组织工程骨修复骨缺损的研究进展及临床应用

背景:随着生物技术的兴起,以生物材料来制作移植替代物的组织工程学正在不断地发展,因此组织工程骨修复骨缺损也成为当前的研究热点。目的:概述国际上关于骨组织工程研究的现状及临床应用的进展。方法:应用计算机检索PubMed数据库、Springer Link数据库、Science Direct数据库2000-01/2009-03文献,检索词为"tissue engineering of bone,bone defect,clinical applications"。选择与组织工程骨修复骨缺损相关的种子细胞、支架材料、动物模型、血管化和临床应用的文章,无论观察对象为人或动物均纳入检索标准。结果与结论:骨缺损的修复是临床上的难题之一,传统吻合血管的自体骨移植是治疗局部骨缺损的金标准,但是其存在供骨区并发症及数量有限的缺点。而无活性的异体骨虽然不受数量的限制,但是存在排异和传染疾病的可能。因此利用组织工程技术构建组织工程骨是修复骨缺损的趋势。组织工程骨包含具有骨传导性的支架、释放诱导成骨的生长因子、负载具有成骨潜能的细胞及组织工程骨血管化或充足的血供4个关键元素,因此要准确地评估组织工程骨修复骨缺损的作用,需要进一步理解参与骨再生的各种因素及其相互作用,同时还要在标准化动物模型研究中衡量积极因素和可能的有害影响。骨组织工程在实验研究领域已经显示出了积极的作用和相当大的发展前景,但在进入临床应用以前还有很多问题等待解决。     

大块血管化组织工程骨修复的骨缺损

背景:目前在构建较大体积组织工程骨方面还存在比较多的问题,其中最主要的就是缺血坏死。血管化的构建是保证大块组织工程骨生物学功能的关键因素。目的:制备大块血管化组织工程骨,行原位移植修复兔股骨干大面积缺损,探讨组织再生方式及特点。方法:建立仿兔股骨干结构支架材料内血管化预构模型,基于预构血管化支架,再构建大块血管化组织工程骨。18只8周龄新西兰大白兔分成实验组和对照组,实验组用大块血管化组织工程骨进行体内原位移植;对照组体内原位移植大块组织工程骨,未进行血管化处理。造模后2,4,8周通过大体观察、X射线片以及组织切片观察比较2组大块骨缺损的修复情况。结果与结论:大体观察及影像学观察结果均显示,造模后2,4,8周实验组的成骨情况均优于对照组。实验组兔造模后2,4,8周的新生骨组织占总移植骨面积比均显著高于对照组(P0.01)。提示修复大面积的骨缺损,采用大块血管化组织工程骨比单纯采用组织工程骨的效果更好。     

骨组织工程支架材料修复骨缺损的特性

目的:介绍各种骨组织工程支架的特性及在修复骨缺损中的作用。方法:以"骨组织工程,支架材料,骨缺损"为中文关键词;以:"bone tissue engineering,scafold,bone defect"为英文关键词,采用计算机检索2000-01/2010-06相关文章。纳入骨组织工程支架修复骨缺损相关的文章。选择28篇文献重点介绍各种骨组织工程支架的特性及在修复骨缺损中的特点。并应用硫酸钙人工骨进行验证。结果:用于骨组织工程的支架材料众多,目前,骨组织工程支架材料主要分为3类:生物衍生材料、无机材料和高分子材料,每种材料在修复骨缺损中都有各自的优缺点。随着研究的不断深入,复合支架材料成为目前的研究热点之一。一些具有生物活性的无机材料,如生物玻璃、羟基磷灰石已经被用来加入到胶原、壳聚糖的基体中来制备新型的骨组织工程复合支架材料。至今还未研制出一种理想的适于骨组织工程的支架材料。临床验证显示硫酸钙人工骨修复大块骨缺损效果较好。结论:相信随着各学科的发展,骨组织工程用支架材料的性能会越来越完善,从而促进骨组织工程的发展,最终应用于临床。     

骨组织工程的研究进展

目的：了解组织工程骨的相关概念及其特点,以及在组织工程骨研究中种子细胞、支架材料、生长因子、组织工程骨的构建及其应用的最新研究进展。方法：查阅相关中外文献,了解组织工程骨最新的发展动态及临床应用进展。结果：组织工程骨对骨缺损的修复是积极有效的。结论：随着研究的深入,骨组织工程技术最终会解决骨缺损的治疗这一骨外科领域的难题。     

组织工程骨材料在运动性骨缺损修复中的评价

目的：评价组织工程化人工骨材料的性能和应用,寻找合理的骨缺损修复材料。 方法：以“组织工程,骨缺损,人工骨,纳米材料” 为中文关键词;以“tissue engineering, bone defect, artificial bone, biological degradation”为英文关键词,采用计算机检索1993-01/2009-10相关文章。纳入与有关组织工程相关的文章;排除重复研究或Meta分析类文章。以30篇文献为主,重点进行了讨论组织工程纳米级人工骨材料的种类及其性能。 结果：可生物降解并具有生物活性的组织工程人工骨材料可作为一种较理想的支架材料应用于骨缺损修复组织工程。修复效果相当或接近自体骨,来源充足,既无免疫排斥反应,又避免取自体骨给患者带来的痛苦和并发症,不影响运动员重返赛场,运动员患者乐于接受。复合材料人工骨在解除运动员患者的后顾之忧的同时,也带来巨大的社会效益。基于纳米羟基磷灰石复合重组人骨形态发生蛋白2制成的支架,不但具有理想的生物相容性、生物降解性和较高的亲和性,而且能提高了骨诱导活性,能够促进新骨的形成。可生物降解并具有生物活性的组织工程人工骨材料在临床使用的初步情况表明,与人体生物相容性良好,无免疫排斥反应,愈合情况良好。 结论：骨缺损是常见的运动损伤,一直为运动损伤研究热点。组织工程化骨缺损修复的研究近年来发展迅速,为运动损伤骨缺损修复带来了契机。组织工程复合材料可以发挥不同材料的优势,弥补单一材料的不足,是一种比较理想的支架材料。     

骨缺损的显微外科修复治疗进展

对于各种原因所致的骨缺损的修复治疗一直是临床难题,也是国内外重大研究课题之一.从1820年德国医生Philips Von Walter开展有文献记载的第一例自体骨移植术以来,传统的游离自体骨移植至今仍然是临床上骨缺损修复治疗的常用方法,但其愈合主要是缓慢的"爬行替代"过程,仅适合修复较小的骨缺损.对大节段骨缺损,采用传统的无血供大块骨移植不但愈合时间长,且植骨大多数都存在不同程度的吸收或不可能被完全替代,效果并不理想,且肢体需长期固定,关节功能影响较大.随着显微外科技术的迅速发展,近20年来,带血管的骨移植广泛应用于骨缺损的修复治疗,取得良好的效果,成为骨缺损修复治疗中较为理想的方法.本文就这方面有关的进展综述如下.     

多细胞构建血管化组织工程骨在骨修复中的应用

背景:组织工程骨构建体的血管化性能不足是限制骨组织工程用于修复大尺寸骨缺损临床应用的主要挑战.目的:对近年来利用骨形成细胞和血管生成细胞构建组织工程构建体(基于支架或无支架)在骨修复中的应用进行了概述,以期实现组织工程骨可持续的血管生成及生成功能完善的血管,从而提高骨组织工程在大尺寸骨缺损修复应用中的细胞存活率、并为促...     

β-TCP材料改性研究进展及在骨缺损修复中的应用*

大段骨缺损再生修复是临床骨科面临的难题之一,利用组织工程材料修复大段骨缺损是最具前景的治疗方式。β-TCP材料由于具有与自体骨相似的无机成分,良好的生物相容性、可吸收降解以及骨传导等性能被广泛应用于骨科临床治疗。虽然β-TCP材料是一种最具潜力的骨替代材料,但是还存在诸如降解速率与新骨再生速率不匹配、脆性大力学强度不够、骨诱导能力差等缺陷,从而阻碍其临床应用。采用其他材料对β-TCP材料改性提高降解、力学及骨诱导等性能是目前研究热点。本文就β-TCP材料改性研究及在骨缺损再生修复中的应用作一综述。     

大块异体骨联合自体骨髓移植修复股骨上段肿瘤切除后缺损

背景：由于骨肿瘤切除造成的骨组织缺损是临床面临的难题之一,而如何修复缺损是骨科领域的热点问题。 目的：探讨采用大块异体骨联合自体骨髓移植治疗股骨上段肿瘤的临床应用及疗效。 方法：于2000-07/2005-06采用辐照冻存的大块异体骨联合自体骨髓移植治疗股骨上段良性肿瘤切除后遗留大块骨缺损12例,手术采用类似脊柱的“蛋壳”技术,掏空股骨头,保留股骨头圆韧带及头的皮质骨,尽量保留股骨头的1/3的血供,应用大块异体骨联合自体骨髓移植加内固定治疗。 结果与结论：患者术后随访6~11年。术后所有12例患者的大块异体骨联合自体骨髓在X射线中均显示整合血管化良好,骨小梁通过自体骨。MSTS93总体平均评分为26.33分,患者肢体功能总的优良率为83.3%。提示大块异体骨联合自体骨髓移植是修复股骨上段肿瘤切除后骨大块缺损的有效方法,并能充分整合成周围的自体骨。     

骨缺损的显微外科修复治疗进展

对于各种原因所致的骨缺损的修复治疗一直是临床难题,也是国内外重大研究课题之一。从1820年德国医生Philips Von Walter开展有文献记载的第一例自体骨移植术以来,传统的游离自体骨移植至今仍然是临床上骨缺损修复治疗的常用方法,但其愈合主要是缓慢的“爬行替代”过程,仅适合修复较小的骨缺损。对大节段骨缺损,采用传统的无血供大块骨移植不但愈合时间长,且植骨大多数都存在不同程度的吸收或不可能被完全替代,效果并不理想,且肢体需长期固定,关节功能影响较大。随着显微外科技术的迅速发展,近20年来,带血管的骨移植广泛应用于骨缺损的修复治疗,取得良好的效果,成为骨缺损修复治疗中较为理想的方     

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.     

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.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.