关节软骨组织工程支架材料的研究进展

关节软骨缺损是临床上常见的一种关节病损,由于关节内机械力的影响以及血液供应的缺乏,软骨自身修复能力有限,对于其组织重建和功能恢复的探讨一直是最具有挑战性的课题之一.组织工程学作为一门新兴的学科,其应用生命科学和工程学再生软骨的原理和方法,为解决这一问题提供了新的思路,其中对于支架材料的研究开发在关节软骨组织工程修复中占有重要的地位.将支架材料分为天然生物材料和人工合成材料两大类进行重点阐述,并从支架材料的作用、要求以及空间结构等方面介绍了当前研究比较集中的几类支架的优缺点和发展状况.     

组织工程软骨支架材料的应用选择

背景：软骨损伤后几乎不可能完全修复,近年来采用组织工程学方法构建软骨复合组织已成为软骨修复方面新的研究领域。其中支架材料在软骨修复过程中起着至关重要的作用,支架材料的选择也就影响着整个修复过程。 目的：全面了解组织工程软骨支架材料的优缺点,并对其选择进行综述。 方法：由第一作者于2010-11在CBM、PubMed数据库(http://www.ncbi.nlm.nih.gov/PubMed)、万方数据库(http://www. wanfangdata.com.cn)及google学术网检索组织工程软骨支架材料方面的内容,检索时限为1990/2010,英文检索词为“cartilage, tissue engineering, scaffold materials, bone mesenchymal stem cell”,中文检索词为“软骨,组织工程,支架材料,骨髓间充质干细胞”,排除重复性研究。 结果与结论：计算机初检得到1 185篇文献,阅读标题和摘要进行初筛,排除因研究目的与本文无关及内容重复的研究1 142篇,共保留其中的43篇进行归纳总结,最终引入文献29篇。结果提示,目前应用于组织工程的支架不论是天然的还是人工合成的,都存在一定的缺陷,如体内降解速度过快或过慢,生物相容性不佳、引起炎症等问题。最重要的是组织工程软骨支架距临床应用仍有很大差距,而未来组织工程支架材料的研究重点是改进现有材料和制备工艺,研制复合材料、仿生材料、纳米材料及改性天然材料等。     

工程软骨支架的临床应用研究进展

移植工程软骨修复软骨损伤是目前较为理想的治疗方法,构建工程软骨需要种子细胞和支架材料,支架材料的性能对工程软骨的生物特性有重要影响.讨论支架材料的研究进展,比较不同支架材料的工程软骨的临床应用结果,对进一步改善工程软骨的生物学性能有重要意义.结合近年来工程软骨支架的研究和临床应用情况作一综述和展望.     

壳聚糖在软骨组织工程的应用

软骨组织工程的出现，为解决软骨修复这个临床难题提供了新的方案，然而目前软骨组织工程的热点在于寻找一种合适的生物载体材料。壳聚糖（chitosan)，一种人工合成的多聚糖材料，具有良好的生物相容性，可降解性和生物活性，可作为细胞三维生长支架，维持种子细胞新陈代谢和生长表型。本将就壳聚糖的理化特性，生物活性和在软骨组织工程方面应用的状况及前景作一综述。     

制备软骨组织工程支架的方法

背景：软骨组织工程支架作为软骨细胞外基质的替代物,其外形和孔结构对实现其作用和功能具有非常重要的意义。 目的：回顾目前若干种常用软骨组织工程中三维多孔支架的制备方法。 方法：由第一作者检索2000至2013年PubMed数据库,ELSEVIER SCIENCEDIRECT、万方数据库、中国知网数据库。英文检索词为“Cartilage tissue engineering;scaffolds;fabrication”,中文检索词为“软骨组织工程;制备方法;支架材料;多孔支架”。 结果与结论：制备软骨组织工程支架的方法有相分离/冷冻干燥法、水凝胶技术、快速成型技术、静电纺丝法、溶剂浇铸/粒子沥滤法及气体发泡法等。目前研究发现,支架中孔径的大小对组织的重建有着直接的影响,孔径为100-250 μm的孔有益于骨及软骨组织的再生。通过溶液浇铸/粒子沥滤法、气体发泡法所制备的支架孔径大小在这一范围内,因此比较适合用于骨、软骨组织工程支架的构建。研究人员通常将多种方法结合起来,以期能制备出生物和力学性能方面更加仿生的组织工程多孔支架。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：     

组织工程及其支架研究进展和面临的问题及展望

组织工程学是应用生命科学和工程学的原理和方法 ,去认识生物正常和病态组织结构 功能关系 ,设计、构造、改良、培育和培养活组织 ,研制生物替代物以修复或重建器官的结构 ,维持或改善组织器官功能的一门新兴边缘学科 ,是一个综合细胞生物学、材料科学、生物化学、化学工程、生物医学工程学和移植学等学科的交叉领域。组织工程学是 80年代末期才由美国兴起并发展起来的一门科学 ,其研究为利用遗传工程制备“真正的”仿生材料和人造器官开辟了光明的前景。可以认为 ,2 0世纪人工器官的出现已成为现代医学进步的一大标志 ,但因这些器官尚不具…     

脂肪干细胞在骨软骨组织工程中的研究进展

近年来,随着医学相关学科的迅猛发展,组织工程技术已经取得了很大的成就,但种子细胞一直是困扰人们的焦点问题.脂肪干细胞(ADSCs)体外扩增迅速,稳定性好,无免疫排斥反应,具有多向分化潜能,可以向脂肪细胞、成骨细胞、成软骨细胞、内皮细胞、肌细胞和神经细胞等不同胚层来源的细胞分化,并且脂肪组织具有取材方便、对人体创伤小、可大量获得等优点,因而ADSCs有望成为一种理想的组织工程种子细胞.旨在介绍ADSCs在骨软骨组织工程中的研究进展.     

关节软骨组织工程的研究进展

介绍了关节软骨组织工程中种子细胞、支架材料的研究现状以及生长因子在关节软骨组织工程中的应用进展，阐明了随着对细胞行为、支架材料特性、细胞与材料的组合构建研究的深入，组织工程在关节软骨修复方面应用前景十分广阔。     

软骨组织工程的研究现状及展望

目前,软骨组织工程的研究内容主要集中在以下几个方面:种子细胞;三维生物材料载体;细胞培养体系;人工软骨性能、实验动物模型和临床试验评价。我们综述了软骨组织工程的研究现状及其进展。     

多层软骨组织工程支架的制备

软骨组织工程为关节软骨损伤的治疗提供了一种理想的治疗途径,但体外构建的软骨如何在临床应用时采用适当的方法短期内在体内进行良好地固定仍然没有得到很好的解决,阻碍了采用组织工程方法治疗关节软骨疾病的临床应用.本研究通过冷冻干燥的方法制备出一个上层为胶原,下层逐层过渡到以羟基磷灰石为主的复合一体化软骨组织工程支架,利用复合支架下层羟基磷灰石良好的骨传导作用,将支架整体通过底部的快速固定达到对上层软骨进行固定的目的.本研究对该复合支架的制备及其形态结构特点进行了初步研究.结果表明胶原层的孔径孔隙率可以通过冷冻温度及胶原溶液浓度进行控制;羟基磷灰石粒度及其粒度分布明显影响其在胶原支架内部的分布;SEM照片表明用该方法制备出了三层具有不同羟基磷灰石含量的复合胶原羟基磷灰石软骨组织工程支架,支架总高度为6cm,每层高度约为2cm,三层之间不存在界面形成了一个均匀的整体结构.为软骨组织工程提供了一种新型的支架.     

聚乙烯醇-壳聚糖-胶原组织工程支架的研究

目的 以聚乙烯醇（PVA）、壳聚糖（Cs）和胶原（Col）为主要原料制备PVA-Cs—Col复合支架,并研究其作为组织工程支架材料的可行性。方法 把聚乙烯醇、壳聚糖和胶原按一定配比复合,测定复合材料的含水率、膨胀率和力学性能,扫描电镜观察材料横截面的组织形态。结果 不同分子量PVA与不同质量的cs和Col复合,得到的复合支架材料湿态抗张强度为5．70MPa,含水率在60．15％-72．50％,膨胀率在185．33％～317．57％。不同配比的复合支架具有不同的内部组织形态结构。结论 PVA—Cs—Col复合支架材料具有较高的含水率和适宜的膨胀率,内部孔洞丰富,Cs：PVA：Col的质量比为30：15：0．20时,复合支架综合性能较佳,适合用于组织工程支架材料。     

Biodegradable porous scaffolds for tissue engineering

 Three-dimensional scaffolds play an important role in tissue engineering as an adhesive substrate for implanted cells and a physical support to guide the formation of new organs. The scaffolds should facilitate cell adhesion, promote cell growth, allow the retention of differentiated cell functions, and be biocompatible, biodegradable, highly porous with a large surface-to-volume ratio, mechanically strong, and malleable. A number of biodegradable three-dimensional scaffolds have been developed for tissue engineering. This paper reviews some of the recent events in the development of these scaffolds. Received: March 6, 2002     

Microporous calcium phosphate ceramics as tissue engineering scaffolds for the repair of osteochondral defects: Histological results

Treatment of defects in joint cartilage aims to re-establish normal joint function. In vitro experiments have shown that the application of synthetic scaffolds is a promising alternative to existing therapeutic options. A sheep study was conducted to test the suitability of microporous pure β-tricalcium phosphate (TCP) ceramics as tissue engineering scaffolds for the repair of osteochondral defects. Cylindrical plugs of microporous β-TCP (diameter: 7 mm; length: 25 mm; porosity: 43.5 ± 2.4%; pore diameter: ～5 μm) with interconnecting pores were used. Scaffolds were seeded with autologous chondrocytes in vitro and cultured for 4 weeks. A drill hole (diameter 7 mm) was placed in both medial femoral condyles of sheep. For the left knee the defect was filled with a TCP plug and for the right knee the defect was left empty. After 6, 12, 26 and 52 weeks, seven animals from each group were killed and studied. The samples were examined employing histological, histomorphometric and immunohistological methods as well as various imaging techniques (X-ray, microcomputer tomography and scanning electron microscopy). After explantation the cartilage defects were first assessed macroscopically. There were no signs of infection or inflammation. Histological grading scales were used for assessment of bony integration and cartilage repair. An increasing degradation (81% after 52 weeks) of the ceramic with concomitant bone formation was observed. The original structure of cancellous bone was almost completely restored. After 26 and 52 weeks, collagen II-positive hyaline cartilage was detected in several samples. New subchondral bone had formed. The formation of cartilage began at the outer edge and proceeded to the middle. According to the O’Driscoll score, values corresponding to healthy cartilage were not reached after 1 year. Integration of the newly formed cartilage tissue into the surrounding native cartilage was found. The formation of biomechanical stable cartilage began at the edge and progressed towards the centre of the defect. After 1 year this process was still not completed. Microporous β-TCP scaffolds seeded with chondrocytes are suitable for the treatment of osteochondral defects.     

Effect of sterilization on structural and material properties of 3-D silk fibroin scaffolds

The development of porous scaffolds for tissue engineering applications requires the careful choice of properties, as these influence cell adhesion, proliferation and differentiation. Sterilization of scaffolds is a prerequisite for in vitro culture as well as for subsequent in vivo implantation. The variety of methods used to provide sterility is as diverse as the possible effects they can have on the structural and material properties of the three-dimensional (3-D) porous structure, especially in polymeric or proteinous scaffold materials. Silk fibroin (SF) has previously been demonstrated to offer exceptional benefits over conventional synthetic and natural biomaterials in generating scaffolds for tissue replacements. This study sought to determine the effect of sterilization methods, such as autoclaving, heat-, ethylene oxide-, ethanol- or antibiotic–antimycotic treatment, on porous 3-D SF scaffolds. In terms of scaffold morphology, topography, crystallinity and short-term cell viability, the different sterilization methods showed only few effects. Nevertheless, mechanical properties were significantly decreased by a factor of two by all methods except for dry autoclaving, which seemed not to affect mechanical properties compared to the native control group. These data suggest that SF scaffolds are in general highly resistant to various sterilization treatments. Nevertheless, care should be taken if initial mechanical properties are of interest.     

组织工程椎间盘支架材料的研究进展

椎间盘退行性病变引起的颈肩腰腿痛是临床最常见的疾病之一,而目前无论是手术或是非手术治疗的中远期疗效均存在一定的不足。近年来随着对椎间盘组织工程学技术的研究不断深入,椎间盘退行性病变的治疗也有了新的方向。而在椎间盘组织工程学中,如何构建适合搭载种子细胞的支架材料是目前的热点和难点之一。本文就椎间盘组织工程学中胶原蛋白、藻酸盐、壳聚糖及脂肪族聚酯均聚物等代表性支架材料研究中的进做一简要综述。     

Fabrication of large perfusable macroporous cell-laden hydrogel scaffolds using microbial transglutaminase

In this study, we developed a method to fabricate large, perfusable, macroporous, cell-laden hydrogels. This method is suitable for efficient cell seeding, and can maintain sufficient oxygen delivery and mass transfer. We first loaded three types of testing cells (including NIH 3T3, ADSC and Huh7) into gelatin hydrogel filaments, then cross-linked the cell-laden gelatin hydrogel filaments using microbial transglutaminase (mTGase). In situ cross-linking by mTGase was found to be non-cytotoxic and prevented the scattering of the cells after delivery. The gelatin hydrogel constructs kept the carried cells viable; also, the porosity and permeability were adequate for a perfusion system. Cell proliferation was better under perfusion culture than under static culture. When human umbilical vein endothelial cells were seeded into the constructs, we demonstrated that they stably formed an even coverage on the surface of the hydrogel filaments, serving as a preliminary microvasculature network. We concluded that this method provides a viable solution for cell seeding, oxygen delivery, and mass transfer in large three-dimensional (3-D) tissue engineering. Furthermore, it has the potential for being a workhorse in studies involving 3-D cell cultures and tissue engineering.     

Ligament tissue engineering: an evolutionary materials science approach

The anterior cruciate ligament (ACL) is important for knee stabilization. Unfortunately, it is also the most commonly injured intra-articular ligament. Due to poor vascularization, the ACL has inferior healing capability and is usually replaced after significant damage has occurred. Currently available replacements have a host of limitations, this has prompted the search for tissue-engineered solutions for ACL repair. Presently investigated scaffolds range from twisted fiber architectures composed of silk fibers to complex three-dimensional braided structures composed of poly (l-lactic acid) fibers. The purpose of these tissue-engineered constructs is to apply approaches such as the use of porous scaffolds, use of cells, and the application of growth factors to promote ligament tissue regeneration while providing mechanical properties similar to natural ligament.     

丝生物材料处理及其在组织工程中应用研究现状

丝纤维是一种天然的共聚物,其作为手术缝线等已在临床上应用多年.丝纤维由位于中间的丝素蛋白和包裹丝素蛋白的丝胶蛋白构成.近年来,丝纤维材料由于生物相容性良好,降解缓慢,而且具有非常优异的机械性能,因而其可以作为一种新的生物医学支架材料获得广泛应用.而且由于技术手段的发展,能够对丝纤维材料进行多种加工和处理将其加工成多种形态的支架材料和进行表面修饰,并且通过遗传工程和基因工程进行裁切和生产重组的丝蛋白类似物,这使其在生物医学工程领域有广阔的应用前景.     

静电纺丝技术构建组织工程气管支架的研究进展

支架的选择是组织工程气管替代研究的核心内容之一.阐述了电纺技术的概况及新发展,分析比较天然、合成和复合材料的电纺支架的优缺点,其在气管支架的选材及制作处理方法上的独特优势.对于具体实验或临床对象,应选择合适的聚合物,改进表面修饰技术及调控电纺纤维的结构尺寸和配置,以符合组织特异性和多样性,更好地构建组织工程气管支架.