镍钛形状记忆合金血管内支架组织相容性实验研究

将锥形记忆合金支架分别植入６只猪右侧髂动脉。用以研究镍钛形状记忆合金血管内支架生物相容性，支架植入前入植入后８个月，观测动物血常规，肝肾功能以及毛发中镍钛元素含量，均无明显变化（Ｐ〉０．０５），支架植入后８个月处死动物，全身重要脏器（肝、脾、肾、肺、心、脑等）病理学检查结构正常，无淋巴细胞和单核细胞浸润，支架植入部位上游血管壁内膜光滑，内皮细胞结构正常，内弹力板完整，支架植入段为完整肉芽组织阻塞，     

天然生物材料构建组织工程支架的研究进展

细胞培养支架材料是组织工程的重要研究内容之一.本文综述近年来几种典型天然生物材料构建组织工程支架的研究进展,并详细介绍了适用于天然生物材料制备组织工程支架的致孔方法.     

血管支架内再狭窄的研究进展

冠状动脉粥样硬化性心脏病是心血管疾病死亡的重要原因之一 ,血管支架植入治疗已经成为一个标准的血管成形术方法 ,但是支架内再狭窄仍然是制约其应用的一个主要的问题 ,据统计 ,冠状动脉血管支架植入在 6个月后的再狭窄率仍然高达 2 0～ 30 % ,成为制约支架临床应用的一个最主要的问题。本研究综述了血管支架内再狭窄机理以及再狭窄发生过程的研究进展 ,介绍了金属支架涂层以及高分子血管支架的最新研究进展。     

组织工程血管支架材料的研究与进展

BACKGROUND: Tissue-engineered vascular scaffold materials have been developed from pure natural materials to degradable composite materials and nano polymer materials, and the preparation method has also been developed from the manual technology to the rapid proto-typing technology. OBJECTIVE: To clarify the advantages and disadvantages, application and research hotspots of different tissue-engineered vascular scaffold materials, and to find a suitable scaffold material for clinical treatment. METHODS: The first author retrieved databases of PubMed, CNKI and CqVip for relevant articles about tissue-engineered vascular scaffolds published from 1985 to 2015. The key words were “tissue engineering, tissue engineered, blood vessel, vascular, scaffold” in English and Chinese, respectively. In accordance with the inclusion and exclusion criteria, 36 articles were reviewed. RESULTS AND CONCLUSION: Non-degradable materials are mainly used to construct large diameter  tissue-engineered blood vessels. Natural biomaterials have good biocompatibility, which can provide necessary signals for cells and promote cell attachment and retain cell differentiation ability. Degradable polymer composite materials have good biocompatibility, whose mechanical properties, degradation rate and microstructure can be controlled, and they can be mass-produced according to the design requirements. The composite materials inheriting the advantages of natural biomaterials and synthetic polymer materials have become the most ideal scaffold materials and will be a research focus in the future.     

国产钛镍合金血管支架的生物相容性研究

采用国产钛镍形状记忆合金制成４ｍｍ内径的血管支架,通过导管置入８只正常犬的双侧髂动脉。观察１－６个月,发现支架表面业层新生内膜覆盖,光镜及电观察新生内膜表层为血管内皮样细胞,国产钛镍合金血管要有很好的生物相容性     

重组蛛丝蛋白支架材料在大鼠体内的组织相容性

目的 探讨基因重组蛛丝蛋白等4种支架材料在大鼠体内的组织相容性.方法 按照生物材料生物学评价试验国家标准进行4种材料的动物体内植入实验,通过大体观察和组织学方法对4种材料进行检测评价.结果 4种材料组织相容性优良顺序为pNSR16、pNS2、PVA、pNSR-Z.pNSR16和pNS2支架材料均显示出良好的组织相容性.结论 重组蛛丝蛋白有良好的组织相容性,其应用于组织工程的前景是广阔的.     

重组蛛丝蛋白支架材料在大鼠体内的组织相容性

目的探讨基因重组蛛丝蛋白等4种支架材料在大鼠体内的组织相容性。方法按照生物材料生物学评价试验国家标准进行4种材料的动物体内植入实验,通过大体观察和组织学方法对4种材料进行检测评价。结果4种材料组织相容性优良顺序为pNSR16、pNS2、PVA、pNSR-Z。pNSR16和pNS2支架材料均显示出良好的组织相容性。结论重组蛛丝蛋白有良好的组织相容性,其应用于组织工程的前景是广阔的。     

一种新型的脱细胞组织工程血管支架的构建和评价

本研究的目的是制备一种免疫原性较小、生物相容性较好、力学性能优良的组织工程血管支架。新鲜获得的犬主动脉,置于三蒸水中4℃过夜，使血管细胞由于渗透压差较大而破裂；随后经过多聚环氧化合物家族的乙二醇缩水甘油醚（EX-810）的作用。进一步促进细胞破裂的同时。对血管支架的纤维结构起交联作用；最后应用物理超声的方法清除支架内的细胞碎片残留。用这种方法处理的犬主动脉内几乎没有可见的核染，基本消除了血管支架的免疫原性。同新鲜的血管相比较。这种组织工程血管支架的各种力学指标与新鲜的犬主动脉没有显著差异。说明处理后的支架仍然保持新鲜血管的力学特征。同时它还表现出极低的细胞毒性。分别在支架上种植内皮细胞和平滑肌细胞，扫描电镜检测结果表明，两种细胞在支架上生长良好，且局部已经融合成片。 相容性     

组织工程与生物材料

介绍了组织工程的原理、研究现状,以及相关生物材料的基本概念和生物材料的发展概况.指出目前组织工程的研究为生物材料提供了极大的发展机会,认为可降解生物材料是组织工程用支架材料的研究重点,未来组织工程相关生物材料的发展方向是仿生化和智能化,组织工程学的发展将会促进材料的发展,并将由此产生巨大的社会效益和经济效益.     

砷涂层支架置入后的血管组织相容性

背景：研究认为,三氧化二砷可以抑制血管平滑肌细胞的增殖,促进其凋亡,那么砷对血管平滑肌细胞的增生是否也有同样的抑制作用,砷涂层血管支架能否与血管组织相容,早期较好地被血管内膜覆盖或达到减少内膜过度增生的作用？ 目的：观察砷涂层血管支架的血管组织相容性。 方法：取大耳白家兔14只,随机分为2组,分别在腹主动脉处植入砷涂层316 L不锈钢支架和316 L不锈钢裸支架,植入28 d后结扎支架部位血管的远端和近端,取下支架部位的血管行苏木精-伊红染色,光镜检查。 结果与结论：①大体观察：支架处的血管外径稍大于相邻处血管的外径,呈扩张状态,无肉眼可见的血栓,切开支架,支架表面可见光滑的新生内膜形成,新生内膜表面光滑。②光镜观察：支架丝位于血管的中层,中层平滑肌被压,支架丝周边,血管内膜平滑肌增生,使血管内膜增厚。支架丝的血管腔面可见新生的血管内膜形成并覆盖支架丝,支架丝与血管组织之间可见一薄层黑色物质,为涂层药物砷及其化合物,证明砷涂层支架可以被血管组织覆盖,具有良好的血管组织相容性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Review: advances in vascular tissue engineering using protein-based biomaterials

The clinical need for improved blood vessel substitutes, especially in small-diameter applications, drives the field of vascular tissue engineering. The blood vessel has a well-characterized structure and function, but it is a complex tissue, and it has proven difficult to create engineered tissues that are suitable for widespread clinical use. This review is focused on approaches to vascular tissue engineering that use proteins as the primary matrix or "scaffold" material for creating fully biological blood vessel replacements. In particular, this review covers four main approaches to vascular tissue engineering: 1) cell-populated protein hydrogels, 2) cross-linked protein scaffolds, 3) decellularized native tissues, and 4) self-assembled scaffolds. Recent advances in each of these areas are discussed, along with advantages of and drawbacks to these approaches. The first fully biological engineered blood vessels have entered clinical trials, but important challenges remain before engineered vascular tissues will have a wide clinical effect. Cell sourcing and recapitulating the biological and mechanical function of the native blood vessel continue to be important outstanding hurdles. In addition, the path to commercialization for such tissues must be better defined. Continued progress in several complementary approaches to vascular tissue engineering is necessary before blood vessel substitutes can achieve their full potential in improving patient care.     

不同材料构建组织工程软骨及支架的应用

背景：组织工程技术的发展为软骨的再生和修复提供了新的途径,根据软骨自身的结构和特点,作为人工软骨的替代材料和支架材料应具有良好的生物力学性能。 目的：总结运动性关节软骨损伤修复材料及其支架材料的应用进展及其生物替代材料的生物力学特征,评价目前组织工程软骨材料应用的性能及发展前景。 方法：以“组织工程;软骨组织;支架材料;生物相容性”为关键词,应用计算机检索维普数据库和PubMed数据库中1990-01/2011-04关于组织工程软骨应用研究的文章,纳入与有关生物材料与组织工程软骨相关的文章;排除重复研究或Meta分析类文章。以24篇文献为主重点进行了讨论组织工程软骨材料的种类、性能及其应用效果和前景。 结果与结论：目前关节软骨修复领域以自体软骨移植效果为最佳,骨髓基质干细胞在离体试验及动物实验中研究较多,在临床应用中较少,尚在探索阶段。支架材料的应用比较繁复,天然材料、人工合成材料以及复合材料都存在一定的不足,虽然复合材料成为研究的热点,但是某些性能并不能很好地符合支架要求,并且在机体内这些材料所带来的长期影响还不能预见,这就迫切需要新材料的出现,来更好地满足组织软骨织支架的要求,达到修复和重建的目的。 关键词：软骨;组织工程;软骨组织;种子细胞;支架材料 doi:10.3969/j.issn.1673-8225.2012.08.036     

覆膜支架在颅颈血管病变治疗中的应用

背景：随着微导管技术的不断完善和栓塞材料的改进,血管内介入治疗已成为治疗颅颈血管病变的首选方法,主要包括可脱球囊、弹簧圈、液体栓塞剂、覆膜支架。与其他血管内栓塞治疗技术相比,覆膜支架有2个突出优点：有较高的完全闭塞率和较低的再通率。 目的：介绍国内主要应用的几种覆膜支架,以及覆膜支架治疗颅颈动脉瘤和颈内动脉海绵窦瘘的临床效果。 方法：以“覆膜支架,生物相容性,动脉瘤,颈动脉海绵窦瘘”为关键词,采用计算机检索万方数据网1998-01/2010-12相关文章。纳入覆膜支架治疗颅颈血管病变方面的文献,排除重复研究或Mata分析类文章。 结果与结论：现在神经外科临床应用的覆膜支架,主要采用的是美国Abbott公司推出的Jostent覆膜支架和上海微创公司生产的Willis覆膜支架。Jostent覆膜支架优点是生物相容性和扩展性较好,其多微孔结构可减少细胞扩散,阻止血小板聚集、炎性细胞移动,从而降低了继发性血栓及血管狭窄的概率;其缺点是在颅内动脉中应用的范围比较狭窄,动脉不能过于迂曲,弯曲角度不能过于锐利,病变附近不能有不可闭塞的穿支或分支。专为颅内血管设计的Willis覆膜支架的应用,彻底改变了颅内动脉瘤血管内治疗的传统理念,整个支架系统具有一定的柔顺性,有助于其通过颅内弯曲的血管系统,尤其是颈内动脉虹吸段,由于其操作简单,效果满意,为血管内治疗技术的发展提供了新的方向。     

不同生物材料修复跟腱损伤的应用

背景：构建组织工程化肌腱的关键是寻找适于肌腱细胞黏附、生长及功能分化的支架材料。 目的：评价不同生物材料在跟腱损伤修复中的效果。 方法：以“生物材料,跟腱,修复” 为关键词在万方数据库中检索1985-01/2011-01关于生物材料治疗跟腱缺损的文章。 结果与结论：陈旧性跟腱断裂难以自行愈合及修复,易遗留疼痛及功能障碍。长期以来,不少学者对跟腱缺损的治疗进行了较多的研究,从自体肌腱移植、同种异体肌腱移植到人工肌腱移植、组织工程肌腱移植等,实践证明这些方法手段都存在一定的优点和缺点。虽然肌腱组织工程中支架材料的研究与应用已经取得了一些成功,但是目前应用的材料或存在生物相容性问题、降解性问题或存在力学性能差、难加工成型等缺陷,与理想的支架材料还存在很大差距。     

血管内皮细胞在生物材料引起血栓形成过程中的作用

血管内皮细胞——这一铺展于血管内腔、包绕着循环血的细胞,可合成和释放多种活性物质调节血液的凝血与抗凝平衡,在生物材料引起血栓形成的过程中起着重要的作用。同时它促栓和抗栓功能的异常改变也是衡量生物材料血液相容性优劣的灵敏指标。本文就近年来对内皮细胞对凝血—抗凝系统的调节及其在生物材料引起血栓形成中的作用等方面的研究以及尚待解决的一些问题作一综述。     

Mechanical property characterization of electrospun recombinant human tropoelastin for vascular graft biomaterials

The development of vascular grafts has focused on finding a biomaterial that is non-thrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of native vessels and allows for regeneration of arterial tissue. In this study, the structural and mechanical properties and the vascular cell compatibility of electrospun recombinant human tropoelastin (rTE) were evaluated as a potential vascular graft support matrix. Disuccinimidyl suberate (DSS) was used to cross-link electrospun rTE fibers to produce a polymeric recombinant tropoelastin (prTE) matrix that is stable in aqueous environments. Tubular 1 cm diameter prTE samples were constructed for uniaxial tensile testing and 4 mm small-diameter prTE tubular scaffolds were produced for burst pressure and cell compatibility evaluations from 15 wt.% rTE solutions. Uniaxial tensile tests demonstrated an average ultimate tensile strength (UTS) of 0.36 ± 0.05 MPa and elastic moduli of 0.15 ± 0.04 and 0.91 ± 0.16 MPa, which were comparable to extracted native elastin. Burst pressures of 485 ± 25 mm Hg were obtained from 4 mm internal diameter scaffolds with 453 ± 74 μm average wall thickness. prTE supported endothelial cell growth with typical endothelial cell cobblestone morphology after 48 h in culture. Cross-linked electrospun rTE has promising properties for utilization as a vascular graft biomaterial with customizable dimensions, a compliant matrix and vascular cell compatibility.     

Mechanisms of vascular endothelial growth factor-induced pathfinding by endothelial sprouts in biomaterials

A critical property of biomaterials for use in regenerative medicine applications is the ability to promote angiogenesis, the formation of new vascular networks, to support regenerating tissues. Recent studies have demonstrated that a complex interplay exists between biomechanical and biochemical regulators of endothelial cell sprouting, an early step in angiogenesis. Here, we use a microfluidic platform to study the pathfinding behaviors induced by various stable vascular endothelial growth factor (VEGF) gradients during sprouting morphogenesis within biomaterials. Quantitative, time-lapse analysis of endothelial sprouting demonstrated that the ability of VEGF to regulate sprout orientation during several stages of sprouting morphogenesis (initiation, elongation, and turning navigation) was biomaterial dependent. Identical VEGF gradients induced different types of coordinated cell movements depending on the density of the surrounding collagen/fibronectin matrix. In denser matrices, sprouts were more likely to have an initial orientation aligned parallel to the VEGF gradient. In contrast, in less dense matrices, sprouts were more likely to initially misalign with the VEGF gradient; however, these sprouts underwent significant turning and navigation to eventually reorient to be parallel to the VEGF gradient. These less dense matrices required shallower VEGF gradients and demonstrated lower activating VEGF thresholds to induce proper sprout alignment and pathfinding. These results encourage the future use of microfluidic platforms to probe fundamental aspects of matrix effects on angiogenesis, to screen biomaterials for angiogenic potential, and to design ex vivo tissues with aligned vascular networks.     

A comparative study of three different biomaterials in the engineering of skeletal muscle using a rat animal model

Defects caused by traumatic or postsurgical loss of muscle mass may result in severe impairments of the functionality of skeletal muscle. Tissue engineering represents a possible approach to replace the lost or defective muscle. The aim of this study was to compare the suitability of three different biomaterials as scaffolds for rat myoblasts, using a new animal model. PKH26-fluorescent-stained cultured rat myoblasts were either seeded onto polyglycolic acid meshes or, alternatively, suspended in alginate or in hyaluronic acid-hydrogels. In each of the eight Fisher CDF-344 rats, four capsule pouches were induced by subcutaneous implantation of four silicone sheets. After two weeks the silicone sheets were removed and myoblast-biomaterial-constructs were implanted in the preformed capsules. Specimens were harvested after four weeks and examined histologically by H&E-staining and fluorescence microscopy. All capsules were well-vascularized. Implanted myoblasts fused by forming multinucleated myotubes. This study demonstrates that myoblasts seeded onto different biomaterials can be successfully transplanted into preformed highly vascularized capsule pouches. Our animal model has paved the way for studies of myoblast-biomaterial transplantations into an ectopic non-muscular environment.     

Survival and differentiation of embryonic neural explants on different biomaterials

Biomaterials prepared from polyacrylamide, ethyl acrylate (EA), and hydroxyethyl acrylate (HEA) in various blend ratios, methyl acrylate and chitosan, were tested in vitro as culture substrates and compared for their ability to be colonized by the cells migrating from embryonic brain explants. Neural explants were isolated from proliferative areas of the medial ganglionic eminence and the cortical ventricular zone of embryonic rat brains and cultured in vitro on the different biomaterials. Chitosan, poly(methyl acrylate), and the 50% wt copolymer of EA and HEA were the most suitable substrates to promote cell attachment and differentiation of the neural cells among those tested. Immunofluorescence microscopy analysis showed that progenitor cells had undergone differentiation and that the resulting glial and neuronal cells expressed their intrinsic morphological characteristics in culture.