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CN101161295A - Method for modifying medical metallic grafting body surface collagen by galvano-chemistry method - Google Patents

Method for modifying medical metallic grafting body surface collagen by galvano-chemistry method Download PDF

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CN101161295A
CN101161295A CNA2007101565517A CN200710156551A CN101161295A CN 101161295 A CN101161295 A CN 101161295A CN A2007101565517 A CNA2007101565517 A CN A2007101565517A CN 200710156551 A CN200710156551 A CN 200710156551A CN 101161295 A CN101161295 A CN 101161295A
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collagen
medical metal
solution
metal implant
medical
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翁文剑
苗顺东
程逵
宋晨路
杜丕一
沈鸽
赵高凌
张溪文
徐刚
汪建勋
韩高荣
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Zhejiang University ZJU
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Abstract

本发明公开了采用电化学法对医用金属移植体表面胶原改性的方法。该方法以医用金属移植体为工作电极,铂为参考电极,在溶解有胶原分子的电解质溶液中,通过电极反应使胶原分子自组装成为胶原纤维,并附着在医用金属移植体表面形成胶原纤维层。胶原作为细胞外基质的主要成分,能有效提高医用金属表面的生物相容性和生物活性。采用本发明方法获得的胶原改性医用金属移植体解决了商业医用金属生物移植体表面生物活性有限,不利于组织修复,所需治愈时间长等缺点。本发明制备工艺简单、高效、易于产业化。The invention discloses a method for modifying collagen on the surface of a medical metal implant by using an electrochemical method. In this method, the medical metal implant is used as the working electrode, and platinum is used as the reference electrode. In the electrolyte solution in which collagen molecules are dissolved, the collagen molecules are self-assembled into collagen fibers through electrode reaction, and are attached to the surface of the medical metal implant to form a collagen fiber layer. . Collagen, as the main component of extracellular matrix, can effectively improve the biocompatibility and bioactivity of medical metal surfaces. The collagen-modified medical metal implant obtained by the method of the invention solves the disadvantages of limited biological activity on the surface of the commercial medical metal biological implant, which is not conducive to tissue repair, and requires a long healing time. The preparation process of the invention is simple, efficient and easy for industrialization.

Description

电化学法对医用金属移植体表面胶原改性的方法 Electrochemical Method for Collagen Modification on the Surface of Medical Metal Implants

技术领域technical field

本发明涉及一种用作硬组织修复或替代的一种电化学法对医用金属移植体表面胶原改性的方法。The invention relates to a method for modifying collagen on the surface of a medical metal implant by an electrochemical method for hard tissue repair or replacement.

背景技术Background technique

医用金属材料,如钛及其合金、钴铬钼合金和医用不锈钢等由于具有良好的生物相容性和优良的力学性能,已被广泛的应用于临床治疗骨科、牙科等应组织创伤或疾病。如中国专利CN1064610采用等离子喷涂工艺在齿科金属表面制备羟基磷灰石涂层,中国专利CN1316274采用电解沉积法制备羟基磷灰石涂层等。但是单纯的羟基磷灰石涂层生物活性有限,这使得植入体在体内与骨组织结合缓慢,治愈期长,效果不佳。利用电化学反应可在金属基体周围的电解质溶液产生pH梯度,为胶原分子自组装提供反应动力和微环境,获得胶原改性的表面,是增强医用移植体材料生物活性,加快早期治愈速度的理想方法。Medical metal materials, such as titanium and its alloys, cobalt-chromium-molybdenum alloys, and medical stainless steel, have been widely used in clinical treatment of tissue trauma or diseases in orthopedics and dentistry due to their good biocompatibility and excellent mechanical properties. For example, the Chinese patent CN1064610 adopts a plasma spraying process to prepare a hydroxyapatite coating on the dental metal surface, and the Chinese patent CN1316274 adopts an electrolytic deposition method to prepare a hydroxyapatite coating, etc. However, the pure hydroxyapatite coating has limited biological activity, which makes the implant slowly combine with the bone tissue in vivo, resulting in a long healing period and poor effect. Electrochemical reactions can be used to generate a pH gradient in the electrolyte solution around the metal matrix, providing reaction power and microenvironment for the self-assembly of collagen molecules, and obtaining a collagen-modified surface, which is ideal for enhancing the bioactivity of medical implant materials and speeding up early healing. method.

发明内容Contents of the invention

本发明的目的在于提供一种采用电化学方法对医用金属移植体表面胶原改性的方法,以提高医用金属表面生物活性,优化其临床应用效能,缩短治愈时间。The purpose of the present invention is to provide a method for modifying collagen on the surface of medical metal implants by electrochemical methods, so as to improve the bioactivity of the medical metal surface, optimize its clinical application efficiency, and shorten the healing time.

用电化学法对医用金属移植体表面胶原改性的方法,包括以下步骤:A method for modifying collagen on the surface of a medical metal implant by an electrochemical method, comprising the following steps:

1)将胶原加入pH值为1~4的酸性溶液中,搅拌溶解,配制胶原浓度为0.05g/L~5.0g/L的A溶液并置于4℃下;1) Add collagen into an acidic solution with a pH value of 1-4, stir to dissolve, prepare a solution A with a collagen concentration of 0.05g/L-5.0g/L and place it at 4°C;

2)向A溶液中加入可溶性盐,形成B溶液,使B溶液中可溶性盐的浓度为0.05M~0.3M;2) adding soluble salts to solution A to form solution B, so that the concentration of soluble salts in solution B is 0.05M to 0.3M;

3)调节B溶液的pH值为3.5~5.0,作为电解质溶液;3) adjust the pH value of solution B to 3.5 to 5.0 as the electrolyte solution;

4)在电化学沉积装置中,将医用金属移植体用作阴极,铂为阳极,饱和甘汞电极或氯化银电极为参比电极浸入上述电解质溶液,电解质溶液温度为18℃~50℃,阴极与阳极间工作距离为1cm~20cm;4) In the electrochemical deposition device, the medical metal implant is used as the cathode, the platinum is used as the anode, and the saturated calomel electrode or the silver chloride electrode is used as the reference electrode. The working distance between cathode and anode is 1cm~20cm;

5)采用恒电流或恒电压模式在医用移植体表面电沉积,恒电流模式的电流大小为0.5mA~100mA,恒电压模式的电压为1V~30V,沉积时间为0.25h~24h,反应结束后取出医用金属移植体清洗,干燥后获得表面胶原改性的医用金属移植体。5) Use constant current or constant voltage mode to electrodeposit on the surface of medical implants. The current in constant current mode is 0.5mA-100mA, the voltage in constant voltage mode is 1V-30V, and the deposition time is 0.25h-24h. The medical metal graft body is taken out, cleaned, and dried to obtain a medical metal graft body modified by surface collagen.

本发明中,所说的酸性溶液可以为盐酸或醋酸溶液。所说的可溶性盐可以是氯化钠、硝酸钠、氯化钾或硝酸钾。所说的医用金属移植体可以是钛、钛合金、钴铬钼合金、钴铬合金、医用不锈钢或具有涂层的医用金属移植体。所说的涂层可以是羟基磷灰石涂层、含氟羟基磷灰石涂层或二氧化钛涂层。In the present invention, said acidic solution may be hydrochloric acid or acetic acid solution. Said soluble salt may be sodium chloride, sodium nitrate, potassium chloride or potassium nitrate. Said medical metal implant can be titanium, titanium alloy, cobalt-chromium-molybdenum alloy, cobalt-chromium alloy, medical stainless steel or coated medical metal implant. Said coating may be hydroxyapatite coating, fluorine-containing hydroxyapatite coating or titanium dioxide coating.

本发明采用电化学的方法,在酸性的溶解有胶原蛋白的电解质溶液中,通过电极反应可使医用金属材料周围局部溶液pH值升高,而不影响电解质溶液整体酸性。医用金属材料周围溶液pH值升高使得溶解的胶原凝胶化,即胶原分子自组装成为胶原纤维。本发明通过电极反应形成的局部pH值变化有利于胶原纤维附着于医用金属材料表面,形成胶原纤维层。胶原纤维是细胞外基质的主要成分,本发明对医用金属的表面胶原改性提高了医用金属表面生物活性,有利于细胞的粘附以及组织修复和生长。本发明提供的医用金属材料表面胶原改性方法简单易行,高效,易于产业化。The invention adopts an electrochemical method, and in the acidic electrolyte solution in which collagen is dissolved, the pH value of the local solution around the medical metal material can be increased through electrode reaction without affecting the overall acidity of the electrolyte solution. The pH value of the solution around the medical metal material increases to make the dissolved collagen gel, that is, the collagen molecules self-assemble into collagen fibers. The local pH value change formed by the electrode reaction in the invention is favorable for the collagen fiber to attach to the surface of the medical metal material to form a collagen fiber layer. Collagen fiber is the main component of extracellular matrix. The surface collagen modification of the medical metal improves the biological activity of the medical metal surface, which is beneficial to cell adhesion, tissue repair and growth. The method for modifying collagen on the surface of medical metal materials provided by the invention is simple, easy to implement, highly efficient and easy to industrialize.

附图说明Description of drawings

附图是本发明采用电化学法对钛合金生物材料表面胶原改性的的SEM照片。Accompanying drawing is the SEM photo of the present invention adopting electrochemical method to modify the collagen on the surface of titanium alloy biomaterial.

具体实施方式Detailed ways

以下结合实施例进一步说明本发明。Below in conjunction with embodiment further illustrate the present invention.

实施例1Example 1

将胶原加入盐酸溶液中,盐酸溶液pH值为1,搅拌溶解,配制胶原浓度为5.0g/L的A溶液并置于4℃。向A溶液中加入氯化钠,形成B溶液,使B溶液中氯化钠浓度为0.3M。用氨水溶液调节B溶液的pH值为3.5,作为电解质溶液。在电化学沉积装置中,以医用钛合金移植体为阴极,铂为阳极,饱和甘汞电极为参比电极浸入电解质溶液,电解质溶液温度为18℃,阴极与阳极间工作距离为2cm。采用恒电流模式在医用移植体表面电沉积,电流大小为0.5mA,沉积时间为1h。反应结束后取出医用钛合金移植体清洗,干燥后获得表面胶原改性的医用钛合金移植体。见附图,在钛合金生物材料表面附着胶原纤维层。The collagen was added into the hydrochloric acid solution, the pH value of the hydrochloric acid solution was 1, stirred and dissolved, and a solution A with a collagen concentration of 5.0 g/L was prepared and placed at 4°C. Add sodium chloride to solution A to form solution B, so that the concentration of sodium chloride in solution B is 0.3M. Use ammonia solution to adjust the pH of solution B to 3.5 as the electrolyte solution. In the electrochemical deposition device, the medical titanium alloy implant is used as the cathode, the platinum is used as the anode, and the saturated calomel electrode is used as the reference electrode. Electrodeposition on the surface of medical implants was carried out in a constant current mode with a current of 0.5mA and a deposition time of 1h. After the reaction is finished, the medical titanium alloy implant is taken out for cleaning, and the medical titanium alloy implant with surface collagen modification is obtained after drying. As shown in the attached figure, a collagen fiber layer is attached to the surface of the titanium alloy biomaterial.

实施例2Example 2

将胶原加入醋酸溶液中,醋酸溶液pH值为2,搅拌溶解,配制胶原浓度为1g/L的A溶液并置于4℃。向A溶液中加入硝酸钠,形成B溶液,使B溶液中硝酸钠浓度为0.05M。用氢氧化钠溶液调节B溶液的pH值为4,作为电解质溶液。在电化学沉积装置中,以医用不锈钢移植体为阴极,铂为阳极,氯化银电极为参比电极浸入电解质溶液,电解质溶液温度为18℃,阴极与阳极间工作距离为20cm。采用恒电压模式在医用移植体表面电沉积,电压大小为30V,沉积时间为24h。反应结束后取出医用不锈钢清洗,干燥后获得表面胶原改性的医用不锈钢移植体。Add the collagen into the acetic acid solution, the pH of the acetic acid solution is 2, stir to dissolve, prepare the A solution with a collagen concentration of 1g/L and place it at 4°C. Add sodium nitrate to solution A to form solution B, so that the concentration of sodium nitrate in solution B is 0.05M. Adjust the pH value of solution B to 4 with sodium hydroxide solution as the electrolyte solution. In the electrochemical deposition device, the medical stainless steel implant is used as the cathode, the platinum is used as the anode, and the silver chloride electrode is used as the reference electrode. Electrodeposition was performed on the surface of medical implants in a constant voltage mode, with a voltage of 30V and a deposition time of 24h. After the reaction is finished, the medical stainless steel is taken out for cleaning, and after drying, a medical stainless steel implant with surface collagen modification is obtained.

实施例3Example 3

将胶原加入盐酸溶液中,盐酸溶液pH值为4,搅拌溶解,配制胶原浓度为0.3g/L的A溶液并置于4℃。向A溶液中加入氯化钾,形成B溶液,使B溶液中氯化钾浓度为0.1M。用Tris缓冲溶液调节B溶液的pH值为5,作为电解质溶液。在电化学沉积装置中,以医用钴铬钼合金移植体为阴极,铂为阳极,氯化银电极为参比电极浸入电解质溶液,电解质溶液温度为50℃,阴极与阳极间工作距离为1cm。采用恒电压模式在医用移植体表面电沉积,电压大小为3V,沉积时间为2h。反应结束后取出医用钴铬钼合金移植体清洗,干燥后获得表面胶原改性的医用钴铬钼合金移植体。The collagen was added into the hydrochloric acid solution, the pH value of the hydrochloric acid solution was 4, stirred and dissolved, and a solution A with a collagen concentration of 0.3 g/L was prepared and placed at 4°C. Add potassium chloride to solution A to form solution B, so that the concentration of potassium chloride in solution B is 0.1M. Adjust the pH value of solution B to 5 with Tris buffer solution as the electrolyte solution. In the electrochemical deposition device, the medical cobalt-chromium-molybdenum alloy implant is used as the cathode, the platinum is used as the anode, and the silver chloride electrode is used as the reference electrode. Electrodeposition on the surface of medical implants is carried out in a constant voltage mode with a voltage of 3V and a deposition time of 2h. After the reaction is finished, the medical cobalt-chromium-molybdenum alloy implant is taken out for cleaning, and the medical cobalt-chromium-molybdenum alloy implant with surface collagen modification is obtained after drying.

实施例4Example 4

将胶原加入醋酸溶液中,醋酸溶液pH值为2,搅拌溶解,配制胶原浓度为0.5g/L的A溶液并置于4℃。向A溶液中加入硝酸钾,形成B溶液,使B溶液中硝酸钾浓度为0.2M。用氢氧化钾溶液调节B溶液的pH值为4.5,作为电解质溶液。在电化学沉积装置中,以医用具有含氟羟基磷灰石涂层金属移植体为阴极,铂为阳极,饱和甘汞电极为参比电极浸入电解质溶液,电解质溶液温度为40℃,阴极与阳极间工作距离为2.5cm。采用恒电流模式在医用移植体表面电沉积,电流大小为10mA,沉积时间为4h。反应结束后取出医用移植体清洗,干燥后获得表面胶原改性的医用金属移植体。Add the collagen into the acetic acid solution, the pH of the acetic acid solution is 2, stir to dissolve, prepare the A solution with a collagen concentration of 0.5g/L and place it at 4°C. Add potassium nitrate to solution A to form solution B, so that the concentration of potassium nitrate in solution B is 0.2M. Adjust the pH value of solution B to 4.5 with potassium hydroxide solution as the electrolyte solution. In the electrochemical deposition device, the medical implant with fluorine-containing hydroxyapatite coating is used as the cathode, the platinum is used as the anode, and the saturated calomel electrode is used as the reference electrode. The working distance between them is 2.5cm. Electrodeposition was performed on the surface of medical implants in constant current mode, with a current of 10mA and a deposition time of 4h. After the reaction is finished, the medical implant is taken out for cleaning, and the surface collagen-modified medical metal implant is obtained after drying.

Claims (5)

1. electrochemical process is characterized in that the method for collagen modification of medical metal implant surface: may further comprise the steps:
1) collagen being added pH value is in 1~4 the acid solution, stirring and dissolving, and the preparation collagen concentration is the A solution of 0.05g/L~5.0g/L and places under 4 ℃;
2) add soluble-salt in A solution, form B solution, the concentration that makes soluble-salt in the B solution is 0.05 M~0.3M;
3) pH value of adjusting B solution is 3.5~5.0, as electrolyte solution;
4) in electrochemical depositer, as negative electrode, platinum is anode with medical metal implant, and saturated calomel electrode or silver chloride electrode are that reference electrode immerses above-mentioned electrolyte solution, the electrolyte solution temperature is 18 ℃~50 ℃, and operating distance is 1cm~20cm between negative electrode and anode;
5) adopt constant current or constant voltage mode to deposit in the medical transplant surface electrical, the size of current of constant current mode is 0.5mA~100mA, the voltage of constant voltage mode is 1V~30V, sedimentation time is 0.25h~24h, reaction finishes the back and takes out the medical metal implant cleaning, and dry back obtains the medical metal implant of surface collagen modification.
2. electrochemical process according to claim 1 is characterized in that to the method for collagen modification of medical metal implant surface said acid solution is hydrochloric acid or acetum.
3. electrochemical process according to claim 1 is characterized in that to the method for collagen modification of medical metal implant surface said soluble-salt is sodium chloride, Chile saltpeter, potassium chloride or potassium nitrate.
4. electrochemical process according to claim 1 is characterized in that to the method for collagen modification of medical metal implant surface said medical metal implant is the medical metal implant of titanium, titanium alloy, vitallium, cochrome, medical stainless steel or biologically active coating.
5. electrochemical process according to claim 4 is characterized in that to the method for collagen modification of medical metal implant surface said bioactivity coatings is hydroxyapatite coating layer, fluoridated hydroxyapatite coating or coating of titanium dioxide.
CNA2007101565517A 2007-11-08 2007-11-08 Method for modifying medical metallic grafting body surface collagen by galvano-chemistry method Pending CN101161295A (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103041976A (en) * 2012-12-25 2013-04-17 苏州大学附属第二医院 Method for preparing argentiferous antibacterial coating on surface of CoCr alloy material for oral use
CN110331124A (en) * 2019-06-14 2019-10-15 浙江大学 A kind of electric polypyrrole/extracellular matrix laminated film and preparation method thereof
CN114808081A (en) * 2022-01-27 2022-07-29 华东理工大学 Short-distance oriented amorphous collagen material capable of being stripped from electrode and electrochemical preparation method thereof
CN115233246A (en) * 2022-01-27 2022-10-25 华东理工大学 Tough collagen bandage material, and preparation method and application thereof
CN115518206A (en) * 2022-10-18 2022-12-27 华中科技大学同济医学院附属协和医院 Self-mineralized GBR film and preparation method thereof
WO2023142599A1 (en) * 2022-01-27 2023-08-03 华东理工大学 Preparation method for collagen material stripped from electrode, and use of collagen material

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103041976A (en) * 2012-12-25 2013-04-17 苏州大学附属第二医院 Method for preparing argentiferous antibacterial coating on surface of CoCr alloy material for oral use
CN103041976B (en) * 2012-12-25 2014-04-30 苏州大学附属第二医院 Method for preparing argentiferous antibacterial coating on surface of CoCr alloy material for oral use
CN110331124A (en) * 2019-06-14 2019-10-15 浙江大学 A kind of electric polypyrrole/extracellular matrix laminated film and preparation method thereof
CN110331124B (en) * 2019-06-14 2022-03-22 浙江大学 Conductive polypyrrole/extracellular matrix composite film and preparation method thereof
CN114808081A (en) * 2022-01-27 2022-07-29 华东理工大学 Short-distance oriented amorphous collagen material capable of being stripped from electrode and electrochemical preparation method thereof
CN115233246A (en) * 2022-01-27 2022-10-25 华东理工大学 Tough collagen bandage material, and preparation method and application thereof
WO2023142599A1 (en) * 2022-01-27 2023-08-03 华东理工大学 Preparation method for collagen material stripped from electrode, and use of collagen material
CN114808081B (en) * 2022-01-27 2024-10-25 江苏博创生物科技有限公司 Short-range oriented amorphous collagen material capable of being peeled off from electrode and electrochemical preparation method thereof
CN115233246B (en) * 2022-01-27 2025-09-30 华东理工大学 A strong collagen bandage material, preparation method and application thereof
CN115518206A (en) * 2022-10-18 2022-12-27 华中科技大学同济医学院附属协和医院 Self-mineralized GBR film and preparation method thereof
CN115518206B (en) * 2022-10-18 2024-01-23 华中科技大学同济医学院附属协和医院 Self-mineralizing GBR membrane and preparation method thereof

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