Fe-Mn合金在生物医学方面的应用及前景

生物可降解支架是在植入手术后血管修复期间为血管提供一定的支撑作用,然后预期在血管修复完成后一段时间内,通过与体内环境的相互作用转化成无毒性的降解产物被人体所吸收或排出体外。因此,人们对作为可降解支架的金属材料的力学性能、耐腐蚀性、降解特性、生物相容性等都提出了严格的要求。近年来,铁基合金作为可降解金属材料成为生物医学领域新的研究热点。纯铁是人体必需的微量元素之一,且具有优异的力学特性、耐腐蚀性、降解特性、生物性能以及加工成型性,这使得铁基合金作为生物医用可降解材料成为可能。然而,纯铁的降解速率过慢,这是阻碍其作为生物医用金属材料的主要问题之一。合金化在改善铁基材料降解性能的同时也可以改善力学性能,从而提高铁基材料的综合性能。在提高降解速率的同时,铁基材料也应保证足够的力学性能来支撑血管,并且力学性能越好、支架壁越薄、质量越小,则越能缩短降解时间,降解产物越少,对人体的毒性也越小。本文综述了铁基合金作为支架材料的研究现状,以及目前报道的铁锰合金的力学性能、腐蚀降解性能以及体外细胞相容性,并重点介绍了铁锰合金在生物可降解支架方面的研究现状以及需解决的关键问题,同时给出可能的解决方案。     

可降解金属血管支架研究进展

随着心血管疾病治疗技术的发展,各种金属血管支架作为治疗心血管疾病的最有效器械之一,已经越来越受到人们的关注。重点介绍了目前研究最广泛的2类可降解金属血管支架材料:镁基合金和铁基合金。总结了这2类血管支架用可降解金属材料的研究进展,血管支架器械的动物试验和临床试验研究成果。归纳了可降解金属血管支架的有限元结构设计、应力分析、体内体外降解性能和生物相容性等需要重点考虑的属性。指出了可降解金属血管支架目前存在的不足,并对可降解金属血管支架未来的研究方向和发展前景进行了展望。     

生物医用可降解锌基合金的研究进展

锌基合金是近几年新兴的一种医用可降解材料,有望应用于心血管支架及骨植入等医疗器械。锌是人体必需的营养元素,具有良好的生物相容性及适宜的体内降解速率,作为可降解合金的基体有很广的应用前景。然而,生物可降解锌基合金的设计、加工、强化及降解机理等研究尚处于起步阶段,还需要做大量的基础研究工作。本文以最终医疗器械产品的理想标准要求为切入点,从生物相容性、力学性能及抗腐蚀性能等方面对近几年医用锌基合金的研究成果进行了综述分析,并展望了其未来的发展方向。     

可降解镁合金材料的研究新进展

可降解镁合金材料因力学性能佳、生物相容性好以及可降解吸收等特点在植入材料领域成为研究热点。综述了可降解镁合金材料作为心血管支架、骨固定材料和多孔修复材料等的最新研究进展,阐述了其在体内的降解机理以及通过高纯镁合金开发、合金化、表面处理和快速凝固工艺等方法提高镁合金材料耐体液腐蚀性能,指出了目前可降解镁合金材料研究需要解决的问题和未来研究方向,并展望了其今后的临床应用前景。     

可降解锌基合金在骨科领域的研究进展

进入21世纪以来,随着材料科学的进步,医用金属植入材料从传统的316L不锈钢、钛合金等惰性金属材料逐渐转向可降解金属材料。可降解金属材料由于其良好的生物相容性和适宜的降解速率,可以在完成植入任务时被人体吸收,无需二次手术将内植物取出,从而引起广泛关注。在过去的10多年里,镁和铁及其合金作为医用可降解金属被广泛研究。锌是人体所必需的营养元素之一,因具有良好的生物相容性和适宜的降解速率,锌基合金在最近几年里成为继镁基和铁基合金之后又一具有广泛应用前景的医用可降解金属。然而,对锌基合金的设计和制备等仍处于初步阶段,还有大量的研究工作需要完成。综述了生物降解锌近年来用于骨科领域的研究进展,重点讨论了锌及其合金的力学性能、生物降解性能和生物相容性以及锌的合金化和制造技术之间的关系。     

生物可降解锌基金属材料研究进展

随着人们医疗观念的转变和材料科学的进步,医用金属植入材料的选择从传统316L不锈钢、钴铬合金、钛合金等惰性金属逐渐转向可降解材料。为了减轻与耐腐蚀支架相关的副作用(即慢性炎症和晚期血栓形成),目前正在开发新一代的生物可吸收支架,支架在完成任务后会被逐渐降解和吸收。目前的可降解金属主要包括镁合金、铁合金和锌合金,铁在动脉中产生大量的氧化产物而镁及其合金又腐蚀得太快。其中,锌合金具有更适宜的降解速度、良好的降解行为和较好的力学性能,基于锌的生物可吸收材料是近年兴起的最具发展潜力的可降解医用金属材料。本文主要介绍了纯锌、锌铜系、锌镁系及其他锌基合金近年来的主要研究进展。     

可降解血管支架材料降解行为研究进展

目前可降解血管支架材料包括聚合物、镁合金、铁合金及锌合金,它们的降解特性直接影响其作为血管支架植入后的支撑能力、局部反应和血管修复的预后。聚合物降解时间较易调整、生物相容性较好,但力学性能不足;镁合金的降解存在降解速率快、释氢反应和微环境pH值变化较大的问题;铁合金降解速率太慢;锌合金的降解速率适中,是近年可降解血管内植入材料研究热点。除了材料自身的特性,可降解材料的血管内降解行为还受到环境的离子浓度、酶、pH值和温度等多种因素的影响。综述了目前不同血管内可降解支架材料在模拟体液及动物体内生物降解行为的研究结果,以期为血管内可降解材料研究和产品开发提供参考。     

可降解材料现状及其在海洋领域的研究进展

目的 综述可降解材料（光降解材料、生物降解材料和光-生物降解材料）的研究现状,探讨可降解材料在海洋领域的研究进展和未来研究方向。方法 综述各类可降解材料的特性、应用及其降解机理,并从材料降解机理的角度讨论可降解材料在海水中的降解可行性及相应的材料改性方法。结果 由于海水环境存在特殊性,各类可降解材料在海水中的降解性能大幅下降,降解过程受诸多因素影响,为了使材料能在海水环境下降解,针对降解材料改性研究方面提出了建议。结论 可降解材料虽是目前材料领域的研究热点,但可降解材料在海洋领域的应用仍处于起步阶段,因此,开发出具有良好水降解性能的可降解材料是解决海洋污染问题的重点,也是未来研究的难点和热点。     

我国淀粉基生物可降解材料的研究进展

淀粉具有来源广泛、易于再生等特点使得发展以淀粉基为主导的降解材料具有较大的可行性,伴随着国家、社会及家庭个人对生物降解材料理解的愈加充分,淀粉基可生物降解材料的研究应用领域越来越广泛。通过整理现有资料,论述了淀粉基生物可降解材料的发展历程、淀粉基生物可降解材料生产工艺的改进以及现阶段新型淀粉基生物可降解材料的研究开发及应用,并展望了未来的研究方向。     

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.     

Assessment of structure integrity,corrosion behavior and microstructure change of AZ31B stent in porcine coronary arteries

Magnesium alloy coronary stent becomes a hot research topic due to its biodegradable character for avoiding late thrombosis and late restenosis. However, fracture of Mg alloy stent was a common issue after implantation. In this study, 18 drug-eluting biodegradable AZ31 B stents were implanted into porcine coronary arteries to assess its structural integrity, corrosion behavior and microstructure change in vivo.The coronary artery tissue responses to AZ31 B stent implantation were detected by quantitative coronary angiography and optical coherence tomography at the set time periods. In addition, further analyses were focused on the stent structure integrity, corrosion behaviors and the microstructure change of Mg alloy stents after implantation. A large number of fractures on stent struts were observed by high-resolution transmission X-ray tomography clearly. Moreover, degradation products, twins and grain refinement that appeared in Mg alloy stent matrix after implantation were also observed during the study. Inferred from this study, it is shown that the loss of AZ31 B stent structural integrity may be the result of stress concentration, degradation and microstructure change.     

Modification of Iron with Degradable Silver Phases Processed via Laser Beam Melting for Implants with Adapted Degradation Rate

In medical technology, implants are used to improve the quality of patients’ lives. The development of materials with adapted properties can further increase the benefit of implants. If implants are only needed temporarily, biodegradable materials are beneficial. In this context, iron-based materials are promising due to their biocompatibility and mechanical properties, but the degradation rate needs to be accelerated. Apart from alloying, the creation of noble phases to cause anodic dissolution of the iron-based matrix is promising. Due to its high electrochemical potential, immiscibility with iron, biocompatibility, and antibacterial properties, silver is suited for the creation of such phases. A suitable technology for processing immiscible material combinations is powder-bed-based procedure like laser beam melting. This procedure offers short exposure times to high temperatures and therefore a limited time for diffusion of alloying elements. As the silver phases remain after the dissolution of the iron matrix, a modification is needed to ensure their degradability. Following this strategy, pure iron with 5 wt% of a degradable silver–calcium–lanthanum alloy is processed via laser beam melting. Investigation of the microstructure yields achievement of the intended microstructure and long-term degradation tests indicates an impact on the degradation, but no increased degradation rate.     

可降解镁合金表面载药涂层的制备和性能

在可降解AZ31B镁合金心血管支架表面成功制备了携带雷帕霉素的聚乳酸-聚三亚甲基碳酸酯(PLA-PTMC)共聚物涂层,评价了涂层的表面形貌、降解性能、血液相容性和药物释放性能.结果表明,PLA-PTMC共聚物作为载药涂层具有良好的柔韧性,表面均匀、光滑,降解周期超过1个月,血液相容性良好.涂层具有缓释雷帕霉素的功能,释药周期超过1个月,可在内膜增生期内有效抑制支架植入后再狭窄的发生,满足冠脉支架表面载药层的使用要求.     

可生物降解镁合金血管支架管坯的材料制备及成形研究进展

对可生物降解镁合金血管支架的研究现状进行了综述。镁合金作为新型可降解物材料成为了研究热点,其中血管支架是其最有前景的应用方向之一。镁合金微细管材成形困难及镁合金血管支架腐蚀速率过快,是制约其大规模临床应用的2个主要因素。作者介绍了近期国内外的相关研究,包括改善镁合金力学性能,以及为提高成形极限采取的新成形方法,为提高镁合金耐腐蚀性而采取的各种处理方法等。     

Anticorrosion and cytocompatibility behavior of MAO/PLLA modified magnesium alloy WE42

Recently, biodegradable magnesium alloys have been introduced in the field of cardiovascular stents to avoid the specific drawbacks of permanent metallic implants. However, the major obstacle of the clinical use of magnesium-based materials is their rapid corrosion rate. In this paper, a composite micro-arc oxidation/poly-l-lactic acid (MAO/PLLA) coating was fabricated on the surface of the magnesium alloy WE42 to improve its corrosion resistance and the cytocompatibility of the modified materials was also investigated for safety aim. In our study, the morphology of materials was analyzed by Scanning electron microscopy. Potentiodynamic polarization was used to evaluate the corrosion behavior of the samples and corrosion weight loss was used to demonstrate their degradation rate. Furthermore, we applied cytotoxicity test in testing the cytocompatibility of the modified samples. The results showed that the PLLA coating effectively sealed the microcracks and micropores on the surface of the MAO coating by physical interlocking to interfere the corrosion ions. The corrosion rate was decreased and the cyototoxicity test showed that the MAO/PLLA composite coating WE42 had good cytocompatibility.     

Addressing the slow corrosion rate of biodegradable Fe-Mn: Current approaches and future trends

The movement towards the commercialization of biodegradable Fe has been hampered by the perceived slow degradation rate of the metal in physiological environments. The introduction of Fe-Mn alloys offers promise due to its significantly improved biocorrosion rates, excellent biocompatibility, and non-magnetic properties. However, the issue of slow corrosion rates persists in this alloy and its future hinges on addressing this issue. This short review report presents the current approaches to address this problem, the challenges concerning Fe-Mn corrosion, and some future techniques that may improve the degradation rate of Fe-Mn alloys.     

Hierarchical microstructure and two-stage corrosion behavior of a high-performance near-eutectic Zn-Li alloy

In order to improve mechanical and corrosion properties of biodegradable pure Zn,a knowledge-based microstructure design is performed on Zn-Li alloy system composed of hard β-LiZn4 and soft Zn phases.Precipitation and multi-modal grain structure are designed to toughen β-LiZn4 while strengthen Zn,resulting in high strength and high ductility for both the phases.Needle-like secondary Zn precipi-tates form in β-LiZn4,while fine-scale networks of string-like β-LiZn4 precipitates form in Zn with a tri-modal grain structure.As a result,near-eutectic Zn-0.48Li alloy with an outstanding combination of high strength and high ductility has been fabricated through hot-warm rolling,a novel fabrication process to realize the microstructure design.The as-rolled alloy has yield strength (YS) of 246 MPa,the ultimate tensile strength (UTS) of 395 MPa and elongation to failure (EL) of 47 ％.Immersion test in simulated body fluid (SBF) for 30 days reveals that Li-rich products form preferentially at initial stage,followed by Zn-rich products with prolonged time.Aqueous insoluble Li2CO3 forms a protective passivation film on the alloy surface,which suppresses the average corrosion rate from 81.2 μm/year at day one down dramatically to 18.2 μm/year at day five.Afterwards,the average corrosion rate increases slightly with decrease of Li2CO3 content,which undulates around the clinical requirements on corrosion resistance(i.e.,20 μm/year) claimed for biodegradable metal stents.     

On the cytocompatibility of biodegradable Fe-based alloys

Biodegradable iron-based alloys are potential candidates for application as temporary implant material. This study summarizes the design strategy applied in the development of biodegradable Fe–Mn–C–Pd alloys and describes the key factors which make them suitable for medical applications. The study's in vitro cytotoxicity tests using human umbilical vein endothelial cells revealed acceptable cytocompatibility based on the alloys' eluates. An analysis of the eluates revealed that Fe is predominantly bound in insoluble degradation products, whereas a considerable amount of Mn is in solution. The investigation's results are discussed using dose–response curves for the main alloying elements Fe and Mn. They show that it is mainly Mn which limits the cytocompatibility of the alloys. The study also supplies a summary of the alloying elements' influence on metabolic processes.The results and discussion presented are considered important and instructive for future alloy development. The Fe-based alloys developed show an advantageous combination of microstructural, mechanical and biological properties, which makes them interesting as degradable implant material.     

Biocompatibility of pure iron: In vitro assessment of degradation kinetics and cytotoxicity on endothelial cells

Pure iron is a candidate material for coronary artery stents because of its biodegradable and nontoxic properties. However the degradation characteristics of pure iron in vivo and in vitro are not yet clear. The purpose of the work described here was to determine the degradation rate of pure iron in vitro and to characterize the interaction of individual corrosion products from biocorrodible iron stents with endothelial cells (ECs) from the adjacent tissue. Pure iron was immersed in simulated body fluids (SBF) solution and the mass loss was measured. The response of human ECs to various concentrations of ferrous ions was investigated using WST-8 assay. The results demonstrate that the mean degradation rate of iron in vitro is about 20.4 μg/(cm² h). The lower iron concentration (< 10 μg/ml) may produce the favorable effect on the metabolic activity of ECs. Conversely, the very high iron ion concentration (> 50 μg/ml) may have cytotoxicity on ECs.