CN115381569A - PEEK Implant Surface Improvement Method and Equipment - Google Patents

Abstract

Translated fromChinese

本发明公开了一种PEEK种植体表面改进方法和设备，改性方法包括以下步骤：制成磺化PEEK步骤、制成SPEEK‑H步骤、制成SPEEK‑NH2步骤、制成SPEEK‑CS步骤，及制成SPEEK‑CS@Mg步骤：将SPEEK‑CS料浸入Mg(OH)2溶液中，磁力搅拌；之后从反应溶液中取出SPEEK‑CS料，用去离子水洗涤，再干燥而成。本发明方法基于PEEK与乙二胺的席夫碱反应和EDA与CS的酰胺化反应，将硫酸软骨素镁引入磺化PEEK表面。本发明的成品植入体表面具有三维微孔结构和良好的亲水性，并能释放镁离子。SPEEK‑CS@Mg能显著促进细胞黏附和扩散，提高成骨活性和血管生成活性，减轻炎症反应。

The invention discloses a method and equipment for improving the surface of a PEEK implant. The modification method comprises the following steps: making sulfonated PEEK, making SPEEK-H, making SPEEK-NH2, and making SPEEK-CS, And the steps of making SPEEK‑CS@Mg: immerse the SPEEK‑CS material in the Mg(OH)2 solution and stir it magnetically; then take out the SPEEK‑CS material from the reaction solution, wash it with deionized water, and then dry it. The method of the invention is based on the Schiff base reaction of PEEK and ethylenediamine and the amidation reaction of EDA and CS, and introduces magnesium chondroitin sulfate to the surface of sulfonated PEEK. The surface of the finished implant of the invention has a three-dimensional microporous structure and good hydrophilicity, and can release magnesium ions. SPEEK‑CS@Mg can significantly promote cell adhesion and spreading, enhance osteogenic activity and angiogenic activity, and reduce inflammatory response.

Description

Translated fromChinese

PEEK种植体表面改进方法和设备PEEK Implant Surface Improvement Method and Equipment

技术领域technical field

本发明涉及种植体表面改进方法，尤其涉及一种PEEK种植体表面改进方法和设备。The invention relates to a method for improving the surface of an implant, in particular to a method and equipment for improving the surface of a PEEK implant.

背景技术Background technique

聚醚醚酮(PEEK)是一种骨科植入式生物材料，于20世纪90年代正式获得美国FDA批准。PEEK由于具有良好的力学性能、良好的生物相容性和优良的耐化学性，被认为是骨科中最有前途的植入材料之一。不幸的是，PEEK的生物惰性导致其植入前后骨结合不足，严重限制了其在骨科中的应用。因此，对PEEK进行表面改性成为引入PEEK正性生物特性的主要解决方案之一，目的是进一步扩大其在骨科中的应用。目前，关于PEEK表面改性的研究大多集中在增强成骨作用方面。然而，骨整合是骨组织与植入之间的一个综合性生理过程，骨整合过程中的各种问题，特别是炎症反应和血管生成都应充分考虑。众所周知，植入的生物材料在体内会引发强烈的异物反应，导致慢性炎症。研究表明，持续的炎症反应不仅延长了骨组织修复的时间，而且诱导种植体周围纤维包裹的形成，最终导致种植体失败。此外，血管再生是植入物长期成骨固定的另一个关键因素。骨缺损部位良好的血管生成可以为组织再生提供必要的氧气和营养物质，这对种植体的固定非常有利。虽然已经取得了一些有希望的进展，但目前具有抗炎、血管生成和成骨特性的PEEK植入物仍然很少。因此，迫切需要通过表面修饰来改善PEEK的抗炎、血管生成、成骨性能。硫酸软骨素(CS)是一种天然的糖胺聚糖，广泛存在于动脉血、肌腱、软骨等人体软组织中，是细胞外基质(ECM)的主要成分之一。研究证明硫酸软骨素具有抗炎和成骨活性。本发明人为此提出一种PEEK种植体表面改进方法及快速实现PEEK种植体表面改进的设备。Polyetheretherketone (PEEK) is an orthopedic implant biomaterial that was officially approved by the US FDA in the 1990s. PEEK is considered to be one of the most promising implant materials in orthopedics due to its good mechanical properties, good biocompatibility, and excellent chemical resistance. Unfortunately, the bioinertness of PEEK leads to insufficient osseointegration before and after implantation, severely limiting its use in orthopedics. Therefore, surface modification of PEEK has become one of the main solutions to introduce positive biological properties of PEEK, with the aim of further expanding its application in orthopedics. At present, most of the research on PEEK surface modification focuses on enhancing osteogenesis. However, osseointegration is a comprehensive physiological process between bone tissue and implantation, and various problems in the process of osseointegration, especially inflammatory response and angiogenesis should be fully considered. Implanted biomaterials are known to trigger a strong foreign body response in the body, leading to chronic inflammation. Studies have shown that the continuous inflammatory response not only prolongs the time of bone tissue repair, but also induces the formation of fibrous packages around implants, which eventually leads to implant failure. Furthermore, vascular regeneration is another key factor for long-term osteogenic fixation of implants. Good angiogenesis in the bone defect site can provide the necessary oxygen and nutrients for tissue regeneration, which is very beneficial to the fixation of the implant. Although some promising progress has been made, there are still few PEEK implants with anti-inflammatory, angiogenic and osteogenic properties. Therefore, there is an urgent need to improve the anti-inflammatory, angiogenic, and osteogenic properties of PEEK through surface modification. Chondroitin sulfate (CS) is a natural glycosaminoglycan, which widely exists in arterial blood, tendon, cartilage and other human soft tissues, and is one of the main components of extracellular matrix (ECM). Research has demonstrated that chondroitin sulfate has anti-inflammatory and osteogenic activity. Therefore, the inventor proposes a method for improving the surface of PEEK implants and a device for quickly realizing the surface improvement of PEEK implants.

发明内容Contents of the invention

本发明的目的是针对现有技术中存在的上述问题，本发明提供一种PEEK种植体表面改进方法和设备。The object of the present invention is to solve the above-mentioned problems existing in the prior art, and the present invention provides a method and equipment for improving the surface of a PEEK implant.

本发明的目的通过下列技术方案来实现：The purpose of the present invention is achieved through the following technical solutions:

本发明PEEK种植体表面改性方法，包括以下步骤：The PEEK implant surface modification method of the present invention comprises the following steps:

(a)提供PEEK基材；(a) Provide PEEK substrate;

(b)将PEEK基材浸渍于浓硫酸溶液中，去除所述浓硫酸溶液的溶剂，得到磺化PEEK料；(b) immersing the PEEK substrate in a concentrated sulfuric acid solution, removing the solvent of the concentrated sulfuric acid solution to obtain a sulfonated PEEK material;

(c)将所述磺化PEEK料进行水热处理反应，得到SPEEK-H料；(c) subjecting the sulfonated PEEK material to a hydrothermal treatment reaction to obtain a SPEEK-H material;

(d)将所述SPEEK-H料置入装有乙二胺EDA的容器中反应获得SPEEK-NH2料：(d) put the SPEEK-H material into a container equipped with ethylenediamine EDA and react to obtain SPEEK-NH Material:

(e)将所述SPEEK-NH2料添加到含硫酸软骨素的预制备溶液中混合，去除所述含硫酸软骨素的预制备溶液的溶剂，得到SPEEK-CS料；(e) adding the SPEEK-NH2 material to the pre-prepared solution containing chondroitin sulfate and mixing, removing the solvent of the pre-prepared solution containing chondroitin sulfate to obtain the SPEEK-CS material;

(f)将所述SPEEK-CS料浸渍于氢氧化镁溶液中，去除所述氢氧化镁溶液的溶剂，洗涤干燥后得到SPEEK-CS@Mg。(f) immerse the SPEEK-CS material in a magnesium hydroxide solution, remove the solvent of the magnesium hydroxide solution, wash and dry to obtain SPEEK-CS@Mg.

在其中一些实施例中，制成磺化PEEK料步骤：将医用级PEEK基材依次用丙酮、无水乙醇、去离子水在超声波条件下进行清洗；然后将这些PEEK基材放入55-65℃的恒温下进行干燥；再将PEEK基材浸入浓度大于90％的浓硫酸中，在23-28℃的温度下进行超声波处理，得到磺化PEEK料；In some of these embodiments, the step of making sulfonated PEEK materials: the medical-grade PEEK substrates are sequentially cleaned with acetone, absolute ethanol, and deionized water under ultrasonic conditions; then these PEEK substrates are placed in a 55-65 Dry at a constant temperature of °C; then immerse the PEEK substrate in concentrated sulfuric acid with a concentration greater than 90%, and perform ultrasonic treatment at a temperature of 23-28°C to obtain a sulfonated PEEK material;

在其中一些实施例中，制成SPEEK-H料步骤：将磺化PEEK料从浓硫酸中取出，放入超纯水中，在超声波条件下浸泡和清洗；再将磺化PEEK料在85-95℃的超纯水中浸泡8-15小时，以进行水热处理，得到的PEEK料命名为SPEEK-H料；In some of these embodiments, the step of making the SPEEK-H material is: take the sulfonated PEEK material out of the concentrated sulfuric acid, put it into ultrapure water, soak and clean it under ultrasonic conditions; then put the sulfonated PEEK material at 85- Soak in ultra-pure water at 95°C for 8-15 hours for hydrothermal treatment, and the obtained PEEK material is named SPEEK-H material;

在其中一些实施例中，制成SPEEK-NH2料步骤：将SPEEK-H料放入装有乙二胺EDA的容器中，并加热至120-135℃之间并在回流冷凝模式下保持3-5h；反应完成后，用去离子水去除SPEEK-H料表面未反应的残余乙二胺EDA；随后用异丙醇、去离子水分别超声波处理冲洗8-13min，然后在55-63℃干燥0.8-2h，得到的材料命名为SPEEK-NH2料；In some of these embodiments, the step of making SPEEK-NH2 material: put the SPEEK-H material into a container filled with ethylenediamine EDA, and heat it to between 120-135 ° C and keep it in the reflux condensation mode for 3- 5h; After the reaction is completed, remove the unreacted residual ethylenediamine EDA on the surface of the SPEEK-H material with deionized water; then use isopropanol and deionized water to ultrasonically rinse for 8-13min, and then dry at 55-63°C for 0.8 -2h, the obtained material is named as SPEEK-NH2 material;

在其中一些实施例中，制成SPEEK-CS料步骤：将SPEEK-NH2料添加到含有40％(v/v)乙醇、MES(PH＝5.0)、0.01g/mL硫酸软骨素、EDC和NHS的预制备溶液中在23-27℃下磁力搅拌10-13h；再将制备好的材料用去离子水冲洗，命名为SPEEK-CS料；制成SPEEK-CS@Mg步骤：将SPEEK-CS料浸入Mg(OH)2溶液中，在23-27℃下磁力搅拌3-5h；化学反应完成后，从反应溶液中取出SPEEK-CS料，用去离子水洗涤3次，再于35-39℃下干燥1-3h后，记为SPEEK-CS@Mg。In some of these embodiments, the step of making SPEEK-CS material: adding SPEEK-NH2 material to a mixture containing 40% (v/v) ethanol, MES (PH=5.0), 0.01g/mL chondroitin sulfate, EDC and NHS Stir magnetically at 23-27°C for 10-13h in the pre-prepared solution; then rinse the prepared material with deionized water and name it SPEEK-CS material; the steps of making SPEEK-CS@Mg: make SPEEK-CS material Immerse in the Mg(OH)2 solution, stir magnetically at 23-27°C for 3-5h; after the chemical reaction is complete, take out the SPEEK-CS material from the reaction solution, wash it with deionized water After drying for 1-3 hours, it is recorded as SPEEK-CS@Mg.

在其中一些实施例中，制成磺化PEEK步骤中，采用气泵进行干燥，恒温干燥时间为40-80分钟；在23-28℃的温度下进行超声波的时间为2-5分钟；制成SPEEK-H步骤中的在超声波条件下浸泡和清洗的时间为8-15分钟。In some of these embodiments, in the step of making sulfonated PEEK, an air pump is used for drying, and the drying time at a constant temperature is 40-80 minutes; the time for ultrasonication at a temperature of 23-28°C is 2-5 minutes; to make SPEEK - The soaking and cleaning time under ultrasonic conditions in the H step is 8-15 minutes.

在其中一些实施例中，还包括设于制成磺化PEEK步骤之前的PEEK基材预制步骤，根据接收到的需求3D图形生成模具，采用PEEK母粒进行模具成形，或者利用PEEK母材进行3D加工，制成PEEK基材。In some of these embodiments, it also includes a PEEK base material prefabrication step before the step of making sulfonated PEEK, generating a mold according to the received demand 3D graphics, using PEEK masterbatch for mold forming, or using PEEK base material for 3D Processing to make PEEK substrate.

在其中一些实施例中，还包括用于容纳PEEK基材的镂空治具，所述镂空治具包括带有内空腔的镂空部，设于镂空部上方的联接部。本发明用于PEEK种植体表面改性的设备，包括基座，设于基座上的若干个工位；还包括设于基座上的直形或环形的导轨，及与所述导轨滑动联接的滑座，用于驱动所述滑座的驱动机构；所述滑座设有升降机构，以升降镂空治具；需要加工的PEEK基材置于所述镂空治具内。In some of the embodiments, a hollowing jig for accommodating the PEEK substrate is also included, and the hollowing jig includes a hollowed out part with an inner cavity, and a coupling part arranged above the hollowed out part. The present invention is used for the equipment of PEEK implant surface modification, comprises base, is arranged on several stations on the base; Also comprises the guide rail that is arranged on the base or circular, and slides with described guide rail The sliding seat is used to drive the driving mechanism of the sliding seat; the sliding seat is provided with a lifting mechanism to lift the hollow jig; the PEEK base material to be processed is placed in the hollow jig.

在其中一些实施例中，所述工位包括丙酮清洗工位、无水乙醇清洗工位、去离子水清洗工位一、第一恒温干燥工位、硫酸超声波工位、超纯水超声波工位、超纯水水热工位、乙二胺EDA工位、去离子水清洗工位二、异丙醇冲洗工位、去离子水冲洗工位、第二恒温干燥工位、第一磁力搅拌工位、第二磁力搅拌工位、第三恒温干燥工位。In some of these embodiments, the stations include acetone cleaning station, absolute ethanol cleaning station, deionized water cleaning station one, the first constant temperature drying station, sulfuric acid ultrasonic station, ultrapure water ultrasonic station , ultrapure water hydrothermal station, ethylenediamine EDA station, deionized water cleaning station 2, isopropanol rinsing station, deionized water rinsing station, second constant temperature drying station, first magnetic stirrer position, the second magnetic stirring station, and the third constant temperature drying station.

在其中一些实施例中，所述升降机构的下端设有磁性联接座，及设于所述磁性联接座的联接孔；所述镂空治具的上端设有导磁件，以磁性联接于所述联接孔。In some of these embodiments, the lower end of the lifting mechanism is provided with a magnetic connection seat, and a connection hole is provided in the magnetic connection seat; the upper end of the hollow jig is provided with a magnetic guide to magnetically connect Connection hole.

在其中一些实施例中，所述升降机构为电缸，还包括设于所述电缸与所述磁性联接座之间的超声波发生器。优选地，所述镂空治具设有平形或球形的底部，以及开口斜向上的入料口；所述镂空治具表面设有聚四氟乙烯涂层。In some of the embodiments, the lifting mechanism is an electric cylinder, and further includes an ultrasonic generator disposed between the electric cylinder and the magnetic coupling seat. Preferably, the hollowed out jig has a flat or spherical bottom, and a material inlet opening obliquely upward; the surface of the hollowed out jig is provided with a polytetrafluoroethylene coating.

在其中一些实施例中，所述镂空治具设有上挡板，用于与各个工位的上开口形成密封联接；所述上挡板的外侧面设有斜向下的导向斜面，以快速与各个工位的上开口形成密封联接。本发明还公开了一种可以用于容纳PEEK基材、也可以用于其它液体磁力搅拌的镂空治具，镂空治具包括带有内空腔的镂空部，设于镂空部上方的联接部。In some of these embodiments, the hollow fixture is provided with an upper baffle, which is used to form a sealed connection with the upper openings of each station; It forms a sealed connection with the upper opening of each station. The invention also discloses a hollowed-out jig which can be used for accommodating PEEK substrates and magnetic stirring for other liquids. The hollowed-out jig includes a hollowed out part with an inner cavity and a coupling part arranged above the hollowed out part.

在其中一些实施例中，在镂空治具的底部设有由小变大的螺旋状通槽(顺时针或逆时针)。优选地，镂空治具的底部为圆盘状，且中心位置向上凸起，使得PEEK基材之类的工件放入治具内里，会尽量分布于四周的位置，这样的结构，使得镂空治具在磁力搅拌工位时，PEEK基材之类的工件会远离旋转中心，处于流速较高的区域，能获得更好的搅拌效果。In some of the embodiments, a spiral channel (clockwise or counterclockwise) is provided at the bottom of the hollow jig. Preferably, the bottom of the hollowed-out jig is disc-shaped, and the central position protrudes upwards, so that workpieces such as PEEK substrates are placed in the jig and will be distributed as far as possible around the position. Such a structure makes the hollowed-out jig In the magnetic stirring station, workpieces such as PEEK substrates will be far away from the center of rotation, and will be in the area of higher flow rate, which can obtain better stirring effect.

与现有技术相比，本发明的有益效果为：本发明PEEK种植体表面改性方法基于PEEK与乙二胺(EDA)的席夫碱反应和EDA与CS的酰胺化反应，将硫酸软骨素镁引入磺化PEEK(SPEEK-CS@Mg)表面。SPEEK-CS@Mg植入体表面具有三维微孔结构和良好的亲水性，并能释放镁离子。体外细胞实验表明SPEEK-CS@Mg具有良好的生物相容性和安全性。而且，与原来的PEEK相比，SPEEK-CS@Mg能显著促进细胞黏附和扩散，提高成骨活性和血管生成活性，减轻炎症反应。动物实验进一步证实SPEEK-CS@Mg有利于PEEK材料的成骨和成骨固定。因此，我们通过一种经济、简单、可重复、可行的方法，利用硫酸软骨素镁对PEEK材料进行表面改性，实现了良好的预期，将拓宽PEEK材料在骨科植入物中的应用。Compared with the prior art, the beneficial effect of the present invention is: the PEEK implant surface modification method of the present invention is based on the Schiff base reaction of PEEK and ethylenediamine (EDA) and the amidation reaction of EDA and CS, and the chondroitin sulfate Magnesium was introduced into the surface of sulfonated PEEK (SPEEK-CS@Mg). The surface of SPEEK-CS@Mg implant has a three-dimensional microporous structure and good hydrophilicity, and can release magnesium ions. In vitro cell experiments showed that SPEEK-CS@Mg has good biocompatibility and safety. Moreover, compared with the original PEEK, SPEEK-CS@Mg can significantly promote cell adhesion and spreading, enhance osteogenic activity and angiogenic activity, and reduce inflammatory response. Animal experiments further confirmed that SPEEK-CS@Mg is beneficial to the osteogenesis and osteogenic fixation of PEEK materials. Therefore, our surface modification of PEEK material with magnesium chondroitin sulfate through an economical, simple, reproducible, and feasible method has achieved good expectations and will broaden the application of PEEK material in orthopedic implants.

本发明设备则通过与导轨滑动联接的滑座，将PEEK基材放在滑座下方的镂空治具内，实现在不同工位之间移动，实现自动化的操作，减少人员操作的成本和失误。因为本发明的产品尺寸较小，一般用于骨科植入物，且因为使用的形状不一，属于单件小批量生产。因此，各个工位的设备，可以由实验室设备组合而成，经过必要的动力机构的组合即可实现，这样的结构成本低，易操作，且易维护。The equipment of the present invention puts the PEEK base material in the hollow jig under the sliding seat through the sliding seat slidingly connected with the guide rail, so as to realize the movement between different stations, realize the automatic operation, and reduce the cost and error of personnel operation. Because the size of the product of the present invention is small, it is generally used for orthopedic implants, and because the shapes used are different, it belongs to single-piece small-batch production. Therefore, the equipment of each station can be combined by laboratory equipment, and can be realized through the combination of necessary power mechanisms. Such a structure is low in cost, easy to operate, and easy to maintain.

附图说明Description of drawings

图1为本发明PEEK种植体表面改进方法具体实施例的步骤示意图；Fig. 1 is the step schematic diagram of the specific embodiment of PEEK implant surface improvement method of the present invention;

图2为本发明实施例中PEEK种植体表面改进方法具体实施例的光谱图(A部分：CS、PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS，SPEEK-CS@Mg的ATR-FTIR光谱图；B部分：PEEK、SPEEK-H、SPEEK-NH2的光谱，SPEEK-CS，SPEEK-CS@Mg的XPS光谱图；C部分：不同样品表面重要元素的高分辨率XPS光谱图)；Fig. 2 is the spectrogram (part A: CS, PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS, the ATR-FTIR spectrum of SPEEK-CS@Mg of the specific embodiment of PEEK implant surface improvement method in the embodiment of the present invention Figure; Part B: Spectra of PEEK, SPEEK-H, SPEEK-NH2, XPS spectra of SPEEK-CS, SPEEK-CS@Mg; Part C: High-resolution XPS spectra of important elements on different sample surfaces);

图3为本发明实施例中PEEK种植体表面改进方法具体实施例的SEM照片和元素图【(A)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的SEM照片；(B)部分为：SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的元素图】；Fig. 3 is the SEM photo and element map of the specific embodiment of the PEEK implant surface improvement method in the embodiment of the present invention [(A) part is: PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg SEM photo; part (B) is: elemental map of SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg];

图4为本发明实施例中PEEK种植体表面改进方法具体实施例的水接触图【(A)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的水接触角示意图，每组n＝为3；(B)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的水接触角坐标图，每组n＝为3；(C)部分为：SPEEK-CS@Mg样品中1～15天的Mg离子的累积释放曲线】；Fig. 4 is the water contact diagram of the specific embodiment of the PEEK implant surface improvement method in the embodiment of the present invention [(A) part is: water contact of PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg Angle schematic diagram, n=3 for each group; part (B) is: water contact angle coordinate diagram of PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg, n=3 for each group; ( Part C) is: the cumulative release curve of Mg ions in the SPEEK-CS@Mg sample for 1 to 15 days];

图5为本发明用于PEEK种植体表面改性的设备具体实施例一的平面示意图；Fig. 5 is the schematic plan view of thespecific embodiment 1 of the equipment for PEEK implant surface modification of the present invention;

图6为本发明用于PEEK种植体表面改性的设备具体实施例二的平面示意图；Fig. 6 is a schematic plan view of a second embodiment of the device for surface modification of PEEK implants according to the present invention;

图7为本发明用于PEEK种植体表面改性的设备具体实施例三的滑座和镂空治具的中心位置的剖视图；Fig. 7 is a cross-sectional view of the central position of the sliding seat and hollow jig of the third embodiment of the device for surface modification of PEEK implants according to the present invention;

图8为图7实施例的电路方框图。FIG. 8 is a circuit block diagram of the embodiment in FIG. 7 .

附图标记：10导轨；20滑座；21滑轨电机；30镂空治具；301导磁件；306导向斜面；307上挡板；308入料口；309底部；31磁性联接座；311联接孔；32电缸；33超声波发生器；51水热转盘；52乙二胺转盘；53第一磁力转盘；54第二磁力转盘；80控制器；81工位到达传感器；82工位待机传感器；90PEEK基材；101丙酮清洗工位；102无水乙醇清洗工位；103去离子水清洗工位一；104第一恒温干燥工位；105硫酸超声波工位；106超纯水超声波工位；107超纯水水热工位；108乙二胺EDA工位；109去离子水清洗工位二；110异丙醇冲洗工位；111去离子水冲洗工位；112第二恒温干燥工位；113第一磁力搅拌工位；114第二磁力搅拌工位；115第三恒温干燥工位。Reference signs: 10 guide rail; 20 slide seat; 21 slide rail motor; 30 hollow out jig; 301 magnetic guide; 306 guide slope; 307 upper baffle; Hole; 32 electric cylinder; 33 ultrasonic generator; 51 hydrothermal turntable; 52 ethylenediamine turntable; 53 first magnetic turntable; 54 second magnetic turntable; 80 controller; 81 position arrival sensor; 82 position standby sensor; 90PEEK base material; 101 Acetone cleaning station; 102 Anhydrous ethanol cleaning station; 103 Deionized water cleaning station one; 104 The first constant temperature drying station; 105 Sulfuric acid ultrasonic station; 106 Ultrapure water ultrasonic station; 107 Ultrapure water hydrothermal station; 108 ethylenediamine EDA station; 109 deionized water cleaning station two; 110 isopropanol rinse station; 111 deionized water rinse station; 112 second constant temperature drying station; 113 The first magnetic stirring station; 114 the second magnetic stirring station; 115 the third constant temperature drying station.

具体实施方式Detailed ways

下面将通过以下实施例进行清楚、完整地描述本发明的技术方案中显然，以下将描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。应当理解，当在本说明书和所附权利要求书中使用时，术语“包括”和“包含”指示所描述特征、整体、步骤、操作、元素和/或组件的存在，但并不排除一个或多个其它特征、整体、步骤、操作、元素、组件和/或其集合的存在或添加。还应当理解，在此本发明实施例说明书中所使用的术语仅仅是出于描述特定实施例的目的而并不意在限制本发明实施例。如在本发明实施例说明书和所附权利要求书中所使用的那样，除非上下文清楚地指明其它情况，否则单数形式的“一”、“一个”及“该”意在包括复数形式。The following examples will be used to clearly and completely describe the technical solution of the present invention. Obviously, the examples described below are only some of the examples of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without creative efforts fall within the protection scope of the present invention. It should be understood that when used in this specification and the appended claims, the terms "comprising" and "comprises" indicate the presence of described features, integers, steps, operations, elements and/or components, but do not exclude one or Presence or addition of multiple other features, integers, steps, operations, elements, components and/or collections thereof. It should also be understood that the terms used in the description of the embodiments of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the embodiments of the present invention. As used in the description of the embodiments of the present invention and the appended claims, the singular forms "a", "an" and "the" are intended to include plural forms unless the context clearly dictates otherwise.

如图1所示，为本发明PEEK种植体表面改性方法的步骤，首先利用浓硫酸的蚀刻处理，构建了一个表面具有三维(3D)多孔网络结构的磺化PEEK(SPEEK)。然后，采用水热处理来降低残留酸的细胞毒性；随后，根据PEEK与乙二胺(EDA)的裂夫碱反应和PEEK与CS的酰胺化反应，将硫酸软骨素接枝到SPEEK样品表面；随后，我们利用Mg离子与硫酸软骨素(CS)之间的螯合效应，将Mg引入SPEEK-CS样品的表面，形成SPEEK-CS@Mg样品。As shown in Figure 1, it is the steps of the PEEK implant surface modification method of the present invention. Firstly, a sulfonated PEEK (SPEEK) with a three-dimensional (3D) porous network structure on the surface is constructed by etching with concentrated sulfuric acid. Then, hydrothermal treatment was used to reduce the cytotoxicity of residual acid; subsequently, chondroitin sulfate was grafted onto the surface of SPEEK samples according to the schizophrenia reaction of PEEK with ethylenediamine (EDA) and the amidation reaction of PEEK with CS; , we took advantage of the chelation effect between Mg ions and chondroitin sulfate (CS) to introduce Mg into the surface of SPEEK-CS samples to form SPEEK-CS@Mg samples.

实施例一：Embodiment one:

将医用级PEEK样品依次用丙酮、无水乙醇和去离子(DI)水在超声波条件下每步清洗10分钟，然后将这些样品用空气泵干燥并放入60℃的恒温干燥箱中1小时。之后，将PEEK样品浸入98％的浓硫酸中，在25℃超声处理3min，得到磺化PEEK。随后，除去浓硫酸，加入5mL超纯水，在超声波条件下两次浸泡清洗样品10分钟。将磺化的PEEK样品在90℃的超纯水中浸泡12小时进行水热处理，得到的PEEK样品命名为SPEEK-H；Medical-grade PEEK samples were sequentially cleaned with acetone, absolute ethanol, and deionized (DI) water under ultrasonic conditions for 10 minutes each step, and then these samples were dried with an air pump and placed in a constant temperature drying oven at 60 °C for 1 hour. Afterwards, the PEEK sample was immersed in 98% concentrated sulfuric acid and ultrasonically treated at 25° C. for 3 min to obtain sulfonated PEEK. Subsequently, the concentrated sulfuric acid was removed, 5 mL of ultrapure water was added, and the sample was soaked twice for 10 minutes under ultrasonic conditions. The sulfonated PEEK sample was soaked in ultrapure water at 90°C for 12 hours for hydrothermal treatment, and the obtained PEEK sample was named SPEEK-H;

为了制备CS改性多孔PEEK(SPEEK-CS)，选择乙二胺EDA作为中间分子，在SPEEK-H表面化学接枝硫酸软骨素。简而言之，将60片SPEEK-H样品放入装有60mLEDA的圆底烧瓶中，将系统加热至125℃并在回流冷凝模式下保持4h。反应完成后，用去离子水去除材料表面未反应的残余乙二胺，随后用异丙醇和去离子水在超声处理下连续冲洗试样10min，然后在60℃干燥1h(命名为SPEEK-NH2)。随后，根据我们以往的研究制备了硫酸软骨素酸。然后，将SPEEK-NH2样品添加到含有40％v/v乙醇、50mMMES(PH＝5.0)、0.01g/mL硫酸软骨素酸、40mMEDC和16mMNHS的预制备溶液(每片/1mL)中在25℃下磁力搅拌12h。将制备好的样品用去离子水冲洗3次，命名为SPEEK-CS；In order to prepare CS-modified porous PEEK (SPEEK-CS), ethylenediamine EDA was selected as the intermediate molecule, and chondroitin sulfate was chemically grafted on the surface of SPEEK-H. Briefly, 60 pieces of SPEEK-H samples were put into a round-bottomed flask filled with 60 mL of LEDA, and the system was heated to 125 °C and kept in reflux condensation mode for 4 h. After the reaction was completed, the unreacted residual ethylenediamine on the surface of the material was removed with deionized water, and then the sample was continuously rinsed with isopropanol and deionized water under ultrasonic treatment for 10 min, and then dried at 60°C for 1 h (named SPEEK-NH2) . Subsequently, chondroitin sulfate acid was prepared according to our previous study. Then, the SPEEK-NH2 samples were added to a pre-prepared solution (per tablet/1 mL) containing 40% v/v ethanol, 50 mMMES (PH=5.0), 0.01 g/mL chondroitin sulfate acid, 40 mMEDC, and 16 mM NHS at 25 °C Under magnetic stirring for 12h. The prepared sample was washed 3 times with deionized water, named SPEEK-CS;

最后，将SPEEK-CS材料浸入20mMMg(OH)2溶液(每片/1mL)中，在25℃下磁力搅拌4h。化学反应完成后，从反应溶液中取出样品，用去离子水洗涤3次。所得试样在37℃下干燥2h备用，记为SPEEK-CS@Mg。Finally, the SPEEK-CS material was immersed in 20 mM Mg(OH)2 solution (per tablet/1 mL), and magnetically stirred at 25 °C for 4 h. After the chemical reaction was completed, the samples were taken out from the reaction solution and washed 3 times with deionized water. The obtained sample was dried at 37°C for 2 h for later use, and was designated as SPEEK-CS@Mg.

需要进一步说明的是：What needs to be further explained is:

图2的A部分为本实施例一的：CS、PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS，SPEEK-CS@Mg的ATR-FTIR光谱图；B部分为本实施例一的：PEEK、SPEEK-H、SPEEK-NH2的光谱图，SPEEK-CS，SPEEK-CS@Mg的XPS光谱图；C部分：不同样品表面重要元素的高分辨率XPS光谱图。Part A of Fig. 2 is the ATR-FTIR spectrogram of CS, PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS, SPEEK-CS@Mg of the first embodiment; part B is the first embodiment of the present invention: PEEK , SPEEK-H, SPEEK-NH2 spectra, SPEEK-CS, SPEEK-CS@Mg XPS spectra; part C: high-resolution XPS spectra of important elements on different sample surfaces.

与SPEEK-CS的光谱相比，吸收峰在1648cm处-1和3394厘米-1移至1649厘米-1和3364厘米-1在SPEEK-CS@Mg的光谱中，这进一步说明Mg离子被成功地引入到SPEEK-CS产品的表面。Compared with the spectrum of SPEEK-CS, the absorption peaks at 1648 cm-1 and 3394 cm-1 shifted to 1649 cm-1 and 3364 cm-1 in the spectrum of SPEEK-CS@Mg, which further indicated that Mg ions were successfully Introduced to the surface of SPEEK-CS products.

将Mg离子引入SPEEK-CS后，SPEEK-CS@Mg的光谱显示Mg3d的特征峰在133.5eV和135.2eV处可分为两个明显的峰：Mg3d5/2和Mg3d3/2.这些结果证实了SPEEK-CS@Mg产品的成功构建。After introducing Mg ions into SPEEK-CS, the spectrum of SPEEK-CS@Mg shows that the characteristic peak of Mg3d can be divided into two distinct peaks at 133.5eV and 135.2eV: Mg3d5/2 and Mg3d3/2. These results confirm the SPEEK - Successful build of CS@Mg product.

此外一些实施例中的对照组：In addition, the control group in some embodiments:

PEEK和改良后的PEEK标本的SEM照片见图3的A部分。The SEM photographs of PEEK and modified PEEK specimens are shown in part A of Fig. 3.

与其他组相比，原始的PEEK表面光滑。PEEK磺化后，在SPEEK-H表面出现了一个三维(3D)多孔网络，孔径大约分布在0.5～5μm范围内。当用EDA修饰时，SPEEK-NH表面的孔径大小2.与SPEEK-HA表面相比，表明PEEK表面结构的变化是由于胺化过程中表层脱落或溶解。此外，SPEEK表面的微孔结构也在胺化过程中膨胀。此外，我们还观察到SPEEK-CS样品表面的孔径进一步减小，这与CS的覆盖范围有关。在与Mg离子进一步功能化后，SPEEK-CS@Mg的表面没有明显的改变，并保持了与SPEEK-CS相同的微观结构。SPEEK-CS@Mg的横截面表明，PEEK的表面改性对其体性能没有显著影响。但制备的目标样品(SPEEK-CS@Mg)显示出有利于细胞粘附和增殖的3D多孔微观结构。The pristine PEEK has a smooth surface compared to other groups. After sulfonation of PEEK, a three-dimensional (3D) porous network appeared on the surface of SPEEK-H, and the pore size was distributed in the range of 0.5-5 μm. When modified with EDA, the pore size of the SPEEK-NH surface was 2. compared with that of the SPEEK-HA surface, indicating that the change in the structure of the PEEK surface was due to exfoliation or dissolution of the surface during amination. In addition, the microporous structure of the SPEEK surface also expanded during the amination process. In addition, we also observed a further decrease in the pore size on the SPEEK-CS sample surface, which is related to the coverage of CS. After further functionalization with Mg ions, the surface of SPEEK-CS@Mg did not change significantly and maintained the same microstructure as SPEEK-CS. The cross-section of SPEEK-CS@Mg shows that the surface modification of PEEK has no significant effect on its bulk properties. But the prepared target sample (SPEEK-CS@Mg) showed a 3D porous microstructure favorable for cell adhesion and proliferation.

图3的(A)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的SEM照片；(B)部分为：SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的元素图。采用EDS法研究了PEEK和改性PEEK样品的元素组成和重要元素分布。图3中的A部分显示了不同样品的元素组成。纯PEEK样品的主要元素为碳和氧，SPEEK-H的EDS光谱中显示出1.78％的硫(S)元素。经EDA修饰后，SPEEK-NH2表面显示出8.17％的氮(N)元素，说明酰胺化反应已成功进行。结果表明，SPEEK-CS的C含量(75.23％)和N含量(6.24％)略低于SPEEK-NH2的C含量(78.28％和8.17％)，SPEEK-CS上的氧含量(17.59)高于SPEEK-NH2上的(分别为78.28％和8.17％)，这可能是由于硫酸软骨素分子中氧含量高所致。在SPEEK-CS@Mg表面，检测到0.66％的Mg元素，表明Mg离子已成功引入SPEEK-CS@Mg样品。另外，不同样品的重要元素分布如图3中的B部分所示。这些图谱表明，重要元素均匀分布在不同样品的表面。图4的(A)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的水接触角示意图，每组n＝为3；(B)部分为：PEEK、SPEEK-H、SPEEK-NH2、SPEEK-CS和SPEEK-CS@Mg的水接触角坐标图，每组n＝为3；(C)部分为：SPEEK-CS@Mg样品中1～15天的Mg离子的累积释放曲线。Part (A) of Figure 3 is: SEM photos of PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg; part (B) is: SPEEK-H, SPEEK-NH2, SPEEK-CS and Elemental diagram of SPEEK-CS@Mg. The element composition and important element distribution of PEEK and modified PEEK samples were studied by EDS method. Part A in Fig. 3 shows the elemental composition of different samples. The main elements of pure PEEK samples are carbon and oxygen, and the EDS spectrum of SPEEK-H shows 1.78% sulfur (S) element. After modified by EDA, the surface of SPEEK-NH2 showed 8.17% nitrogen (N) elements, indicating that the amidation reaction had been successfully carried out. The results show that the C content (75.23%) and N content (6.24%) of SPEEK-CS are slightly lower than that of SPEEK-NH2 (78.28% and 8.17%), and the oxygen content (17.59%) on SPEEK-CS is higher than that of SPEEK - on NH2 (78.28% and 8.17%, respectively), which may be due to the high oxygen content in the chondroitin sulfate molecule. On the SPEEK-CS@Mg surface, 0.66% Mg element was detected, indicating that Mg ions had been successfully introduced into the SPEEK-CS@Mg sample. In addition, the important element distributions of different samples are shown in part B of Fig. 3. These maps show that important elements are evenly distributed across the surfaces of the different samples. Part (A) of Figure 4 is: a schematic diagram of the water contact angle of PEEK, SPEEK-H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg, each group n=3; part (B) is: PEEK, SPEEK -H, SPEEK-NH2, SPEEK-CS and SPEEK-CS@Mg water contact angle coordinate diagram, each group n=3; part (C) is: Mg ions in SPEEK-CS@Mg samples from 1 to 15 days cumulative release curve.

图4中的A和B显示，镁离子的引入进一步降低了材料的接触角(约45°)，这与镁离子的亲水性有关。可见，CS和Mg离子的联合改性有效地改善了PEEK表面的亲水性。因此，SPEEK-CS@Mg的表面应该更适合细胞粘附和生长。图4C显示了SPEEK-CS@Mg样品中1～15天的Mg离子的累积释放曲线。其中，镁离子的释放行为显示，在最初的1天内，镁离子会快速释放。这是由于初始释放介质和材料之间的镁离子浓度差异较大，以及SPEEK中的镁离子-CS@Mg释放介质中的钠离子可以交换材料。然后，镁离子的释放速度显著减慢，培养基中Mg2+离子的含量在1至15天内达到稳定水平。这表明SPEEK-CS@Mg这种材料可以释放镁离子。镁离子不仅能诱导破骨细胞凋亡，还能促进成骨细胞增殖，这有利于刺激新骨形成。A and B in Figure 4 show that the introduction of magnesium ions further reduces the contact angle of the material (about 45°), which is related to the hydrophilicity of magnesium ions. It can be seen that the combined modification of CS and Mg ions effectively improves the hydrophilicity of the PEEK surface. Therefore, the surface of SPEEK-CS@Mg should be more suitable for cell adhesion and growth. Figure 4C shows the cumulative release curves of Mg ions in SPEEK-CS@Mg samples for 1–15 days. Among them, the release behavior of magnesium ions showed that in the first 1 day, magnesium ions would be released rapidly. This is due to the large difference in the concentration of magnesium ions between the initial release medium and the material, and the fact that magnesium ions in SPEEK-CS@Mg release medium can exchange materials for sodium ions. Then, the release rate of magnesium ions was significantly slowed down, and the content of Mg2+ ions in the medium reached a stable level within 1 to 15 days. This indicates that the SPEEK-CS@Mg material can release magnesium ions. Magnesium ions can not only induce osteoclast apoptosis, but also promote osteoblast proliferation, which is beneficial to stimulate new bone formation.

本发明方法用于骨科植入物时，形状要求不一，难于批量生产，也大多为小批量生产。因此，PEEK基材适合根据使用者的要求而制作，在制作完成之后，再进入上述步骤，进行表面改性。因此，还包括设于制成磺化PEEK步骤之前的预制步骤，根据接收到的需求3D图形生成模具，采用PEEK母粒进行模具成形，或者利用PEEK母材进行3D加工，制成PEEK基材。When the method of the present invention is used for orthopedic implants, the shape requirements are different, it is difficult to produce in batches, and most of them are produced in small batches. Therefore, the PEEK base material is suitable for making according to the user's requirements. After the production is completed, enter the above steps for surface modification. Therefore, it also includes a prefabrication step before the step of making sulfonated PEEK, generating a mold according to the received demand 3D graphics, using PEEK masterbatch for mold forming, or using PEEK base material for 3D processing to make a PEEK substrate.

如图5至图8所示的实施例，本发明还公开了一种用于PEEK种植体表面改性的设备，包括基座，设于基座上的若干个工位；还包括设于基座上的环形的导轨10，及与导轨10滑动联接的滑座20，用于驱动滑座20的驱动机构(即滑轨电机21；滑座20设有升降机构，以升降镂空治具30；需要加工的PEEK基材90置于镂空治具30内。The embodiment shown in Fig. 5 to Fig. 8, the present invention also discloses a kind of equipment that is used for PEEK implant surface modification, comprises base, is arranged on several stations on the base; Theannular guide rail 10 on the seat, and the slidingseat 20 that is slidingly connected with theguide rail 10, are used to drive the driving mechanism of the sliding seat 20 (i.e. theslide rail motor 21; the slidingseat 20 is provided with a lifting mechanism to lift thehollow fixture 30; ThePEEK substrate 90 to be processed is placed in thehollow jig 30 .

其中，工位包括丙酮清洗工位101、无水乙醇清洗工位102、去离子水清洗工位一103、第一恒温干燥工位104、硫酸超声波工位105、超纯水超声波工位106、超纯水水热工位107、乙二胺EDA工位108、去离子水清洗工位二109、异丙醇冲洗工位110、去离子水冲洗工位111、第二恒温干燥工位112、第一磁力搅拌工位113、第二磁力搅拌工位114、第三恒温干燥工位115。这些工位依次形成一个环形，在丙酮清洗工位101和第三恒温干燥工位115之间还设有一个上下料工位100。Among them, the stations includeacetone cleaning station 101, absoluteethanol cleaning station 102, deionized water cleaning station one 103, the first constanttemperature drying station 104, sulfuric acidultrasonic station 105, ultrapure waterultrasonic station 106, Ultrapure waterhydrothermal station 107,ethylenediamine EDA station 108, deionized water cleaning station 2 109,isopropanol rinsing station 110, deionizedwater rinsing station 111, second constanttemperature drying station 112, The first magnetic stirringstation 113 , the second magnetic stirringstation 114 , and the third constanttemperature drying station 115 . These stations form a ring in turn, and a loading and unloadingstation 100 is also provided between theacetone cleaning station 101 and the third constanttemperature drying station 115 .

升降机构的下端设有磁性联接座31，及设于磁性联接座31的联接孔311；镂空治具30的上端设有导磁件301，以磁性联接于联接孔311。The lower end of the lifting mechanism is provided with amagnetic connection seat 31 and aconnection hole 311 located in themagnetic connection seat 31 ;

本实施例中，升降机构为电缸32，还包括设于电缸32与磁性联接座31之间的超声波发生器33。In this embodiment, the lifting mechanism is anelectric cylinder 32 and also includes anultrasonic generator 33 disposed between theelectric cylinder 32 and themagnetic coupling seat 31 .

镂空治具30设有平形或球形的底部309，以及开口斜向上的入料口308；镂空治具30表面设有聚四氟乙烯涂层，可以采用高强度塑料或不锈钢当作基材。镂空治具30设有上挡板307，用于与各个工位的上开口形成密封联接；上挡板307的外侧面设有斜向下的导向斜面306，以快速与各个工位的上开口形成密封联接。The hollowed outjig 30 is provided with a flat orspherical bottom 309 and afeed inlet 308 with an upward opening; the surface of the hollowed outjig 30 is coated with polytetrafluoroethylene, and high-strength plastic or stainless steel can be used as the base material.Hollow fixture 30 is provided withupper baffle plate 307, is used for forming sealing connection with the upper opening of each station; Form a sealed joint.

更具体地，由于超纯水水热工位、乙二胺EDA工位、第一磁力搅拌工位、第二磁力搅拌工位的时间较长，因此，这四个工位，分别增加了转盘结构，分别为水热转盘51(有六个工位)、乙二胺转盘52(有五个工位)、第一磁力转盘53(有十个工位)、第二磁力转盘54(有六个工位)，转盘上面的有一个工位，与滑轨的工位重合；该重合工位用于放入或取出PEEK基材或PEEK中间体。因为在第一磁力搅拌工位、第二磁力搅拌工位之后均需要去离子清洗，为了进一步优化设备的空间，在第一磁力转盘53、第二磁力转盘54的多个工位中，分别设定一个工位为去离子水洗涤工位(也可以叫做去离子水冲洗工位)。第二恒温干燥工位112和第三恒温干燥工位115的时间也较长，可以采用二个水平移动的工位进行轮换，以保证与其它工位同样的效率。More specifically, since the ultrapure water hydrothermal station, ethylenediamine EDA station, the first magnetic stirring station, and the second magnetic stirring station take a long time, these four stations respectively increase the turntable The structure is respectively hydrothermal turntable 51 (with six stations), ethylenediamine turntable 52 (with five stations), the first magnetic turntable 53 (with ten stations), and the second magnetic turntable 54 (with six stations). There is a station above the turntable, which coincides with the station of the slide rail; this overlapping station is used to put in or take out the PEEK substrate or PEEK intermediate. Because deionization cleaning is required after the first magnetic stirring station and the second magnetic stirring station, in order to further optimize the space of the equipment, in the multiple stations of the firstmagnetic turntable 53 and the secondmagnetic turntable 54, respectively set Set a station as a deionized water washing station (also called a deionized water rinse station). The time of the second constanttemperature drying station 112 and the third constanttemperature drying station 115 is also longer, and two horizontally moving stations can be used for rotation to ensure the same efficiency as other stations.

总体上，这样的设备，能提高PEEK基材表面改性的效率，购买此类设备的生产商在获得产品认证之后，可以同时接受各地骨科医生的手术需要，及时交付合格产品，以供骨科手术等场合的使用。In general, such equipment can improve the efficiency of surface modification of PEEK substrates. After obtaining product certification, manufacturers who purchase such equipment can simultaneously accept the surgical needs of orthopedic surgeons in various places and deliver qualified products in time for orthopedic surgery. Use on other occasions.

还进一步地，包括控制器80，在滑轨的每个工位上方设有相对应的工位到达传感器81，到达该工位时，控制器80收到信号，停止滑轨电机的工作，将镂空治具停留在该工位的上方。还设有与控制器80联接的工位待机传感器82，该工位待机传感器82可以是接近开关、位置传感器或红外探测器，或者是该工位的设备的输出信号，以证明该工位的设备已经准备就绪。Still further, including acontroller 80, a correspondingstation arrival sensor 81 is provided above each station of the slide rail. When the station is reached, thecontroller 80 receives a signal, stops the work of the slide rail motor, and Hollow jig stays above the station. Also be provided with thestation standby sensor 82 that is connected withcontroller 80, thisstation standby sensor 82 can be proximity switch, position sensor or infrared detector, or the output signal of the equipment of this station, to prove the position of this station The equipment is ready.

其中，需要加热恒温的工位，设有上开口的加热腔，在上开口的位置不需要腔门，因为镂空治具30设有上挡板307就可以起到腔门的工作，只要上开口的边缘设有斜向上的导向斜面。Among them, the station that needs to be heated and kept at a constant temperature is provided with a heating chamber with an upper opening. There is no need for a chamber door at the position of the upper opening, because thehollow fixture 30 is provided with anupper baffle plate 307 and the work of the chamber door can be played. As long as the upper opening The edge is provided with an inclined upward guiding slope.

其中，有些工位带有挥发性物质，比如硫酸超声波工位，第二磁力搅拌工位、丙酮清洗工位这些工位，在未工作时，需要关闭其自身在上开口设有的腔门。Wherein, some stations have volatile substances, such as sulfuric acid ultrasonic station, these stations of the second magnetic stirring station, acetone cleaning station, when not working, need to close the chamber door that itself is provided with on the upper opening.

在进行PEEK种植体表面改性加工的过程中，先是加工出PEEK基材，再将PEEK基材装入镂空治具中，并于上下料工位，将磁吸于滑座下方，依次按步骤送至各个工位进行处理。时间较长的工位则是放于工位，且释放磁性吸力。回到上下料工位，再进行其它PEEK基材的加工。In the process of modifying the surface of PEEK implants, the PEEK base material is processed first, and then the PEEK base material is loaded into the hollowed out jig, and at the loading and unloading station, the magnetic attraction is placed under the sliding seat, and the steps are followed in turn. Sent to each station for processing. The station with a longer time is placed in the station and the magnetic attraction is released. Return to the loading and unloading station, and then process other PEEK substrates.

这些工位的具体结构可以采用以下的结构：The specific structure of these stations can adopt the following structure:

丙酮清洗工位101、无水乙醇清洗工位102、去离子水清洗工位一103、去离子水清洗工位二109、异丙醇冲洗工位110、去离子水冲洗工位111，均采用上开口的容器，利用输液泵将清洗用的液体连续不断地喷在PEEK工件上面；Acetone cleaning station 101, absoluteethanol cleaning station 102, deionized water cleaning station one 103, deionized water cleaning station two 109,isopropanol washing station 110, deionizedwater washing station 111, all using The upper opening of the container, using the infusion pump to continuously spray the cleaning liquid on the PEEK workpiece;

第一恒温干燥工位104、第二恒温干燥工位112、三恒温干燥工位115设有干燥腔体，且设有隔热效果良好的腔壁；The first constanttemperature drying station 104, the second constanttemperature drying station 112, and the third constanttemperature drying station 115 are provided with drying chambers and chamber walls with good heat insulation effect;

硫酸超声波工位105、超纯水超声波工位106、超纯水水热工位107，采用可以静置液体的工作腔；Sulfuric acidultrasonic station 105, ultrapure waterultrasonic station 106, ultrapure waterhydrothermal station 107, using a working chamber that can stand liquid;

乙二胺EDA工位108采用有回流冷凝模式的容器；Theethylenediamine EDA station 108 adopts a container with a reflux condensation mode;

第一磁力搅拌工位113、第二磁力搅拌工位114采用磁力搅拌器，工作时，镂空治具需离磁力棒至少10mm以上。The first magnetic stirringstation 113 and the second magnetic stirringstation 114 use a magnetic stirrer. When working, the hollow jig needs to be at least 10mm away from the magnetic bar.

改性加工过程中，在将PEEK基材从工位的液体中取出时，防止将强酸或强碱的液体带出工位之外，升降电缸在将镂空治具提升之后，在最高位置时，上下往复移动3-20次，频率为1-5次/秒，时长5-20秒，以将镂空治具和PEEK基材上面的残余液体初步脱离。During the modification process, when taking the PEEK base material out of the liquid in the station, prevent the strong acid or alkali liquid from being taken out of the station. , reciprocate 3-20 times up and down, the frequency is 1-5 times per second, and the duration is 5-20 seconds, so as to initially separate the residual liquid on the hollow fixture and the PEEK substrate.

为了节省电磁铁的功耗，磁性联接座31可以采用永磁铁，产生吸力，在需要释放时，电磁铁311则通电产生一个反向磁场，抵消永磁铁的磁场。In order to save the power consumption of the electromagnet, themagnetic coupling seat 31 can adopt a permanent magnet to generate an attractive force. When it needs to be released, theelectromagnet 311 is energized to generate a reverse magnetic field to offset the magnetic field of the permanent magnet.

在超纯水超声波工位106、超纯水水热工位107等时间较长的工位，由滑座与镂空治具分离，镂空治具不带超声波发生器时，这些工位本身需要带有超声波发生器。In the ultrapure waterultrasonic station 106, ultrapure waterhydrothermal station 107 and other stations with a long time, the sliding seat is separated from the hollowed out jig. When the hollowed out jig does not have an ultrasonic generator, these stations themselves need to carry There is an ultrasonic generator.

于其它实施例中，也可以将超声波发生器设在工位的设备的支撑台面，以提高效率。In other embodiments, the ultrasonic generator can also be arranged on the support table of the equipment in the work station to improve efficiency.

于其它实施例中，为了提高效率，可以多设几个滑座；镂空治具的数量则可以有很多个，因为时间较长的工位，需要放很多个在其工位。In other embodiments, in order to improve the efficiency, several more slide seats can be provided; the number of hollow jigs can be many, because the work stations with a long time need to put many at the work stations.

于其它实施例中，在镂空治具的底部设有由小变大的螺旋状通槽(顺时针或逆时针)。当在磁力搅拌工位时，磁力搅拌的方向也与螺旋状通槽的方向相同(顺时针或逆时针)，这样的结构，最大程度地减少镂空治具对磁力搅拌的干扰，以保证更好的磁力搅拌效果。进一步地，镂空治具的底部为圆盘状，且中心位置向上凸起，使得PEEK基材放入治具内里，会尽量分布于四周的位置，这样的结构，使得镂空治具在磁力搅拌工位时，PEEK基材远离旋转中心，处于流速较高的区域，能获得更好的搅拌效果。In other embodiments, a spiral channel (clockwise or counterclockwise) is provided at the bottom of the hollow jig. When in the magnetic stirring station, the direction of the magnetic stirring is also the same as the direction of the helical channel (clockwise or counterclockwise). This structure minimizes the interference of the hollow fixture on the magnetic stirring to ensure better magnetic stirring effect. Furthermore, the bottom of the hollowed out jig is disc-shaped, and the central position is raised upwards, so that the PEEK substrate is placed in the jig and will be distributed as far as possible around the position. When in position, the PEEK base material is far away from the rotation center, and is in the area of higher flow velocity, which can obtain better stirring effect.

本发明还公开了一种可以用于容纳PEEK基材、也可以用于其它液体磁力搅拌的镂空治具，镂空治具包括带有内空腔的镂空部，设于镂空部上方的联接部。进一步地，在镂空治具的底部设有由小变大的螺旋状通槽(顺时针或逆时针)。当在磁力搅拌时，磁力搅拌的方向也与螺旋状通槽的方向相同(顺时针或逆时针)，这样的结构，最大程度地减少镂空治具对磁力搅拌的干扰，以保证更好的磁力搅拌效果。进一步地，镂空治具的底部为圆盘状，且中心位置向上凸起，使得PEEK基材放入治具内里，会尽量分布于四周的位置，这样的结构，使得镂空治具在磁力搅拌工位时，PEEK基材之类的工件会远离旋转中心，处于流速较高的区域，能获得更好的搅拌效果。The invention also discloses a hollowed-out jig which can be used for accommodating PEEK substrates and magnetic stirring for other liquids. The hollowed-out jig includes a hollowed out part with an inner cavity and a coupling part arranged above the hollowed out part. Further, a spiral channel (clockwise or counterclockwise) is provided at the bottom of the hollow jig. When magnetic stirring is in progress, the direction of magnetic stirring is also the same as that of the helical channel (clockwise or counterclockwise). This structure minimizes the interference of the hollow fixture on magnetic stirring to ensure better magnetic force. stirring effect. Furthermore, the bottom of the hollowed out jig is disc-shaped, and the central position is raised upwards, so that the PEEK substrate is placed in the jig and will be distributed as far as possible around the position. When in position, workpieces such as PEEK substrates will be far away from the center of rotation, and will be in the area of higher flow rate, which can obtain better stirring effect.

综上所述，本发明PEEK种植体表面改性方法基于PEEK与乙二胺(EDA)的席夫碱反应和EDA与CS的酰胺化反应，首次将硫酸软骨素镁引入磺化PEEK(SPEEK-CS@Mg)表面。SPEEK-CS@Mg植入体表面具有三维微孔结构和良好的亲水性，并能释放镁离子。体外细胞实验表明SPEEK-CS@Mg具有良好的生物相容性和安全性。而且，与原来的PEEK相比，SPEEK-CS@Mg能显著促进细胞黏附和扩散，提高成骨活性和血管生成活性，减轻炎症反应。动物实验进一步证实SPEEK-CS@Mg有利于PEEK材料的成骨和成骨固定。因此，我们通过一种经济、简单、可重复、可行的方法，利用硫酸软骨素镁对PEEK材料进行表面改性，实现了良好的预期，将拓宽PEEK材料在骨科植入物中的应用。本发明设备则通过与导轨滑动联接的滑座，将PEEK基材放在滑座下方的镂空治具内，实现在不同工位之间移动，实现自动化的操作，减少人员操作的成本和失误。因为本发明的产品尺寸较小，一般用于骨科植入物，且因为使用的形状不一，属于单件小批量生产。因此，各个工位的设备，可以由实验室设备组合而成，经过必要的动力机构的组合即可实现，这样的结构成本低，易操作，且易维护。In summary, the PEEK implant surface modification method of the present invention is based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and CS. For the first time, magnesium chondroitin sulfate is introduced into sulfonated PEEK (SPEEK- CS@Mg) surface. The surface of SPEEK-CS@Mg implant has a three-dimensional microporous structure and good hydrophilicity, and can release magnesium ions. In vitro cell experiments showed that SPEEK-CS@Mg has good biocompatibility and safety. Moreover, compared with the original PEEK, SPEEK-CS@Mg can significantly promote cell adhesion and spreading, enhance osteogenic activity and angiogenic activity, and reduce inflammatory response. Animal experiments further confirmed that SPEEK-CS@Mg is beneficial to the osteogenesis and osteogenic fixation of PEEK materials. Therefore, our surface modification of PEEK material with magnesium chondroitin sulfate through an economical, simple, reproducible, and feasible method has achieved good expectations and will broaden the application of PEEK material in orthopedic implants. The equipment of the present invention puts the PEEK base material in the hollow jig under the sliding seat through the sliding seat slidingly connected with the guide rail, so as to realize the movement between different stations, realize the automatic operation, and reduce the cost and error of personnel operation. Because the size of the product of the present invention is small, it is generally used for orthopedic implants, and because the shapes used are different, it belongs to single-piece small-batch production. Therefore, the equipment of each station can be combined by laboratory equipment, and can be realized through the combination of necessary power mechanisms. Such a structure is low in cost, easy to operate, and easy to maintain.

上述仅以实施例来进一步说明本发明的技术内容，以便于读者更容易理解，但不代表本发明的实施方式仅限于此，任何依本发明所做的技术延伸或再创造，均受本发明的保护。本发明的保护范围以权利要求书为准。The above only uses examples to further illustrate the technical content of the present invention, so that readers can understand more easily, but it does not mean that the implementation of the present invention is limited to this, and any technical extension or re-creation done according to the present invention is subject to the present invention. protection of. The protection scope of the present invention shall be determined by the claims.

Claims (10)

1. A PEEK implant surface modification method is characterized by comprising the following steps:

(a) Providing a PEEK substrate;

(b) Dipping a PEEK base material in a concentrated sulfuric acid solution, and removing a solvent of the concentrated sulfuric acid solution to obtain a sulfonated PEEK material;

(c) Carrying out hydrothermal treatment reaction on the sulfonated PEEK material to obtain a SPEEK-H material;

(d) Putting the SPEEK-H material into a container filled with Ethylenediamine (EDA) for reaction to obtain a SPEEK-NH2 material;

(e) Adding the SPEEK-NH2 material into a prepared solution containing chondroitin sulfate, mixing, and removing the solvent of the prepared solution containing chondroitin sulfate to obtain the SPEEK-CS material;

(f) And (3) soaking the SPEEK-CS material in a magnesium hydroxide solution, removing a solvent of the magnesium hydroxide solution, washing and drying to obtain the SPEEK-CS @ Mg material.

2. The PEEK implant surface modification method according to claim 1, wherein in the step (b), the concentrated sulfuric acid solution has a concentration of more than 90% and a reaction temperature of 23-28 ℃.

3. The PEEK implant surface modification method according to claim 1, wherein, in the step (c), the hydrothermal treatment reaction includes immersing the sulfonated PEEK material in ultrapure water for 8-15h at a reaction temperature of 85-95 ℃.

4. The method for modifying the surface of a PEEK implant according to claim 1, wherein the reaction temperature is 120-135 ℃ in the step (d), and the process is continued for 3-5 hours after cooling.

5. The method for modifying a PEEK implant surface according to claim 1, wherein, in the step (e), the chondroitin sulfate-containing pre-preparation solution further includes a buffer and a coupling agent.

6. The PEEK implant surface modification method of claim 5, characterized in that the buffer, preferably morpholine ethanesulfonic acid, and the coupling agent, preferably EDC and NHS, are used.

7. An orthopedic implant, characterized in that the SPEEK-CS @ Mg material is processed by the PEEK implant surface modification method of claim 1.

8. The equipment for the PEEK implant surface modification method of claim 1, comprising a base and a plurality of stations arranged on the base, wherein the base is provided with a guide rail, the guide rail is connected with a sliding seat in a sliding manner, the bottom of the sliding seat is provided with a driving device for driving the sliding seat to slide, and an elevating mechanism, the bottom of the elevating mechanism is provided with a hollow jig, and the PEEK substrate to be processed is arranged in the hollow jig.

9. The equipment for PEEK planting surface modification according to claim 8, wherein the stations comprise an acetone cleaning station, an absolute ethyl alcohol cleaning station, a deionized water cleaning station I, a first constant temperature drying station, a sulfuric acid ultrasonic station, an ultrapure water hydrothermal station, an Ethylenediamine (EDA) station, a deionized water cleaning station II, an isopropanol washing station, a deionized water washing station, a second constant temperature drying station, a first magnetic stirring station, a second magnetic stirring station and a third constant temperature drying station.

10. The apparatus according to claim 8, wherein the lower end of the lifting mechanism is provided with a magnetic coupling seat and a coupling hole arranged on the magnetic coupling seat; the upper end of the hollow jig is provided with a magnetic conduction piece which is magnetically connected with the connecting hole, and the hollow jig is provided with an upper baffle plate which is used for forming sealing connection with the upper opening of each station; and the outer side surface of the upper baffle is provided with an inclined downward guide inclined surface so as to be quickly connected with the upper opening of each station in a sealing manner.

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