冠脉支架表面载药涂层的制备和性能

采用溶液聚合法制备了改性的聚甲基丙烯酸树脂,作为支架表面载药涂层的药物载体聚合物.采用浸涂法制备了不锈钢基体表面聚合物及聚合物载药涂层,并利用红外光谱及核磁共振波谱分析了所制备共聚物的成分,并评价了物理性能、生物稳定性能以及药物的释放性能.结果表明,所制备的涂层具有较好的生物稳定性,甲基丙烯酸和甲基丙烯酸丁酯的加入提高了聚合物的物理性能,尤其是涂层与金属基体的结合力所制备的药物释放涂层具有缓释紫杉醇的功能,其释放周期超过15 d.聚甲基丙烯酸树脂携带紫杉醇的载药涂层在生物稳定性、物理性能及药物释放性能方面满足冠脉支架的表面涂层的使用要求.     

水分散聚己内酯载雷帕霉素纳米微球包封率的HPLC测试

随着支架的应用越来越广泛,支架表面的药物涂层开始受到人们的重视。文章首先制备了水分散聚己内酯载雷帕霉素纳米微球载药涂层液,然后通过高速离心和甲醇萃取方法提纯纳米微球内的雷帕霉素,采用高效液相色谱仪测试载药纳米微球的包封率,得到提纯载药纳米微球中雷帕霉素的方法和雷帕霉素的最佳萃取时间,确定雷帕霉素在5．0～50μg／mL的浓度范围内具有良好的线性,以及高效液相色谱仪测试雷帕霉素的测定条件。     

冠脉支架表面PLGA涂层制备及其血液相容性研究

采用静电喷涂沉积(electrospray deposition ESD)法在冠脉支架表面制备了PLGA涂层.采用OLYMPUS体式显微镜、原子力显微镜(AFM)观察了涂层宏观表面形貌及三维形貌;通过对涂层支架进行球囊扩张考察了PLGA涂层与支架的结合力;通过血小板粘附实验和动态凝血时间测定研究PLGA涂层的血液相容性.结果表明:ESD法在冠脉支架表面制备PLGA涂层,支架筋拐角处无明显的聚合物胶体缠绕、粘连且涂层表面光滑;PLGA涂层将316L不锈钢基体的微坑覆盖,基体Ra=16.174nm,PLGA涂层Ra=0.149nm,涂层表面粗糙度小;涂层支架撑开后在最大塑性变形位置无涂层撕裂、翘起等缺陷,涂层与支架有良好结合力;PLGA涂层血小板粘附量少,变形小,未引起血小板激活,动态凝血时间长,直到50min未产生凝血,PLGA涂层具有较好的血液相容性.     

冠脉支架表面聚醚聚氨酯涂层的制备工艺及性能研究

利用浸涂方法在不锈钢冠脉支架表面制备出聚醚聚氨酯涂层.针对冠脉支架复杂的网状结构,对制备工艺进行了研究.结果表明,该涂层具有完整无缺陷的表面形貌,低的表面粗糙度,满足要求的力学性能,并保持了聚醚聚氨酯的微相分离结构,从而保证了良好的血液相容性.本项研究为探索简便而有效的支架表面涂层制备工艺奠定了基础.     

生物医用微孔高分子涂层的制备及其初始降解形貌的研究

主要研究了316L不锈钢基体表面微孔聚丙交酯/乙交酯(PLGA)高分子载药涂层的制备技术,探索出空气湿度、温度、涂膜液的浓度等参数对涂层表面的孔径影响的规律,制备出孔径均匀的不锈钢表面PLGA涂层,并对微孔涂层在人工模拟体液(hank's溶液)中的初始降解(3个星期)形貌进行了考察,从而为开发心血管介入治疗不锈钢支架上的微孔载药涂层技术奠定基础.     

生物医用镁合金耐腐蚀性能研究进展

生物医用镁合金具有高比强度、低密度、合适的弹性模量、可降解性、良好的生物相容性及生物力学相容性等优点,在骨科固定和心血管支架等领域具有广泛的临床应用前景.然而,由于镁合金腐蚀过快和不均匀腐蚀等问题,易导致其过早丧失力学完整性,从而限制了其在承重部位的临床应用.本文从镁合金腐蚀类型、影响腐蚀性能的自身因素及外部因素、提高镁合金自身耐蚀性能及表面改性等方面系统综述了近年来的研究进展,并对生物镁合金耐蚀性能研究的未来发展趋势进行了展望:一方面,通过低合金化、高纯化及细晶化等手段改善镁合金自身耐腐蚀性能;另一方面,从耐蚀、抗菌及载药等方面着手设计可靠涂层;此外,研究镁合金植入器械的腐蚀降解行为及机理还需综合考虑腐蚀介质流场应力等体内服役因素.     

超声雾化喷涂法制备抗血小板膜糖蛋白单克隆抗体洗脱支架及其生物相容性研究

采用超声雾化喷涂法制备抗血小板膜糖蛋白单克隆抗体洗脱支架。以涂层均匀度和接触角大小来优化壳聚糖单抗涂层参数,在外层喷涂一层左旋聚乳酸作为屏蔽层控制单抗SZ-21的释放速度。通过溶血率检测涂层支架的血液相容性;MTT实验和细胞粘附实验考察涂层支架的细胞相容性。对支架表面涂层进行SEM和EDS分析,结果表明,聚合物和单抗成功涂层到支架表面,且涂层均匀。涂层支架溶血率低于国家标准的5%,涂层支架对血管内皮细胞没有产生明显的毒副作用;涂层支架有良好的细胞相容性,利于细胞在支架上生长。具有屏蔽层的单抗SZ-21涂层支架较没有涂层屏蔽层的单抗SZ-21涂层支架的SZ-21释放明显成缓慢释放,无暴释现象。     

羟基磷灰石/聚醚酯聚氨酯支架的体外降解行为和细胞相容性研究

采用XRD、DSC、体外降解实验和细胞相容性实验等方法对羟基磷灰石/聚醚酯聚氨酯(HA/PU)多孔支架的结构和性能进行了研究。结果表明,HA粒子添加到聚醚酯聚氨酯基体中,在一定程度上降低了聚氨酯软段的结晶,提高了聚氨酯基体的力学性能。体外降解实验表明HA/PU复合支架的降解不会引起浸泡液pH值较大的波动,且降解初期的力学性能衰减缓慢。MG63细胞与HA/PU复合支架共培养的实验表明,细胞生长良好,牢固地黏附在支架表面,并在支架表面充分伸展,复合支架具有良好的细胞相容性。这些结果表明HA/PU支架有望用于骨组织工程修复。     

PLGA携载紫杉醇涂层包被TiNi合金的表面特性与生物性能

系统研究了PLGA携载紫杉醇包被TiNi合金的表面特性与生物性能。采用原子力显微镜(AFM)和X射线光电子能谱(XPS)研究了药物涂层的表面形貌及化学成分;采用高效液相色谱(HPLC)研究了在pH为7.4的PBS溶液中紫杉醇从TiNi合金表面涂层中释放特性,并通过血小板粘附试验研究了药物涂层的血液相容性。试验结果表明经涂覆后TiNi合金表面化学组成及结构随着载药量的增加而改变。紫杉醇在涂层降解初期释放较快,随着时间的延长,累积释放量增加缓慢。血小板粘附试验表明载药量为0%、10%、20%和30%时涂膜样品表面血小板粘附数量均小于未涂膜样品表面。而随着载药量的增加,涂膜样品表面粘附的血小板数量增加,血小板变形严重,当载药量为30%时,血小板出现明显的聚集现象。     

聚丙交酯-乙交酯聚合物(PLGA)涂层体外降解行为研究

为了防止心血管支架植入后再狭窄的发生,目前采用将抑制平滑肌细胞生长的药物通过高分子载体涂在支架表面.由于支架植入体内后,涂层受到血液冲刷作用.本工作采用可降解高分子材料PLGA作为载体,将PLGA薄膜置于体外循环冲刷装置中,在37℃、pH7.4的Hank's模拟体液、模拟血流冲刷作用下的体外降解,并与静态降解作为对比.采用SEM、GPC、1H-NMR和DSC技术研究了聚合物在降解过程中形貌、分子量及分子量分布、失重率、组成和热性能的变化,并对降解机理进行探讨.与静态降解相比较,在流动体液中,高分子载体表面形貌、失重率以及分子量变化均较慢.上述结果与表面微环境有关.     

Inorganic materials as drug delivery systems in coronary artery stenting

Recent studies proved coronary stent implantation to be superior over conventional angioplasty in the treatment of coronary artery disease. However, restenosis remains one of the most crucial problems in interventional cardiology. Inflammatory infiltrates and foreign body reactions can be found in the tissue surrounding the struts in stenting. Thrombogenesis, proliferation of α‐actin expressing cells (smooth muscle cells) and hyperplasia of the intima occur. In order to improve the biocompatibility of the stents, new stent designs and stent coatings have been developed. One advantage of stent coating is the combination of mechanical stability of the stent with the biocompatibility of the coating. The coatings are divided into active and passive coatings. Passive coatings improve the biocompatibility of the stent, while active coatings may suppress neointima proliferation by releasing anti‐inflammatory or antiproliferative substances. Immunosuppressive drugs (tacrolimus, sirolimus) and cytostatic drugs (paclitaxel) have been tested in several studies and showed promising results. However, it could also be demonstrated that polymer‐coated stents used as a matrix for drug release reduced the hyperplasia of the intima. However, after dissipation of the immunosuppressants or cytostatics, the presence of the polymer itself lead to a delayed inflammation and proliferation causing restenosis. Thus, efforts have been made to develop inorganic coatings that are suitable for drug loading. One promising approach is a new nanoporous alumina coating. Preliminary tests with this coating revealed favourable loading characteristics and sustained drug release in vivo. The present article provides an overview on different approaches for stent coatings.     

Electrocoating of stainless steel coronary stents for extended release of Paclitaxel

The purpose of this study was to examine chemical, mechanical and Paclitaxel release properties of the new coating onto the stainless steel coronary stents.MethodsStainless steel coronary stents were coated with electrically polymerizable pyrrole derivative, applying cyclic voltammetry technique in a simple three electrode cell, while stent represented a working electrode. Resulted polymer coating were examined by cyclic voltammetry (electrical parameters), SEM (morphology images), goniometer (hydrophobisity of the surface), prophilometer ( thickness of the polymer coating). Polymer stability was examined by placing the coated stent into 1:1 solution of fetal calf serum:seline solution up to 1 year and under the mouse skin for 1 week. Paclitaxel loading were carried out by immersion into drug solution and its release was detected by HPLC.Results and conclusionReproducible one step method for coating different pyrrole derivatives on stainless steel coronary stents provided thin (single micrometers), uniform coating with various morphology and hydrophobisity. These surface properties allow to load appropriate amount of Paclitaxel and to release it slowly up to a month.     

Blood compatibility of zinc–calcium phosphate conversion coating on Mg–1.33Li–0.6Ca alloy

Magnesium alloys as a new class of biomaterials possess biodegradability and biocompatibility in comparison with currently used metal implants. However, their rapid corrosion rates are necessary to be manipulated by appropriate coatings. In this paper, a new attempt was used to develop a zinc-calcium phosphate (Zn-Ca-P) conversion coating on Mg-1.33Li-0.6Ca alloys to increase the biocompatibility and improve the corrosion resistance. In vitro blood biocompatibility of the alloy with and without the Zn-Ca-P coating was investigated to determine its suitability as a degradable medical biomaterial. Blood biocompatibility was assessed from the hemolysis test, the dynamic cruor time test, blood cell count and SEM observation of the platelet adhesion to membrane surface. The results showed that the Zn-Ca-P coating on Mg-1.33Li-0.6Ca alloys had good blood compatibility, which is in accordance with the requirements for medical biomaterials.     

Phosphorylcholine-based polymer coatings for stent drug delivery

Phosphorylcholine-based polymers have been used commercially to improve the biocompatibility of coronary stents. In this study, one particular polymer is assessed for its suitability as a drug delivery vehicle. Membranes of the material are characterized in terms of water content and molecular weight cut-off, and the presence of hydrophilic and hydrophobic domains investigated by use of the hydrophobic probe pyrene. The in vitro loading and elution of a variety of drugs was assessed using stents coated with the polymer. The rate of a drug's release was shown not to be simply a function of its water solubility, but rather more closely related to the drug oil/water partition coefficient. This finding was explained in terms of the more hydrophobic drugs partitioning into, and interacting with, the hydrophobic domains of the polymer coating. The suitability of the coated stent as a drug delivery vehicle was assessed in vivo using a radiolabeled analog of one of the more rapidly eluting drugs, angiopeptin. Autoradiography showed that the drug was released locally to the wall of the stented artery, and could be detected up to 28 days after implantation.     

Corrosion and drug release properties of EN-plating/PLGA composite coating on MAO film

The electroless nickel plating/poly(dl-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder diffraction (XRD) were used to analyze the morphology and the composition of the EN-plating. The corrosion behavior of the magnesium alloy substrate and the status of the drug in the PLGA matrix were respectively evaluated by Potentiodynamic polarization and Differential scanning calorimetry (DSC). The drug release was determined by ultraviolet–visible (UV–visible) spectrophotometer. EN-plating coating which was composed of compact cauliflower nodules was uniform in size and defect free with no pores or cracks. EN-plating could seal the microcracks and microholes on the outer layer of the MAO coating effectively. The corrosion resistance was improved by preventing the corrosive ions from diffusing to the magnesium alloy substrate. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases.     

Estimation of the strength of adhesion between a thermoresponsive polymer coating and nitinol wire

As polymer coatings become more widely used in the biomedical device industry, both to improve biocompatibility and as coatings for localised drug delivery, quantitative methods to measure the adhesive strength between coatings and substrates become a very important consideration. The aim of this study was to take a method for estimating the interfacial fracture toughness of a film to a flat substrate and apply it to Nitinol wires used in the production of medical devices. An investigation into the affect of surface roughness on the fracture toughness was also conducted. For the present study, a thermoresponsive based Poly (N-isopropylacrylamide) polymer was coated onto nitinol wire substrates and the adhesion strength between the polymer and wire was measured using a nanoindentation technique. Different surface treated nitinol wires, with different surface topography and roughness were used, and the affect of these surface properties on adhesion strength was investigated. Results showed that it was possible to apply the delamination technique to wire samples and obtain fracture toughness values. Results also showed that the surface roughness is an important parameter that can affect the adhesion between a coating and the substrate. It was found that, as the average surface roughness increased so also did the adhesive strength between the coating and wire sample.     

Enhanced cell adhesion to silicone implant material through plasma surface modification

Silicone implant material is widely used in the field of plastic surgery. Despite its benefits the lack of biocompatibility this material still represents a major problem. Due to the surface characteristics of silicone, protein adsorption and cell adhesion on this polymeric material is rather low. The aim of this study was to create a stable collagen I surface coating on silicone implants via glow-discharge plasma treatment in order to enhance cell affinity and biocompatibility of the material. Non-plasma treated, collagen coated and conventional silicone samples (non-plasma treated, non-coated) served as controls. After plasma treatment the change of surface free energy was evaluated by drop-shape analysis. The quality of the collagen coating was analysed by electron microscopy and Time-Of-Flight Secondary Ion Mass Spectrometry. For biocompatibility tests mouse fibroblasts 3T3 were cultivated on the different silicone surfaces and stained with calcein-AM and propidium iodine to evaluate cell viability and adherence. Analysis of the different surfaces revealed a significant increase in surface free energy after plasma pre-treatment. As a consequence, collagen coating could only be achieved on the plasma activated silicone samples. The in vitro tests showed that the collagen coating led to a significant increase in cell adhesion and cell viability.     

三维钛网表面双生物陶瓷涂层的制备及其性能

采用浸渍涂敷-烧结法首次在医用三维钛网表面制备出双生物陶瓷涂层,利用X射线衍射、场发射扫描电子显微镜对HA-BG/BG/Ti复合材料进行了微观表征,拉伸法测量了Ti基体与BG涂层的结合强度,模拟人体体液(SBF)评价复合材料的生物相容性.研究表明:该双生物陶瓷涂层的内层为生物玻璃(BG)涂层,外层为多孔结构的羟基磷灰石-生物玻璃(HA-BG)复合涂层.Ti基体被致密的BG涂层包覆,由于在BG/Ti界面发生化学反应,界面的结合强度提高,平均结合强度达27 MPa.生物相容性实验表明,HA-BG/BG/Ti复合材料表面会被一层整齐、致密的HA覆盖,具有良好的生物相容性.     

Novel hydroxyapatite/tantalum surface coating for metallic dental implant

The aim of this study was to design and produce a novel surface composite coating on metallic substrate in order to improve the biocompatibility of metallic dental implant and the bone osteointegration simultaneously.Stainless steel 316L (SS) was used as a metallic substrate and a novel double-layer hydroxyapatite/tantalum (HA/Ta) coating was prepared on it. Tantalum coating was made using physical vapor deposition process and HA coating was produced using plasma-spraying technique on it. X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques were utilized to investigate the coating characterization. Electrochemical polarization tests were performed in two types of physiological solutions at 37 ± 1 °C in order to determine the corrosion behavior of the coated and uncoated specimens as indication of biocompatibility.The results indicated that the decrease in corrosion current density was significant for HA/Ta coated specimens and was much lower than the value obtained for uncoated 316L SS. The novel double-layer HA/Ta composite coating could improve the corrosion resistance and thus the biocompatibility of 316L SS dental implant.