小口径人工血管支架材料:问题与前景

背景:小口径人工血管移植后远期通畅率的问题仍然是目前亟待解决的首要问题。目的:综述小口径人工血管支架材料及制备工艺、小口径人工血管的内皮化研究进展。方法:应用计算机检索Pubmed数据库(2000至2013年)和万方数据库(2003至2013年)相关文献,中文检索词为"人工血管,小口径,制备,静电纺丝,自组装,内皮化";英文检索词为"small-caliber,vascular graft,electrospun,layer-by-layer assembly,endothelialization"。共检索到文献125篇,保留其中41篇进行总结。结果与结论:目前已有的小口径血管支架材料包括天然生物材料、可降解高分子材料、复合材料及异种生物材料,小口径人工血管支架的制备技术主要有静电纺丝、自组装、快速成型、凝胶纺丝等。而促进小口径人工血管内皮化的方法有很多,不过每种方法都有其缺陷,不能从根本上解决远期通畅率问题。相信随着支架材料的制备技术更加成熟、多元化,人工血管内皮化研究的更进一步深入,小口径人工血管远期通畅率问题将逐步得到解决。     

小口径组织工程血管支架：如何产生一种具有生理重塑活性的材料

文题释义：小口径血管支架材料：①机械强度：包括生理的顺应性,即可承受长期的血流动力学压力,不会导致动脉瘤形成;②良好的生物相容性;③愈合时不会发生炎症、增生及纤维囊形成;④易于手术的操作和缝合;⑤低免疫原性。 丝素蛋白：存在于产丝节肢动物的腺体中,通过蜕变过程纺成纤维,是一种天然的生物衍生材料。其具有良好的机械性能、生物相容性、稳定化学性能等优点,因此丝素蛋白在血管组织工程领域中应用比较广泛。 背景：心血管疾病目前临床上常用的治疗方法是血管重建术,包括经支架介入治疗、冠状动脉旁路移植术和血管成形术。 目的：总结天然衍生支架材料、人工合成高分子材料和复合材料等组织工程血管支架材料的最新研究进展,为小口径血管置换提供理论依据。 方法：检索PubMed 数据库、万方数据库和中国全文期刊数据库2008年1月至2019年7月相关文献,以检索词为“组织工程;生物材料;支架材料;血管”“Tissue engineering,biological material,scaffold material,blood vessel”进行中英文检索。排除内容较陈旧及结论重复性文献,对最终入选的52篇文献进行探讨。 结果与结论：自体血管移植物,如隐静脉和胸内动脉,是小口径血管的最佳替代物,然而在移植后可能诱发血管腔再次狭窄,以及导致血栓形成、感染和移植失败发生率增加,因而严重阻碍在临床上的应用。考虑到存在的这些局限性,研究者将组织工程血管移植物嵌入细胞,从而产生一种具有生理重塑活材料,这一潜在的解决方案可为血管移植物的未来带来希望。 ORCID: 0000-0002-0841-0464(杨磊) 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     

丝素蛋白作为组织工程材料应用于角膜的研究进展

背景：丝素蛋白纤维材料具有透明性、结构可塑性、成分单一性、力学强韧性及生物相容性等特点。 目的：综述国内外丝素蛋白应用于角膜组织工程的研究进展。 方法：由第一作者在标题和摘要中以“silk fibroin, corneal, ocular”或“丝素,角膜”为检索词,检索1980至2011年PubMed及1990至2011年CNKI数据库中关于丝素蛋白角膜的文章。 结果与结论：从天然蚕丝中提取的高分子丝素蛋白,因其良好的生物相容性、独特的力学性能、光学透明性及降解速率可控性,既可以单独应用于角膜组织结构的重建,又可与其他组织材料联合应用,成为角膜组织工程学应用的理想材料。现已证明多种角膜细胞可在丝素纤维膜上良好生长,但体外培养的细胞应用于动物模型的相关研究较少;此外丝素蛋白材料植入角膜内对其产生何种影响的研究数据较缺乏,这些均是亟待解决的问题。     

丝素蛋白的生物相容性及临床应用

背景：皮肤损伤后的修复和重建都是棘手的问题,以皮肤细胞本身作为皮肤替代物修复缺损,以达到恢复组织器官的形态和功能,成为一种理想的途径,也是临床上难以解决的问题 目的：文章综述了丝素蛋白的生物相容性及应用的研究进展,寻找最佳人工皮肤以应用临床。 方法：应用计算机检索CNKI和PubMed数据库中1992-02/2011-03关于丝素蛋白生物相容性,在组织工程皮肤、生物材料领域应用的文章,在标题和摘要中以“丝素蛋白;生物相容性;组织工程;生物材料;应用”或“Silk fibroin;Biocompatibility;Tissue Engineering;Biological materials;Application”为检索词进行检索。选择文章内容与丝素蛋白的生物相容性及应用相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到215篇文献,根据纳入标准选择22篇文章进行综述。 结果与结论：对丝胶蛋白特性及研究应用的了解,有利于皮肤损伤后的修复和重建,以皮肤细胞本身作为皮肤替代物修复缺损,以达到恢复组织器官的形态和功能,有良好的机械性能和理化性质及有良好的生物相容性,对表皮细胞生长具有一定的促进作用。但将其应用于临床治疗方面仍需要很长的时间,尚有一些问题需要进一步研究、解决。     

骨科纳米生物材料的研究现状与展望

背景：随着纳米技术不断发展,越来越多的纳米技术已被应用到生物医药领域,为疾病诊断及治疗提供了很大的利益。 目的：综述纳米生物材料的研究现状及其在生物医学上的应用。 方法：由第一作者应用计算机检索中国期刊全文数据库、PubMed数据及万方数据库,2000年1月至2014年10月关于纳米生物材料、纳米生物陶瓷材料的文章,设定中文检索词为“纳米、生物陶瓷”,英文检索词为“nano, bioceramic”。 结果与结论：随着纳米技术的不断研究及开发,一些纳米技术已进入了实际应用阶段,应用纳米技术能够对疾病的发生、发展起防治作用。纳米陶瓷显著提高了材料的强度、韧性和超塑性,克服了生物陶瓷的许多不足,在骨科领域获得重要应用,比如有人工关节、人工骨骼、骨充填材料、骨置换材料、人工椎体等。 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     

组织工程支架在神经修复中的应用

背景：组织工程支架能够营造适当的神经再生微环境,富集神经再生所需的营养因子,促进轴突生长。 目的：综述近年来组织工程材料在神经损伤修复方面的科研进展。 方法：应用计算机检索PubMed数据库2009至2014年关于组织工程材料修复神经损伤的文章,检索词为“nerve regeneration, prostheses and implants”,并限定为“Full text”。同时利用计算机检索中国知网数据库2004至2014年相关方面的文章,检索词为“神经修复,材料”。 结果与结论：目前用于神经损伤的支架材料主要有天然材料、天然衍生材料、合成材料与复合材料,不同种材料具备各自的优点与缺点。通过化学交联剂或化学修饰,将天然衍生聚合物与其他天然或合成材料复合,可提高其理化和生物学特性,即复合材料神经支架取得的神经再生效果比单一材料效果好,因此当前的研究热点是复合材料。在临床研究方面,胶原蛋白基的神经修复支架材料已开始进入临床研究阶段。 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     

不同类型脑血管支架材料的特点及临床应用

背景：随着基础研究、临床应用,以及血管支架材料的不断发展,血管内支架置入治疗已被广泛应用于脑血管疾病治疗中。 目的：综述这几种支架材料的特点及临床应用情况。 方法：应用计算机检索CNKI数据库、万方数据库、PubMed数据库从建库到2014年3月的相关文献,中文检索关键词为“脑血管病,支架,生物相容性”,英文检索关键词为“cerebrovascular disease,stents,biocompatibility”。 结果与结论：按释放方式可将脑血管支架分为球囊扩张式支架与自膨式支架。最初应用的支架材料主要为裸金属材料,由记忆合金、医用不锈钢、钽、钴、镍钛合金等制成。由于金属支架置入后会释放金属离子,易致血栓形成,再狭窄率高,后来对其表面进行改性,出现了涂层支架与覆膜支架。支架置入治疗的围手术期并发症主要有过度灌注综合征、急性血栓形成、血管破裂和远端血管栓塞、血管痉挛和穿刺相关并发症,远期并发症主要是支架置入后再狭窄问题。相信随着科技的进步,支架材料和制作工艺的不断改进,血管支架置入治疗将更加安全有效。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：     

壳聚糖及其衍生物在软骨组织工程中的应用

背景：作为生物型支架,壳聚糖因其独特的多孔三维结构、易于改性的特征及良好的生物相容性成为了软骨组织工程支架材料的研究热点。 目的：就壳聚糖及其衍生物的设计、改性及在软骨组织工程中的应用作一综述。 方法：应用计算机检索PubMed数据库和CNKI数据库,中文关键词为“壳聚糖,壳聚糖衍生物,支架材料,组织工程,软骨组织”,英文检索词为“chitosan;chitosan derivatives;scaffold;tissue engineering;cartilage”,检索文献时间范围为1990年1月至2015年1月。 结果与结论：壳聚糖是一种天然的生物多糖,通过化学改性、共混改性等方法可以改变壳聚糖的溶解度、机械强度、生物活性甚至生物降解性等自身特性,从而制成更为合适的生物支架材料。进一步研究表明,将壳聚糖与种子细胞进行共同体外培养可以获得正常形态的软骨细胞并能合成特异性的细胞外基质成分,在动物体内,壳聚糖支架与种子细胞所构建的组织工程软骨能够修复软骨损伤,形成与周围正常软骨相似的组织。壳聚糖及其衍生物支架材料在软骨组织工程中有较为广阔的研究前景。  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     

丝素蛋白材料在组织工程中的新进展

背景：丝素蛋白支架已被建议运用在组织工程骨和软骨重建、肌腱重建、血管重建,神经重建以及膀胱重建等各方面。 目的：总结丝素蛋白作为支架在生物材料和组织工程领域的应用与发展。 方法：由第一作者应用计算机检索PubMed数据库及中国期刊数据库2000年1月至2011年11月有关丝素蛋白支架制备工艺,丝素蛋白支架修饰方法及丝素蛋白在组织工程中的应用等方面的文献。 结果与结论：丝素蛋白具有机械强度高、生物降解性慢、生物相容性良好、制备工艺多样等特点,支持多种细胞黏附、分化和生长,可应用于人工韧带、血管、骨、神经组织等方面。近期以丝素蛋白支架作为载体,通过多种方式添加各种生物制剂,比如各种生长因子和细胞因子,进一步扩大丝素蛋白在组织工程中的应用范围。     

骨组织工程支架材料的研究现状与应用前景

背景：目前组织工程骨修复骨缺损在临床应用中较为关键的问题是建立血管网,为新骨的形成提供氧气及营养物质,并为机体提供代谢途径。 目的：综述近年组织工程骨支架材料的特点,并着重介绍复合支架材料的研究现状。 方法：以“骨组织工程,血管化,支架材料,复合支架材料”为中文检索词,以“bone tissue engineering, vascularization,scaffold,composite scaffold”英文检索词,应用计算机在中国期刊全文数据库和PubMed数据库检索2001年1月至2014年1月的相关文章,将所有文章进行初步筛选后,对保留的文章进一步详细分析、归纳并总结。 结果与结论：按照组织工程骨支架材料的来源不同,可将其分为人工合成材料、天然衍生材料和复合支架材料,单一支架材料难以作为最理想的材料修复骨缺损,复合支架材料能在不同程度上弥补单一支架材料的缺陷,因此近年来组织工程支架材料的发展由单一材料发展为复合材料,并呈现人工合成材料与天然材料有机结合的趋势。但复合支架材料在临床应用中仍然有许多尚待解决的问题,主要有控制复合材料比例,使材料降解速率与组织细胞的生长速率相适应,保持复合材料的多孔隙和高机械强度。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：     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Role of cholinergic and serotoninergic processes in modulation of activity of the negative reinforcement system

The effect of cholinergic and serotoninergic drugs on the latency of blocking of central aversive stimulation was studied. Physostigmine and fluoxetin increased the latency of avoidance. Hyoscine and n-chloramphetamine could either increase or decrease the time of active avoidance. Fluoxetin reduced the activating and reversed the depriming effects of hyoscine. A combination of fluoxetin with physostigmine potentiated the depressant effect of the latter. n-Chloramphetamine weakened inhibitory effect of physostigmine and potentiated the action of hyoscine. An inhibitory role is suggested for cholinergic and serotoninergic mechanisms in the activity of the negative reinforcement system. Functional interconnection between these neuromediator systems is postulated.Department of Pharmacology, Academician I. P. Pavlov First Medical Institute, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 552–554, November, 1978.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting

Tumors are angiogenesis dependent. Some chemotherapeutics have been shown to be able to suppress angiogenesis and thus tumor growth in vivo at low, well-tolerated doses. Not much is known about the angiogenesis-modulating effects of chemotherapeutics in vivo, however. Microvessel sprouting is inherent to angiogenesis. Using the rat mesentery assay, we studied the effect of cyclophosphamide, doxorubicin and paclitaxel at a low, atoxic dose on the number of sprouts per unit tissue volume (No. SP) and their length (Le. SP) at the edge of the expanding network in VEGF165-mediated angiogenesis. A single dose of each cytotoxic drug was administered i.v. 7 days before the animals were sacrificed. Cyclophosphamide significantly lengthened the shortest Le. SP and shortened the longest Le. SP, doxorubicin did not significantly affect Le. SP, whereas paclitaxel significantly shortened both the shortest and the longest Le. SP. No correlation was found between the present results and the distinctly drug-specific results of microvessel segment number and length analyzed within central parts of the same expanding network. To our knowledge, this is the first quantitative report on the effect of chemotherapy on angiogenesis sprouting in vivo. Collectively, the data suggest that cyclophosphamide, doxorubicin and paclitaxel at a non-toxic dose primarily target different intrinsic components of the angiogenic cascade, leading to distinctly drug-specific effects.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Experimental study of the possibility of metabolic correction of maternal, fetal, and newborn hypoxia in rats using a new amino acid composition MR-33

The status of pregnant rats, their fetuses, and progeny exposed to oxygen insufficiency are compares. By the end of pregnancy the resistance to hypoxia markedly decreases. Newborn rats during nursing are highly resistant to hypoxia. When nursing period is over, the resistance to hypoxia drops, but later is gradually restored. MR-33 preparation produces a pronounced antihypoxic effect. Administration of the drug to pregnant rats not only appreciably improves their resistance to oxygen insufficiency, but also promotes adaptation and compensatory mechanisms in the progeny, thus helping the progeny to better tolerate hypoxia, particularly when its probability is particularly high. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 451–454, October, 1997     

Changes in state of the surfactant in experimental pneumonia

The state of the lung surfactant in rabbits at different stages of development of experimental pneumonia (3–60 days) was compared with the dynamics of oxidoreductases in the alveolar epithelium and cells of the inflammatory focus of infiltration. In the initial stage (3–7 days) of activation of cell metabolism there was a brief increase in, the intensity of surfactant lipid synthesis, accompanied by relative inhibition of phospholipid synthesis. Later, development of degenerative changes and sclerosis of the parenchyma was accompanied by inhibition of synthesis of all components of the surfactant. The surface activity of the surfactant became stabilized at a low level.Laboratory Division, I. M. Sechenov Research Institute of Medical Climatology and Physical Methods of Treatment, Yalta. Department of Pathological Anatomy, Faculty of Internal Medicine, and Department of Organic Chemistry, Crimean Medical Institute, Simferopol'. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 286–288, September 1977.     

Response of different types of connective tissue to hormones

A comparative study was made of the lysosomal glycosidases of the eye tissues (sclera and cornea) and also of bone tissue and cartilage from rabbits. Intraperitoneal injection of thyrocalcitonin (TCT), deoxycorticosterone (DOC), hydrocortisone (HC), and somatotropic hormone (STH) were shown to modify the activity of -galactosidase, -glucosidase, and hyaluronidase and the functional state of the lysosomal membranes in the tissues. HC and STH stabilize, whereas DOC and large doses of TCT labilize the lysosomal membranes. After injection of HC and STH the absolute activity of the enzymes in the tissue homogenates falls, whereas DOC has the opposite action.Helmholtz Research Institute for Eye Diseases, Moscow. N. N Priorov Central Scientific-Research Institute of Traumatology and Orthopedics, Moscow. (Presented by Academicial of the Academy of Medical Sciences of the USSR M. V. Volkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 7, pp. 38–41, July, 1977.     

Hypermethioninemias of genetic and non-genetic origin: A review

This review covers briefly the major conditions, genetic and non-genetic, sometimes leading to abnormally elevated methionine, with emphasis on recent developments. A major aim is to assist in the differential diagnosis of hypermethioninemia. The genetic conditions are: (1) Homocystinuria due to cystathionine β-synthase (CBS) deficiency. At least 150 different mutations in the CBS gene have been identified since this deficiency was established in 1964. Hypermethioninemia is due chiefly to remethylation of the accumulated homocysteine. (2) Deficient activity of methionine adenosyltransferases I and III (MAT I/III), the isoenzymes the catalytic subunit of which are encoded by MAT1A. Methionine accumulates because its conversion to S-adenosylmethionine (AdoMet) is impaired. (3) Glycine N-methyltrasferase (GNMT) deficiency. Disruption of a quantitatively major pathway for AdoMet disposal leads to AdoMet accumulation with secondary down-regulation of methionine flux into AdoMet. (4) S-adenosylhomocysteine (AdoHcy) hydrolase (AHCY) deficiency. Not being catabolized normally, AdoHcy accumulates and inhibits many AdoMet-dependent methyltransferases, producing accumulation of AdoMet and, thereby, hypermethioninemia. (5) Citrin deficiency, found chiefly in Asian countries. Lack of this mitochondrial aspartate-glutamate transporter may produce (usually transient) hypermethioninemia, the immediate cause of which remains uncertain. (6) Fumarylacetoacetate hydrolase (FAH) deficiency (tyrosinemia type I) may lead to hypermethioninemia secondary either to liver damage and/or to accumulation of fumarylacetoacetate, an inhibitor of the high K(m) MAT. Additional possible genetic causes of hypermethioninemia accompanied by elevations of plasma AdoMet include mitochondrial disorders (the specificity and frequency of which remain to be elucidated). Non-genetic conditions include: (a) Liver disease, which may cause hypermethioninemia, mild, or severe. (b) Low-birth-weight and/or prematurity which may cause transient hypermethioninemia. (c) Ingestion of relatively large amounts of methionine which, even in full-term, normal-birth-weight babies may cause hypermethioninemia.