组织工程心脏瓣膜的构建：现状与前景

背景：目前临床上应用的心脏生物瓣和机械瓣都存在一些缺陷和不足,而组织工程心脏瓣膜有可能避免这些问题的出现,成为瓣膜替代物的理想选择。 目的：探讨构建组织工程心脏瓣膜的实验研究进展。 方法：应用数据库检索的方法分析关于组织工程心脏瓣膜的实验研究文献,组织工程心脏瓣膜的三大要素为种子细胞、支架材料和细胞种植。 结果与结论：心脏瓣膜修复和置换是目前治疗心脏瓣膜性疾病的主要外科手段。目前,主要用于构建组织工程心脏瓣膜的种子细胞有血管内皮细胞、内皮祖细胞以及骨髓间充质干细胞等。经脱细胞处理的支架具有良好的生物力学性能和组织相容性,细胞种植后支架表面会形成一层连续的细胞层,其构建的组织工程心脏瓣膜是可行的。组织工程心脏瓣膜有着良好的应用前景,但目前还有很多问题需要解决,还处于研究的初级阶段。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

脂肪干细胞与Bio-oss支架构建组织工程骨治疗种植体周围骨缺损

背景：目前治疗种植体周围炎的方法主要有手术治疗、激光治疗、超声洁治加局部用药单独或联合治疗等,但并未完全达到理想的治疗效果。 目的：探讨由骨形态发生蛋白修饰的脂肪干细胞与Bio-oss支架构建组织工程骨治疗种植体周围炎性骨缺损的可行性。 方法：应用计算机检索1988年1月至2011年12月Pubmed数据库相关文章,检索词为“adipose-derived stem cells、tissue engineering”,并限定文章语言种类为英文。同时计算机检索2005年1月至2011年12月CNKI数据库相关文章,检索词为“脂肪干细胞、种植体周围炎”,并限定文章语言种类为中文。共检索到文献56篇。 结果与结论：利用组织工程原理与方法再生组织的特点和优势,将脂肪干细胞作为理想的种子细胞,骨形态发生蛋白2作为理想的细胞因子与Bio-oss生物材料混合,构成三维环境,Bio-oss晶体内广泛交织的空隙结构,有利于脂肪干细胞的迁移。骨形态发生蛋白2与脂肪干细胞复合,促进控制其分化向骨形成中心募集,并分化为骨系细胞,通过钙盐沉积形成新骨,达到治疗种植体周围骨缺损的目的。     

不同来源干细胞移植治疗炎症性肠病

背景：干细胞移植后可迁移至受损肠道参与损伤组织修复和功能重建,并可恢复肠道正常的免疫功能。 目的：综述不同来源干细胞移植治疗炎症性肠病的研究进展。 方法：应用计算机检索1990/2008 PubMed数据库相关文章,检索词为“stem cells,tissue engineering,biliary complications,intestinal disease,human intestinal tract”,并限定文章语言种类为English。同时计算机检索1990/2008万方数据库相关文章,检索词为“干细胞,组织工程,肠道疾病,人工肠道”,并限定文章语言种类为中文。最终纳入符合标准的文献24篇。 结果与结论：目前炎症性肠病的治疗在于控制活动性炎症和调节免疫紊乱,包括抗炎药物、激素、免疫抑制剂、生物治疗等多种治疗手段,但无一具有长期疗效且不良反应颇多,而近年来干细胞再生、营养、免疫调节等方面的研究给肠性疾病相关治疗带来了新希望,其多向分化潜能、免疫调节作用、营养作用使干细胞移植有望成为肠道疾病治疗的有效途径,干细胞和组织工程在肠道的研究有十分广阔的应用前景。     

组织工程心脏瓣膜种子细胞:来源及应用

背景:应用机械瓣和生物瓣行瓣膜置换是治疗终末期瓣膜病的有效手段,然而他们的临床应用受到多个因素的限制。具备生物活性的组织工程心脏瓣膜有潜力克服机械瓣和生物瓣的不足,选择适宜的种子细胞是组织工程心脏瓣膜研究的一个重要方面,许多成熟的体细胞和干细胞已被用于构建组织工程心脏瓣膜,然而尚未获得理想的结果。目的:以构成瓣膜的细胞成分为基础,对用于构建组织工程心脏瓣膜的种子细胞、体外细胞种植方法的研究进行综述。方法:由第一作者基于PubMed数据库和万方数据库应用计算机检索2000年1月至2012年12月相关的文章,英文检索词为"Tissue engineering,Heart valves,Cell",中文检索词为"组织工程,心脏瓣膜,细胞",优选文章内容与组织工程心脏瓣膜种子细胞直接相关,具备针对性和权威性,发表在权威杂志的文章共39篇进行综述。结果与结论:瓣膜的细胞成分主要是内皮细胞和间质细胞,早期人们常用内皮细胞和成纤维细胞构建组织工程瓣膜,随着干细胞研究的深入,应用搏动性生物反应器种植间充质干细胞具有构建的组织工程瓣膜的潜力。     

涂层材料及技术在医学临床领域的应用

背景：涂层材料及技术已在人们的生产生活中广泛应用,在医学领域里也得到了蓬勃发展。 目的：综述涂层材料及技术在医学领域中的应用进展。 方法：应用计算机检索2000-01/2010-12万方数据库相关文章,检索词“涂层,医学,应用”,并限定文章语言种类为中文。同时计算机检索2000-01/2010-12 PubMed数据库相关文章,检索词“coating,medicine,application”,并限定文章语言种类为English。共检索到文献614篇,最终纳入符合标准的文献30篇。 结果与结论：涂层技术在生活的方方面面都有应用,在医学领域里的应用也日渐蓬勃,目前研制出了很多生物相容性好排斥反应小的涂层材料并应用于临床。文章分别从口腔、体外循环、骨科等领域对涂层支架进行介绍,发现开发新的涂层药物,寻找更加合理有效的药物组合,可能会使药物涂层支架的治疗作用产生质的飞跃。     

生物材料生物相容性的评价方法和发展趋势

背景：对生物材料进行生物相容性的评价是进入临床实验前的重点研究内容,但是目前国内外标准的评价体系尚未完全建立,影响了生物材料的研究。 目的：对生物材料生物相容性的评价方法进行回顾和展望。 方法：应用计算机检索2000-01/2010-08 PubMed数据库相关文章,检索词为“biomaterials,biocompatibility,evaluated methods,trend”,并限定文章语言种类为English。同时计算机检索2000-01/2010-08中国期刊网全文数据库(CNKI)相关文章,检索词为“生物材料,生物相容性,评价方法,研究进展”,并限定文章语言种类为中文。共检索到文献104篇,最终纳入符合标准的文献25篇。 结果与结论：生物材料必须具有良好的生物相容性才能确保临床应用的安全性。生物材料不引起明显的临床反应以及能耐受宿主各系统的作用而保持相对稳定、不被破坏和排斥的生物学性质则为生物相容性良好。生物相容性的评价是生物材料进入临床实验前必不可少的关键环节。随着分子生物学的迅速发展,生物材料生物相容性的评价方法研究手段逐渐多样化,其评价已从整体、细胞水平进入了分子水平。     

组织工程心脏瓣膜支架材料的研究与进展

背景:组织工程心脏瓣膜有望克服生物瓣膜和机械瓣膜的缺点而从根本上解决瓣膜病外科面临的问题。其中,支架材料扮演着关键角色,而选择何种支架材料是经常困扰研究者的难题。目的:文章在强调细胞外基质与细胞的相互作用在组织动力学中有重要作用的基础上,对目前广泛使用的支架材料及其优缺点进行简要综述。方法:使用Pubmed文献检索数据库,采用医学主题词检索,检索词为"心脏瓣膜;组织工程",时间范围为2000-01/2009-08,语言限定为英文。共检索到186篇文章,其中综述34篇,实验研究152篇。选择文章主要内容与组织工程心脏瓣膜支架材料直接相关的、针对性强、代表性好、相关领域权威杂志的文章共39篇进行综述。结果与结论:天然支架材料因其优越的生物相容性和三维空间构象,具有其他材料不可比拟的仿生性。合成可降解高分子材料具有良好的可控性和力学性能也备受研究者青睐,而将天然材料和高分子材料融合一体构建的复合支架材料为组织工程心脏瓣膜的研究提供了新的策略和方向,具有广阔的应用前景。     

组织工程心脏瓣膜支架材料的选择与应用

背景：支架材料的选择在组织工程心脏瓣膜中起着至关重要的作用,支架材料的选择也就影响着组织工程心脏瓣膜的构建效果。 目的：评价组织工程心脏瓣膜支架材料的的优缺点,并对其选择进行总结。 方法：以 “组织工程,心脏瓣膜,支架材料,生物相容性”,为中文关键词;以:“tissue engineering,heart valves, scaffold material, biocompatibility” 为英文关键词,采用计算机检索1993-01/2009-10相关文章。纳入与有关生物材料与组织工程心脏瓣膜的相关的文章;排除重复研究及Meta分析类文章。 结果与结论：人工合成高分子材料有更大的可控性,可预先塑性,大量制备,孔径和孔隙率较容易控制,成本低廉;天然生物材料和合成高分子材料都存在一定不足,将人工可降解材料与天然材料相结合构建瓣膜支架,发挥两者各自的优势构建出性能良好的组织工程心脏瓣膜。组织工程心脏瓣膜的研究前景广阔。但距离临床应用还有很长的路要走,相信随着研究的不断深入以及支架材料的不断优化对组织工程心脏瓣膜构建方法的改进,在不远的将来造福于广大心脏瓣膜病患者。     

心脏生物起搏器的应用进展

背景：生物起搏器不需要更换电池,可接近磁场,对体内神经递质有自动反应性,有望成为临床治疗心脏传导系统疾病的一种有效方法。 目的：从基因治疗、细胞移植、激素治疗3方面总结生物起搏器的构建方法。 方法：以“生物起搏器”为检索词,应用计算机检索2000-03/2009-03万方数据库的相关文章,并限定文章语言种类为中文;同时计算机检索2000-03/2009-03 PubMed数据库相关文章,检索词为“biological pacemaker”,并限定文章语言种类为English。共检索到105篇文章,最终纳入符合标准的25篇文献进行综述。 结果与结论：目前,生物起搏器的构建主要有基因转导、细胞移植与激素治疗3种方法。生物“起搏器”的研究还处于动物实验研究阶段,将它应用于临床实践中还有很多问题需要研究和解决,如怎样获得高效、安全的基因转染载体,细胞移植的最佳部位,起搏功能的调控及免疫排斥反应的处理等。随着细胞生物学、细胞电生理学、分子生物学及基因工程技术的飞速发展,现阶段存在的问题会逐步得到解决,相信心脏生物起搏器将成为临床治疗心脏传导系统疾病的一种有效方法。     

骨髓间充质干细胞向内皮细胞的分化和临床应用

背景：目前国内外研究初步证明,骨髓间充质干细胞可以诱导分化为血管内皮细胞。 目的：综述骨髓间充质干细胞向内皮细胞的分化和临床研究进展。 方法：应用计算机检索2000/2011 PubMed数据库相关文章,检索词为“bone marrow mesenchymal stem cell,endothelial cell,differentiation,tissue engineered”,并限定文章语言种类为English。同时计算机检索2000/2011万方数据库相关文章,检索词为“骨髓间充质干细胞,内皮细胞,分化,临床应用”,并限定文章语言种类为中文。共检索到文献418篇,最终纳入符合标准的文献31篇。 结果与结论：骨髓间充质干细胞具有自我更新和多向分化潜能,在一定的诱导条件下可以向血管内皮细胞分化。血管内皮细胞是组织工程化血管的重要组成成分。利用骨髓间充质干细胞进行血管内皮构建,既可促进组织工程化器官的血管再生,又为组织工程化器官提供血供,同时也为临床治疗缺血性疾病奠定了基础。     

Application of tissue-engineering principles toward the development of a semilunar heart valve substitute

Heart valve disease is a significant medical problem worldwide. Current treatment for heart valve disease is heart valve replacement. State of the art replacement heart valves are less than ideal and are associated with significant complications. Using the basic principles of tissue engineering, promising alternatives to current replacement heart valves are being developed. Significant progress has been made in the development of a tissue-engineered semilunar heart valve substitute. Advancements include the development of different potential cell sources and cell-seeding techniques; advancements in matrix and scaffold development and in polymer chemistry fabrication; and the development of a variety of bioreactors, which are biomimetic devices used to modulate the development of tissue-engineered neotissue in vitro through the application of biochemical and biomechanical stimuli. This review addresses the need for a tissue-engineered alternative to the current heart valve replacement options. The basics of heart valve structure and function, heart valve disease, and currently available heart valve replacements are discussed. The last 10 years of investigation into a tissue-engineered heart valve as well as current developments are reviewed. Finally, the early clinical applications of cardiovascular tissue engineering are presented.     

Tissue-engineered heart valve leaflets: an animal study.

BACKGROUND: Tissue-engineered heart valve leaflets are a promising way to overcome the inherent limitations of current prosthetic valves. The aim of this study was to compare the biological responses of an autologous cell seeded scaffold and an acellular scaffold implanted in the pulmonary valve leaflet in the same animal. METHODS: Myofibroblasts and endothelial cells were isolated and cultured from an ovine artery. A synthetic biodegradable scaffold consisting of polyglycolic acid and polylactic acid was initially seeded with the myofibroblasts, then coated with endothelial cells. Cells were seeded using a medium containing collagen and cultured. A tissue-engineered construct and a plain scaffold were implanted as double pulmonary valve leaflet replacement in the same animal in an ovine model (n=3). Additionally, the tissue-engineered construct (n=2) and the plain scaffold (n=2) were implanted as single valve leaflet replacements for long-term analysis. After sacrifice, the implanted valve leaflet tissues were retrieved, analyzed visually and using light microscopy. RESULTS: Three animals that underwent replacement of two valve leaflets with a tissue-engineered construct and a plain scaffold, survived only a short-time (12, 24, 36 hours). The death was attributed to heart failure caused by severe pulmonary insufficiency. Animals that underwent single valve leaflet replacement survived longer and were electively sacrificed at 6 and 9 weeks after operation. The analysis of the leaflets from the short-term survivors showed that the tissue-engineered constructs contained less fibrins and protein exudates than the plain scaffold. In contrast, leaflets obtained from animals surviving 6 and 9 weeks showed similar well organized granulation tissues in the tissue-engineered constructs and the plain scaffolds. CONCLUSION: This animal experiment demonstrates that in the early phase of implantation, the tissue-engineered construct shows a better biological response in terms of antithrombogenicity than the plain scaffold, although both of them have similar results in the later reparative phase.     

利用人骨髓基质干细胞构建组织工程心脏瓣膜的体外实验

BACKGROUND:Nowadays, mechanical or biological valve recipients used in the clinic are still at the risk of infection, hemorrhage, thrombosis and reoperation owing to valve stenosis. Tissue-engineered heart valve with biological activity can overcome the disadvantages above. While, the optimal choice of scaffolds and seeding cells remains disputable. OBJECTIVE:To explore the feasibility to construct tissue-engineered heart valve with acellularized porcine aortic valve scaffold and human bone marrow stromal stem cells in vitro. METHODS:The porcine aortic valves were decellularized with the detergent and enzymatic extraction process to remove the cellular components. Human bone marrow stromal stem cells were aspirated from sternum of the patients with simple congenital heart malformation, and then the cells were seeded on the acellularized porcine aortic valve scaffold and cultured for 5 days. RESULTS AND CONCLUSION:Flow cytometry identified that the characteristics of surface antigen of the inoculated seed cells were in line with those of human bone marrow stromal stem cells. Light microscopy and electron microscopy confirmed that the cellular components in the porcine aortic valves could be removed to obtain the complete acellular fiber mesh stent. There was no significant difference in biomechanical property between before and after acellularization. The human bone marrow stromal stem cells implanted on the acellularized porcine aortic valve scaffold could form a continuous cell layer on the surfaces of the scaffold. The inoculated bone marrow stromal stem cells could be differentiated into fibroblasts. The implantation of human bone marrow stromal stem cells on the acellularized porcine aortic valve scaffold can construct the tissue-engineered heart valve.     

Bioreactors for Development of Tissue Engineered Heart Valves

Millions of people worldwide are diagnosed each year with valvular heart disease, resulting in hundreds of thousands of valve replacement operations. Prosthetic valve replacements are designed to correct narrowing or backflow through the valvular orifice. Although commonly used, these therapies have serious disadvantages including morbidity associated with long-term anticoagulation and limited durability necessitating repeat operations. The ideal substitute would be widely available and technically implantable for most cardiac surgeons, have normal hemodynamic performance, low risk for structural degeneration, thrombo-embolism and endocarditis, and growth potential for pediatric patients. Tissue engineered heart valves hold promise as a viable substitute to outperform existing valve replacements. An essential component to the development of tissue engineered heart valves is a bioreactor. It is inside the bioreactor that the scaffold and cells are gradually conditioned to the biochemical and mechanical environment of the valve to be replaced.     

Scaffolds for tissue engineering of cardiac valves

Tissue engineered heart valves offer a promising alternative for the replacement of diseased heart valves avoiding the limitations faced with currently available bioprosthetic and mechanical heart valves. In the paradigm of tissue engineering, a three-dimensional platform – the so-called scaffold – is essential for cell proliferation, growth and differentiation, as well as the ultimate generation of a functional tissue. A foundation for success in heart valve tissue engineering is a recapitulation of the complex design and diverse mechanical properties of a native valve. This article reviews technological details of the scaffolds that have been applied to date in heart valve tissue engineering research.     

组织工程心脏瓣膜细胞生物学研究进展

由于现有的机械瓣和生物瓣仍存在种种不足，如不具备生长性、需抗凝、易感染、不能生长和自我修复等。组织工程心脏瓣膜是一新兴的研究领域，涉及多门学科。构建组织工程心脏瓣膜应包括支架的制作、细胞的种植、瓣膜的体外培养和最终移植人人体。其中种植的细胞是组织工程心脏瓣膜的基本要素。就组织工程心脏瓣膜的细胞生物学研究进展做一综述。     

运动性关节软骨缺损支架材料的选择及其生物相容性

背景：骨软骨支架是用于承载细胞,供细胞黏附、生长、增殖、分化的载体。 目的：总结运动性关节软骨缺损支架材料的应用进展及其生物替代材料的生物相容性。 方法：以“关节软骨,生物材料,工程软骨,支架材料,生物相容性”为中文关键词,以“ tissue enginneering ,articular cartilage,scaffold material”为英文关键词,采用计算机检索维普数据库、PubMed数据库1993-01/2010-11相关文章。纳入与有关修复关节软骨损伤、生物材料、支架材料、生物相容性等相关的文章。以20篇文献为重点对运动性关节软骨缺损修复用的生物材料的生物相容性进行了讨论。 结果与结论：天然软骨支架材料因其具有细胞识别信号,故生物相容性好,细胞黏附率高,但力学性能较差。有些人工合成材料生物相容性不理想、亲水性差、对细胞吸附不足,人工合成高分子聚合物生物相容性良好。复合支架利用不同生物材料的优点克制材料的局限性制备理想的复合支架,其混合比例、混合技术还有待进一步研究。目前尚无一种材料完全满足组织工程的要,通过材料制备技术的改进或将几种不同材料的复合,材料的性能会不断的提高。     

Artificial aortic valves: an overview

This review discusses strategies that may address some of the limitations associated with replacing diseased or dysfunctional aortic valves with mechanical or tissue valves. These limitations range from structural failure and thromboembolic complications associated with mechanical valves to a limited durability and calcification with tissue valves. In pediatric patients there is an issue with the inability of substitutes to grow with the recipient. The emerging science of tissue engineering potentially provides an attractive alternative by creating viable tissue structures based on a resorbable scaffold. Morphometrically precise, biodegradable polymer scaffolds may be fabricated from data obtained from scans of natural valves by rapid prototyping technologies such as fused deposition modelling. The scaffold provides a mechanical profile until seeded cells produce their own extra cellular matrix. The microstructure of the forming tissue may be aligned into predetermined spatial orientations via fluid transduction in a bioreactor. Although there are many technical obstacles that must be overcome before tissue engineered heart valves are introduced into routine surgical practice these valves have the potential to overcome many of the shortcomings of current heart valve substitutes.