene glycol solution comprises water and/or Phosphate buffer solution.4.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S1中，所述聚乙二醇与交联剂的摩尔比为1:2～4。4. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S1, the mol ratio of described polyethylene glycol and cross-linking agent is 1 : 2~4.5.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S1和S2中，所述反应是在氮气氛围或氩气氛围下进行发生的。5. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S1 and S2, described reaction is to carry out under nitrogen atmosphere or argon atmosphere occurring.6.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S2中，所述修饰的聚乙二醇与聚多巴胺纳米粒子的质量比为10000:1～1000。6. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S2, the quality of the polyethylene glycol of described modification and polydopamine nanoparticle The ratio is 10000:1～1000.7.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S3中，所述氧化剂包括空气、氧气、次氯酸钠、双氧水中的任意一种。7. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S3, described oxidizing agent comprises any one of air, oxygen, sodium hypochlorite, hydrogen peroxide kind.8.根据权利要求1所述的一种聚多巴胺交联聚乙二醇水凝胶材料的制备方法，其特征在于，步骤S1中，所述反应的温度为0～100°C，反应时间为1～12h；8. the preparation method of a kind of polydopamine cross-linked polyethylene glycol hydrogel material according to claim 1, is characterized in that, in step S1, the temperature of described reaction is 0～100 ℃, and the reaction time is 1～12h;步骤S3中，所述反应温度为0～80°C，反应时间为4～24h。In step S3, the reaction temperature is 0-80°C, and the reaction time is 4-24h.9.根据权利要求1～8任一项所述方法制备得到的聚多巴胺交联聚乙二醇水凝胶材料。9. The polydopamine cross-linked polyethylene glycol hydrogel material prepared according to the method according to any one of claims 1-8.10.权利要求9所述的聚多巴胺交联聚乙二醇水凝胶材料作为医用敷料的应用。10. the application of the polydopamine cross-linked polyethylene glycol hydrogel material as claimed in claim 9 as a medical dressing.

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