生物分子模板功能化纳米材料的研究进展

随着纳米科技的快速发展,纳米材料得到了广泛的应用,性质也得到了全面的发挥.科学家在对生物矿化分子进行充分研究的基础上,发现利用蛋白质、多肽、DNA、RNA、多糖等生物分子作为模板进行功能化无机纳米材料的设计和制备是一种有效和可行的方法.基于生物分子制备的纳米材料具有几何尺寸高度均一、结构多样、稳定性良好、制备过程环保等特性,因此近些年来成为研究的热点,同时合成出的材料具有很好的应用前景.本文主要对近年来利用生物分子为模板的纳米材料制备方法、材料实际应用以及所涉及的应用机理等方面的研究进行了综述.     

甲壳素及其衍生物壳聚糖的药理作用和临床应用研究进展

甲壳素及其衍生物壳聚糖是一种用途很广的天然高分子化合物,具有无毒、生物相容性好、吸附功能强、生物可降解等优异性能。随着对新材料的研究开发,甲壳素和壳聚糖在医药和卫生材料方面的研究成果已得到实际应用,甚至已工业化生产。综述了甲壳素和壳聚糖抗菌、止血、促愈合、提高免疫的药理作用及其在医用敷料方面的应用。     

聚赖氨酸的生物医学领域应用现状

聚赖氨酸是一种天然的阳离子聚酰胺聚合物,具有良好的生物相容性和生物可降解性,因而在生物医学应用中显示出巨大的潜力。聚赖氨酸侧链上众多的氨基基团为功能化提供了结合位点,可形成众多衍生物。聚赖氨酸的高分子材料具有阳离子特性、生物相容性、无毒性和刺激响应特性,在生物医学领域中得到实际应用。介绍了聚赖氨酸在递送系统、生物黏合剂和生物纤维等生物医学领域的应用,希望挖掘聚赖氨酸类材料在生物医学应用方面巨大的潜力。     

关节软骨组织工程支架材料研究进展

组织工程学是一门交叉学科,它利用工程学和生命科学的原理,来研究和发展具有生物活性的人工替代物.用以维持、恢复或提高人体受损组织的功能.目的是利用人体活细胞在适宜的支架材料上生长成天然的组织和器官以替代人体内受损和缺失的组织和器官.支架材料的选择是组织工程学研究的焦点之一.支架材料作为人工细胞外基质,为功能细胞的停泊、生长、繁殖、新陈代谢提供三维空间.理想的软骨组织工程支架应具有良好的生物组织相容性、良好的结构相容性、良好的表面活性、生物可降解性、可塑性和一定的机械强度.目前,关节软骨组织工程支架材料研究主要涉及天然材料、人工合成材料、人工和天然复合材料、纳米材料.本文就关节软骨组织工程支架材料进行综述.     

热活性聚合物在生物技术中的应用

热活性聚合物是具有独特性质的高分子材料，在生物技术中有可能得到广泛应用。术文简要介绍热活性聚合物在生物技术中的应用现状与发展趋势，并概述了热活性水凝胶及沉淀聚合物在亲和沉淀、固定化生物催化剂、浓缩生物大分子及免疫测定等生物技术中所显示的独特功能。     

“天然药物合成生物学”专栏——致辞

合成生物学是近十年来,在生物信息学、系统生物学等研究的基础上发展起来的一门工程生物科学,既包括对现有生物系统的改造和优化,也包括从头合成具有预定功能的全新人工生命系统。从2000年开始,合成生物学的发展进入了一个快速道,被广泛地应用到医药、化工、材料、能源、环境和农业等各个方面,取得了突飞猛进的发展。而天然药物合成生物     

基于透明质酸超分子特性对中药小分子化合物功能改进的研究进展

透明质酸由于其良好的生物相容性、可降解性、亲水性、肿瘤靶向性、黏性等特征广泛应用于生物材料、化妆品、临床医学等领域。中药小分子化合物具有显著的药效学活性,但仍存在溶解度低、靶向性差等缺点,这使其临床应用受到限制。基于透明质酸的超分子特性,本文汇总了国内外众多学者利用透明质酸作为载体对中药小分子化合物的溶解性、生物利用度、靶向性、适宜剂型等进行改善和功能提高的研究,将对挖掘中药小分子化合物潜在应用价值及新药研发提供新的思路和启发。     

骨科生物医学材料的临床应用

目的探讨骨科生物医学材料在临床中的应用。方法进行电子搜索,对于2004年～2013年在Web of Science 数据库上收录的骨科生物医学材料进行分类分析。结果在Web of Science 数据库上找到足够数量的骨科生物医学材料文献,这些文献表明,中国在该领域具有一定的研究地位。结论生物医学工程和生物材料工程的快速发展,使得医学材料得到广泛的应用。在骨科这一领域,生物医学材料的种类繁多,骨科生物医学材料按材料的性质分为金属材料、非金属材料、高分子材料和生物复合材料等,各种材料在机械强度、抗疲劳性、耐腐蚀性和生物安全性方面都具有各自的特点。     

肝细胞体外三维培养技术进展

改进肝细胞培养技术,实现大规模体外培养活力旺盛、功能稳定的肝细胞在生物型人工肝支持系统、肝细胞移植等方面具有广泛的用途。近年来,国内外在肝细胞三维组织化培养的研究方面取得了较大的进展,使体外肝细胞培养密度大大增加,肝细胞功能维持时间大大延长。本文就相关文献,对肝细胞体外组织化培养技术的研究进展进行综述。1胞外生物支架材料的应用研究者对各种胞外支架材料进行了研究,包括聚乙烯树脂、海藻酸盐、聚氨酯泡沫等,都是具有亲水多孔性结构的天然或人工合成的有机大分子。在一定的培养条件下,肝细胞在基质孔隙中重组形成许多有…     

生物黏附制剂研究的新进展

为系统了解生物粘附制剂的类型、性质,以及腔道给药新进展,对近期文献进行检索、分类和整理.结果发现,生物黏附制剂研究比较活跃.但性能优良的生物黏附材料的品种较少,生物黏附机制尚不完全清楚,生物黏附制剂的实验研究方法有待改善.生物黏附制剂具有较好的应用前景.     

Atelocollagen for protein and gene delivery

Recent progress in recombinant gene technology and cell culture technology has made it possible to use protein and polynucleotides as effective drugs. However, because of their short half-lives in the body and the necessity of delivering to target site, those substances do not always exhibit good potency as expected. Therefore, delivery systems of such drugs are important research subjects in the field of pharmacology, and to prolong the effect of these drugs, many studies are being conducted to control the release of proteins and polynucleotides from various carrier materials. Collagen is one of the most useful carrier materials for this purpose. In this article, we report on the controlled release of protein drugs using collagen, focusing on a new drug delivery system (DDS), the Minipellet, as our basic technology. Then we introduce our recent work about gene therapy using collagen-based DDS. Basic formulation study showed that collagen DDS protects DNA degradation from both chemical cleavage and enzymatic digestion. A single injection of collagen DDS containing plasmid DNA produced physiologically significant levels of gene-encoding proteins in the local site and systemic circulation of animals and resulted in prolonged biological effects. These results suggest that collagen DDS containing plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Also, variety kinds of application of collagen DDS for gene therapy using adenovirus vector, antisense DNA and DNA vaccine, will be discussed.     

缺氧/复氧诱导心肌细胞分泌高表达miR-208b的外泌体而调控心肌成纤维细胞活化、迁移和铁死亡

目的　探讨缺氧/复氧诱导心肌细胞所分泌的外泌体能否通过miR-208b调控心肌成纤维细胞的生物学功能。方法　心肌细胞进行缺氧/复氧处理后,收集所分泌外泌体与心肌成纤维细胞进行共培养,然后用荧光定量PCR、Western blot或酶联免疫吸附试验（ELISA）检测miR-208b、α-平滑肌肌动蛋白（α-SMA）、Collagen Ⅰ、Collagen Ⅲ和谷胱甘肽过氧化物酶4（GPX4）的表达,细胞计数试剂盒-8（CCK-8）检测细胞存活力,Transwell检测细胞迁移,商用试剂盒检测活性氧（ROS）、丙二醛（MDA）和Fe²⁺的累积。采用单因素方差分析（ANOVA）。结果　缺氧/复氧诱导心肌细胞和其分泌的外泌体高表达miR-208b,将此类外泌体加入到心肌成纤维细胞进行共培养时发现,心肌成纤维细胞可以摄入外泌体,从而上调自身miR-208b的表达,进而促进心肌成纤维细胞的存活力和迁移,增强α-SMA、Collagen Ⅰ和Collagen Ⅲ的表达,不过miR-208b的抑制物能显著减弱上述外泌体对心肌成纤维细胞生物学功能的调控作用。同时,缺氧/复氧心肌细胞源性外泌体能进一步增强铁死亡主要指标ROS、MDA和Fe²⁺的累积,抑制铁死亡关键调控因子GPX4的表达,不过miR-208b的抑制物能明显减弱Erastin和缺氧/复氧心肌细胞源性外泌体对铁死亡的影响作用。结论　缺氧/复氧心肌细胞源性外泌体能通过高表达的miR-208b而调控心肌成纤维细胞的生物学功能,表明miR-208b是介导心肌细胞和心肌成纤维细胞间通讯的关键分子。     

Clinical application of a human-collagen fleece as haemostatic agent

Local haemostatic agents have been employed for years in all surgical fields. Collagen has proved superior to other materials in terms of its haemostatic effect and good tolerability. A human-collagen fleece (Beristypt) is now available for the first time. A special manufacturing process excludes the possibility of human-pathogenic viruses being transmitted. The good clinical efficacy of human-collagen fleece for the indication haemostasis and the fact that it is easy to use, have been demonstrated in 63 operations in four surgical fields. Human-collagen fleece was well tolerated; no adverse effects were reported. The use of human-collagen fleece is a promising adjuvant method for improvement of surgical haemostasis.     

Berberine inhibits the interleukin-1 beta-induced inflammatory response via MAPK downregulation in rat articular chondrocytes

Osteoarthritis (OA) is one of the most chronic degenerative arthritic diseases, which gradually results in chondrocyte changes, articular cartilage degeneration, subchondral bone sclerosis, joint pain, swelling, and dysfunction. Berberine (BBR) has various confirmed biological activities, such as anti-inflammatory and antioxidant activities. However, the effect of BBR on the production of inflammation-associated proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, metalloproteinases (MMPs), Collagen II, TNF-α, and IL-6 via the MAPK (mitogen-activated protein kinases) pathway in IL-1β-stimulated rat chondrocytes, has not yet been studied. Thus, the purpose of this study was to evaluate whether BBR would decrease the production of inflammation-associated proteins through the MAPK signal pathway. Rat chondrocytes were cultured and pretreated with BBR at different concentrations (0, 25, 50, and 100 μM) and then stimulated with or without IL-1β (10 ng/mL). The mRNA expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 was measured by real-time polymerase chain reaction (RT-PCR), and the protein expression of iNOS, COX-2, Collagen II, MMP-3,MMP-13, and MAPKs were measured by Western blotting. The results showed that the expression of iNOS, COX-2, MMP-3, MMP-13, TNF-α, and IL-6 increased in the IL-1β-treated group and BBR showed an ability to inhibit the elevated expression under the pretreatment. Furthermore, the IL-1β-induced downregulation of Collagen II could be ameliorated by BBR. Moreover, the expression of MAPKs was significantly decreased by BBR. These results demonstrated that BBR had the anti-catabolic and anti-inflammation abilities that were through the MAPKs in IL-1β-induced rat chondrocytes. These findings may provide a novel therapeutic choice for treatment of OA using BBR.     

胶原蛋白在血管移植物中的应用研究进展

目的：全面探讨胶原蛋白在血管移植物中的作用,为血管移植物的研究及开发提供参考。方法： 通过PubMed数据库查阅国内外关于应用胶原蛋白进行血管移植物制备的相关研究文献,并对其进行整理、汇总。结果与结论：胶原蛋白是体内主要蛋白质之一,在血管壁的三层均有分布。它有利于血管内皮细胞生长及平滑肌细胞的附着,能维持血管壁的机械性能,与血管疾病的发生密切相关。胶原蛋白是具有良好的生物相容性、生物活性及可降解性的生物材料,可作为血管涂层、血管支架原材料或者与细胞联合应用以构建血管移植物并显示了良好的效果。在制备工艺方面,铸造和纺丝是目前大规模生产胶原蛋白血管移植物的主要方法,而3D打印等新的技术也在不断发展,并在血管移植物的制造中得到应用。随着制造、材料、医学技术的不断发展,胶原蛋白仍是未来用于制备血管移植物的理想原材料。     

骨移植替代用生物活性玻璃复合材料研究进展

生物活性玻璃作为生物材料的一种,以其良好的生物活性、生物相容性和良好的化学及机械性能在医药领域备受关注,将生物活性玻璃与其它材料进行复合,可获得优良的骨移植替代材料,具有广阔的应用前景,本文试图将生物活性玻璃复合材料的研究进展作一综述。     

Regulatory considerations for raw materials used in biological products

Raw materials are critical components of product manufacture; these include source materials such as cell substrates, tissues, and biological fluids required for product manufacture, as well as biological materials required for cell growth, propagation, differentiation, and selection. Adventitious viruses are a major safety concern in biological raw materials. This paper discusses the specific concerns related to different types of biological materials and presents the Center for Biologics Evaluation and Research's perspective on the qualification and management of raw materials for purposes of developing a safety program for the manufacture of biological products.     

重组胶原蛋白和明胶的研究进展

胶原蛋白和明胶被广泛用作生物高分子材料和医用材料,主要从动物皮、骨等组织中提取得到.由于传统提取方法制得的产品存在的固有缺陷,使其应用受限.利用化学合成法合成类胶原蛋白,以及运用基因工程技术,通过不同表达系统生产重组胶原蛋白和明胶,解决了传统提取方法存在的缺点,同时也改善了亲水性、免疫排异性等,并赋予其新的生物医学性能,成为近些年来的研究热点.本文对其研究进展进行综述.     

Modulation of collagen turnover in cardiovascular disease

Collagen fibers are the most abundant components of the extracellular matrix in arteries and myocardium. Disturbances in the collagen turnover (synthesis and degradation) have been linked to inflammatory diseases including cardiovascular pathological syndromes. In the myocardium, changes in collagen turnover may result in ventricle dilatation and subsequent contractile dysfunction. In arteries, collagen synthesis and degradation are associated with the progression of atherosclerotic disease and intimal hyperplasia following injury. Collagen synthesis is tightly regulated at several levels: synthesis of procollagens, suitable folding of polypeptides, secretion and cross-linking of mature fibers. On the other hand, degradation of newly synthesised procollagen and mature collagen fibers depends on the action of Matrix-Metalloproteinases (MMPs). The major role of collagen turnover in cardiovascular disorders has stimulated the search for pharmacological agents that interfere with collagen turnover at different levels. These drugs can theoretically act through modulation of the synthesis of procollagens or by interference with their post-translational modifications. Another group of pharmacological agents inhibit collagen breakdown (MMP inhibitors). Beneficial effects of compounds that target collagen metabolism have been reported. Unfortunately, many of these compounds also give rise to serious adverse effects due to interference with vital biological processes in which collagen plays an important role. In this paper, we will review cardiovascular diseases in which altered local collagen turnover is a key feature. Subsequently, the effect of compounds that have been developed and tested to modulate collagen synthesis, cross-linking or breakdown will be discussed.     

Global regulatory registration requirements for collagen-based combination products: points to consider

Collagen-based medical products provide an ideal and unique matrix for the delivery of drugs, biologics and other therapeutic agents. Collagen has a long history of safety and effectiveness. Collagen is biodegradable with minimal tissue reaction. Regulatory requirements for approval of collagen-based combination products are changing as more high technology combinations are developed. There are special considerations that need to be addressed for collagen products. Products of animal origin must meet specific requirements in regards to safety factors regarding Transmissable Spongiform Encephalopathies. Global regulatory registration requirements and special controls are presented.