聚乙烯醇及其复合材料在组织工程支架中的应用

背景：聚乙烯醇是具有良好生物相容性和生物降解特性的聚合物,因其水溶性、成膜性、乳化性、胶黏性,而且无味无毒,被广泛用于临床领域。目的：综述聚乙烯醇及其复合材料在骨、软骨、皮肤、血管等组织工程支架中的应用。方法：由第一作者检索2000年1月至2011年12月中国知网数据库、1980年1月至2012年12月Pubmed数据库及 Elsevier数据库中,有关聚乙烯醇及其复合材料在骨、软骨、皮肤、血管等组织工程支架中应用的文章,中文关键词为 “聚乙烯醇,复合材料,组织工程支架”,英文关键词为 “Poly (vinyl alcohol),composite material, tissue engineering scaffold”。结果与结论：虽然聚乙烯醇及其复合材料还存在强度不够高、植入后有并发症等缺点,但这类材料具有良好的生物相容性和生物可降解特性,在组织工程中的应用从实验室到临床前研究都有很大的进展。对于其修复的长期效果还需要进一步深入研究。通过对材料表面进行修饰,改善细胞与支架材料的相互作用;通过模拟细胞生长微环境,制备仿生材料,提高材料的亲水性、对细胞的黏附性,促进细胞的分化增殖;构建具有可控三维多孔结构的支架,并赋予其控制释放细胞生长因子等功能,更好地仿生天然细胞外基质的结构和功能;制备出降解速度与机械强度能够完全适应组织再生需要的支架,研制复合、仿生材料是今后支架材料研究的主要方向。     

明胶基生物材料在组织工程中的应用

本主要对明胶及其复合材料在组织工程领域的研究进展作了评述，表明明胶基生物材料作为种子细胞和信号分子的载体具有广阔的应用前景。     

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     

组织工程支架材料在脊髓损伤修复中的应用

背景：脊髓损伤最初往往会导致细胞和组织的不断丢失,组织工程支架可以模拟细胞外基质的生理状态,从而有利于细胞的黏附、迁移、扩增和分化。 目的：总结近年来组织工程支架材料联合细胞和/或细胞因子修复脊髓损伤的新进展。 方法：应用计算机检索PubMed、Ovid Medline及CBM数据库中2000-10/2010-10 与组织工程支架材料修复脊髓损伤相关的文章。  结果与结论：组织工程材料治疗脊髓损伤需要3 因素：种子细胞、组织工程支架、细胞因子。组织工程支架对于损伤脊髓断端起到桥接作用,而种植于材料的种子细胞和/或细胞因子可以促进神经轴突的生长和迁移。可用于组织工程支架的材料可分为天然材料和人工合成材料,包括胶原、壳聚糖、琼脂糖/藻酸盐、聚乳酸、纤连蛋白、聚羟基乙酸/聚乳酸、聚β羟丁酸等,动物实验已经取得一些成果,显示组织工程支架材料联合细胞移植修复效果更好,但临床上目前尚无开展组织工程支架材料修复脊髓损伤的研究。     

组织工程在病损组织替代中的应用

本文介绍了组织工程（ＴｉｓｓｕｅＥｎｇｉｎｅｅｒｉｎｇ）的国内外最新研究现状，主要就组织工程化组织在病损组织的替代以及细胞外基质替代物所用的生物材料、支架、种子细胞在基质上的培养研究情况作一综述，并对其面临的问题及开发应用提出了一些看法，供有关人员参考     

细胞外基质来源支架在软骨组织工程中的应用

BACKGROUND: At present, a variety of extracellular matrix-derived scaffolds have been successfully applied for cartilage tissue engineering in experiment and clinical practice. OBJECTIVE: To summarize the application and research status of extracellular matrix-derived scaffolds in cartilage tissue engineering. METHODS: A computer-based online search in PubMed, CNKI, CqVip and WanFang databases was performed using the keywords of “tissue engineering, cartilage, extracellular matrix, scaffolds” in English and Chinese, respectively. A total of 1 140 literatures were retrieved, and finally 65 eligible literatures were included. RESULTS AND CONCLUSION: In terms of the components, extracellular matrix-derived scaffolds are divided into monomeric natural polymers, mixed natural polymers, natural polymers compositing with synthetic polymers as well as acellular extracellular matrix-derived materials. Extracellular matrix-derived scaffolds hold good biocompatibility and degradability, and can promote proliferation and differentiation of choncrodytes; therefore, they as good bionic scaffolds have been applied for cartilage tissue engineering in clinical practice, However, poor mechanical properties and difficulty to molding should never be ignored. Further research should focus on improving the preparation technology by combining synthetic materials with extracellular matrix-derived scaffolds for cartilage tissue engineering.      

骨骼肌卫星细胞的培养及其在骨骼肌组织工程研究中的应用

近年来,随着组织工程技术的不断发展,生命科学、材料科学及制造科学的相互渗透,使得体外构建人体组织和器官的功能性替代物成为可能.骨骼肌卫星细胞作为组织工程的种子细胞在体外扩增至一定数量后与生物可降解三维支架材料结合,植入患者体内来修复缺损及恢复生理功能.目前对肌卫星细胞的体外培养已进行了较多研究,而对于肌卫星细胞的体外生长、增殖、鉴定,以及与组织工程三维支架的相互作用和生物功能的研究尚处于发展阶段,文中将对这些方面的研究进展作一综述.     

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.     

血管组织工程的研究及应用进展

血管组织工程是在体外构建理想的血管移植物，移植后无免疫排异反应，能维持血管腔长期通畅的一门新技术，本文综述了血管组织工程的定义，种子细胞的获取及生物相容性材料的选择，组织工程化血管的研究方法及当前进展，同时指出目前组织工程化血管研究存在的问题及对其未来的应用展望。     

组织工程在病损组织替代的应用

本文介绍了组织工程的国内外最新研究现状，主要就组织工程化组织在病损组织的替代以及细胞外基质替代物所用的生物材料、支架、种子细胞在基质上的培养研究情况作一综述，并对其面临的问题及开发应用提出了一些看法，供有关人员参考。     

Chitosan scaffolds containing hyaluronic acid for cartilage tissue engineering

Scaffolds derived from natural polysaccharides are very promising in tissue engineering applications and regenerative medicine, as they resemble glycosaminoglycans in the extracellular matrix (ECM). In this study, we have prepared freeze-dried composite scaffolds of chitosan (CHT) and hyaluronic acid (HA) in different weight ratios containing either no HA (control) or 1%, 5%, or 10% of HA. We hypothesized that HA could enhance structural and biological properties of CHT scaffolds. To test this hypothesis, physicochemical and biological properties of CHT/HA scaffolds were evaluated. Scanning electron microscopy micrographs, mechanical properties, swelling tests, enzymatic degradation, and Fourier transform infrared (FTIR) chemical maps were performed. To test the ability of the CHT/HA scaffolds to support chondrocyte adhesion and proliferation, live-dead and MTT assays were performed. Results showed that CHT/HA composite scaffolds are noncytotoxic and promote cell adhesion. ECM formation was further evaluated with safranin-O and alcian blue staining methods, and glycosaminoglycan and DNA quantifications were performed. The incorporation of HA enhanced cartilage ECM production. CHT/5HA had a better pore network configuration and exhibited enhanced ECM cartilage formation. On the basis of our results, we believe that CHT/HA composite matrixes have potential use in cartilage repair.     

Chitosan microchannel scaffolds for tendon tissue engineering characterized using optical coherence tomography

Tendon tissue engineering requires the generation of a uniaxially orientated collagen type I matrix with several organization scales that confer mechanical functionality upon the tendon. A combination of factors in a dose- and time-dependent manner, such as growth factors and mechanical environment, may be the key to an in vitro-engineered tendon. To define the progress of tissue development within a scaffold, on-line systems need to be applied to monitor the newly generated matrix. To address this challenge, we designed a new porous chitosan scaffold with microchannels (diameter: 250 microm), which allows primary porcine tenocytes to proliferate in a bundle-like structure. The cell proliferation and extracellular matrix (ECM) production within the microchannels were successfully assessed under sterile conditions using optical coherence tomography (OCT). A semi-quantitative method that calculated the microchannel occupation ratio (the degree of cell proliferation and tissue turnover based on the total backscattered intensity in the microchannels) was developed. We further investigated the effect of different culture conditions on tendon cell matrix formation. Using a perfusion bioreactor, we demonstrated how fluid flow can increase (p < 1e(3)) ECM production within the microchannels significantly more than static culture. Our study illustrates how using a guiding scaffold in combination with the fast and non-destructive assessment of the microstructure using OCT allows discrimination between the parameters affecting the production and the organization of the ECM.     

Chitosan/polyester-based scaffolds for cartilage tissue engineering: Assessment of extracellular matrix formation

Naturally derived polymers have been extensively used in scaffold production for cartilage tissue engineering. The present work aims to evaluate and characterize extracellular matrix (ECM) formation in two types of chitosan-based scaffolds, using bovine articular chondrocytes (BACs). The influence of these scaffolds’ porosity, as well as pore size and geometry, on the formation of cartilagineous tissue was studied. The effect of stirred conditions on ECM formation was also assessed. Chitosan-poly(butylene succinate) (CPBS) scaffolds were produced by compression moulding and salt leaching, using a blend of 50% of each material. Different porosities and pore size structures were obtained. BACs were seeded onto CPBS scaffolds using spinner flasks. Constructs were then transferred to the incubator, where half were cultured under stirred conditions, and the other half under static conditions for 4 weeks. Constructs were characterized by scanning electron microscopy, histology procedures, immunolocalization of collagen type I and collagen type II, and dimethylmethylene blue assay for glycosaminoglycan (GAG) quantification. Both materials showed good affinity for cell attachment. Cells colonized the entire scaffolds and were able to produce ECM. Large pores with random geometry improved proteoglycans and collagen type II production. However, that structure has the opposite effect on GAG production. Stirred culture conditions indicate enhancement of GAG production in both types of scaffold.     

Bilayered scaffolds for osteochondral tissue engineering

Osteoarthritis (OA) is a prevalent degenerative joint disease that places a significant burden on the socioeconomic efficacy of communities around the world. Tissue engineering repair of articular cartilage in synovial joints represents a potential OA treatment strategy superior to current surgical techniques. In particular, osteochondral tissue engineering, which promotes the simultaneous regeneration of articular cartilage and underlining subchondral bone, may be a clinically relevant approach toward impeding OA progression. The unique and complex functional demands of the two contrasting tissues that comprise osteochondral tissue require the use of bilayered scaffolds to promote individual growth of both on a single integrated implant. This paper reviews the three current bilayered scaffold strategies applied to solve this challenging problem, with a focus on the need for an innovative approach to design and fabrication of new optimized scaffold combinations to reinforce materials science as an important element of osteochondral tissue engineering.     

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     

牙髓牙本质组织工程生物支架材料的研究进展

背景：组织工程方法中选择合适的支架是关键性的步骤。 目的：回顾分析牙髓牙本质组织工程中支架材料的应用研究。 方法：由第一作者检索1993至2012年 PubMed数据及万方数据库有关牙髓牙本质组织工程中支架材料应用研究等方面的文献。 结果与结论：在牙髓牙本质组织工程中有包括天然生物、人工合成材料和复合材料在内的大量生物材料可供选择,每一种材料都有各自的生物学特点。其中胶原、聚酯、羟基磷灰石等是研究较多的支架材料。自组装多肽水凝胶是由氨基酸制成的新型支架材料,满足理想牙髓牙本质组织工程支架材料的大部分要求,是一种前景广阔的牙髓牙本质组织工程支架材料。     

Chitosan/gelatin porous scaffolds containing hyaluronic acid and heparan sulfate for neural tissue engineering

The novel chitosan (Cs)/gelatin (Gel) porous scaffolds containing hyaluronic acid (HA) and heparan sulfate (HS) were fabricated via freeze-drying technique, and their physicochemical characteristics including pore size, porosity, water absorption, and in vitro degradation and biocompatibility were investigated. It was demonstrated that the Cs/Gel/HA/HS composite scaffolds had highly homogeneous and interconnected pores with porosity above 96% and average pore size ranging from 90 to 140?μm and a controllable degradation rate. The scanning electron microscopic images, cell viability assay, and fluorescence microscopy observation revealed that the presence of HA and HS in the scaffolds significantly promoted initial neural stem and progenitor cells (NS/PCs) adhesion and supported long-time growth in three-dimensional environment. Moreover, NS/PCs also maintained mutilineage differentiation potentials with enhanced neuronal differentiation upon induction in the Cs/Gel/HA/HS composite scaffolds in relation to Cs/Gel scaffolds. These results indicated that the Cs/Gel/HA/HS composite scaffolds were suitable for neural cells’ adhesion, survival, and growth and could offer new and important options for neural tissue engineering applications.     

Chitosan tissue scaffolds by emulsion templating

A novel method for producing porous chitosan gels with controllable pore size and volume fraction has been developed. Complex-shaped 3D objects can be fabricated. Chitosan gels produced with the method are believed to be suitable candidates for tissue scaffolds. The method involves creating an oil-in-water emulsion in which the water phase contains chitosan and a temperature-activated cross-linking agent. The emulsion can then be poured or injected into a mould with the shape of the desired object. The chitosan is cross-linked by heating the emulsion to about 75 degrees C for about 15 min. The gelled object is then washed to remove the oil phase and surfactant. The gels were then dried in air, and further washed in ethanol. Scanning electron microscopy was then used to observe the pore size and fraction. The amount of porosity is directly proportional to the amount of oil phase. The pore size is controlled by the size of the oil droplets which is controlled primarily by the amount of surfactant added.     

Chitosan tissue scaffolds by emulsion templating

A novel method for producing porous chitosan gels with controllable pore size and volume fraction has been developed. Complex-shaped 3D objects can be fabricated. Chitosan gels produced with the method are believed to be suitable candidates for tissue scaffolds. The method involves creating an oil-in-water emulsion in which the water phase contains chitosan and a temperature-activated cross-linking agent. The emulsion can then be poured or injected into a mould with the shape of the desired object. The chitosan is cross-linked by heating the emulsion to about 75°C for about 15 min. The gelled object is then washed to remove the oil phase and surfactant. The gels were then dried in air, and further washed in ethanol. Scanning electron microscopy was then used to observe the pore size and fraction. The amount of porosity is directly proportional to the amount of oil phase. The pore size is controlled by the size of the oil droplets which is controlled primarily by the amount of surfactant added.     

Autologous extracellular matrix scaffolds for tissue engineering

Development of autologous scaffolds has been highly desired for implantation without eliciting adverse inflammatory and immune responses. However, it has been difficult to obtain autologous scaffolds by tissue decellularization because of the restricted availability of autologous donor tissues from a patient. Here we report a method to prepare autologous extracellular matrix (aECM) scaffolds by combining culture of autologous cells in a three-dimensional template, decellularization, and template removal. The aECM scaffolds showed excellent biocompatibility when implanted. We anticipate that "Full Autologous Tissue Engineering" can be realized to minimize undesirable host tissue responses by culturing the patient's own cells in an aECM scaffold.