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。     

生物降解材料复合成骨因子在骨科应用研究中的进展

背景：生物可降解植入物不仅可重建骨缺损部位,而且随着材料的逐步降解,新生骨组织可完全替代移植材料,填充骨缺损处。目的：总结生物降解材料复合成骨因子在骨科的研究进展。方法：以“可降解材料,成骨因子,细胞活性因子,骨组织工程;Biodegradable materials,factors,cell active factor,bone tissue engineering”为检索词,应用计算机检索PubMed、万方、CNKI数据库2000至2015年的相关文献。结果与结论：生物可降解医用高分子材料可分为天然高分子材料和人工合成可降解材料。天然高分子材料具有良好的生物相容性,但其机械强度较差;人工合成可降解材料械强度较天然高分子材料高,但容易造成局部酸性物质堆积,产生局部炎症反应。将生物可降解医用高分子材料与成骨因子复合,可提高材料的力学强度与骨诱导能力,但将其作为骨修复材料应用于临床还有很多问题需要解决。  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     

药物缓释载体材料在医药领域中的研究及应用

背景：药物缓释就是将小分子药物与高分子载体以物理或化学方法结合,在体内通过扩散、渗透等控制方式,将小分子药物以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的。 目的：总结药物缓释载体材料特征及其在医药领域中的应用。 方法：以“药物缓释、载体材料、生物降解、壳聚糖、聚乳酸、海藻酸钠”为中文关键词,以“Drug delivery,carrier material,biodegradable,chitosan,polylactic acid, sodium alginate”为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库(1993-01/2010-11)相关文章。纳入高分子生物材料-药物缓释载体等相关的文章,排除重复研究或Meta分析类文章,共入选31篇文章进入结果分析。 结果与结论：壳聚糖和聚乳酸是当前在药物缓释体系中应用较多的材料,它是将小分子药物与高分子载体以物理或化学方法结合, 以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的,较单一生物材料具有显著优越性,具有更好的生物相容性和生物可降解性。目前很多研究仍处于实验阶段,还有一些问题有待于解决,如制剂质量方法不成熟,剂量较难控制,成本较高等。     

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     

新型组织工程血管材料：静电纺复合纳米纤维小口径管状支架

背景：小口径人工血管对生物相容性和抗凝血的要求远远高于普通大口径人工血管,因此血管移植体内原位诱导组织再生成为了新的研究方向。 目的：总结近几年静电纺复合纳米纤维小口径管状支架的主要研究进展,并讨论其在体内原位诱导血管再生方面的重要应用。 方法：由第一作者检索中国期刊网CNKI全文数据库、万方数据库及ISI Web of Knowledge外文数据库,有关复合纳米纤维小口径管状支架的制备方法、血管支架仿生天然细胞外基质微环境的表面修饰以及种植体植入后生物相容性和安全性评价等方面的文献。 结果与结论：静电纺复合纳米纤维制备小口径管状支架,即将天然材料和合成材料共纺在一起,这样既能克服天然生物高分子材料力学性能的不足,又能避免合成材料在生物相容性和安全性的缺陷,成为制备小口径血管组织工程支架的必然趋势。同时制备多层血管,进行功能化修饰,模拟天然细胞外基质的结构和功能,将成为用于心血管组织修复及再生小口径血管组织工程研究的新方向。在获得上述新进展的同时,经动物实验检验的静电纺血管支架以聚合物为主。尽管这类支架采用了各种手段避免血栓、炎症等不良反应,其生物相容性仍旧无法与天然材料相比。由此可见,在天然材料与合成材料之间找到一个最佳比例,使复合材料的力学性能和血管相容性达到一个平衡,将会显著提高静电纺复合纳米纤维支架在小口径血管组织再生中的应用。     

软骨组织工程中支架材料的文献回顾*

背景：目前报道的软骨组织工程支架材料,大体分为天然高分子材料、人工合成可降解材料、天然材料与合成高分子材料复合构造的新型生物材料和纳米材料4大类。 目的：总结近年来国内外关于组织工程支架材料的文献,对其进行简要综述,并探讨目前存在的问题和应用前景。 方法：由第一作者应用计算机检索PubMed数据库及中国期刊网全文数据库1997-01/2011-01有关软骨组织工程支架材料的文章,英文检索词为“natural polymer materials,synthetic materials,new biological materials,nanometer materials,scaffold materials,cartilage tissue engineering”,中文检索词为“天然高分子材料,人工合成材料,新型生物材料,纳米材料,支架材料,软骨组织工程”。排除重复性研究,共保留33篇文献进行综述。 结果与结论：软骨组织工程支架已由先前的单一材料逐渐向复合材料转变,其孔隙率更高、抗原性更低、组织相容性更好,软骨细胞的黏附及增殖更好。结合计算机辅助设计和三维打印快速成形技术,将生物可降解材料预制加工成精确形状,通过降解速率较慢的内支撑支架,维持材料支架的精确外形,研发具有一定机械强度、适当孔径和精确外观形状的可降解生物支架材料是未来的发展方向。     

含糖聚合物在生物医药领域的应用

介绍了含糖聚合物的制备合成进展，综述了近年来含糖聚合物在医药材料、生物材料等领域中的应用，重点介绍了在高分子药物、高分子载体材料、生物材料，分离提纯材料等方面的应用，展望了含糖聚合物的新应用。     

含糖聚合物在生物医药领域的应用

介绍了含糖聚合物的制备合成进展 ,综述了近年来含糖聚合物在医药材料、生物材料等领域中的应用 ,重点介绍了在高分子药物、高分子载体材料、生物材料 ,分离提纯材料等方面的应用 ,展望了含糖聚合物的新应用     

蛋白多肽类药物口服纳米给药：现状、问题与前景

背景：研发药物新剂型和制剂新技术已成为有望提高蛋白多肽利用率的热点,尤其是近几年的纳米技术的研究进展更是促进了蛋白质药物的临床应用。 目的：综述蛋白口服纳米给药的研究现状。 方法：应用计算机检索CNKI数据库、SCI数据库1996至2014年文献,检索中英文关键词为“蛋白多肽,纳米粒,口服制剂;protein,peptide drugs,nanoparticles,oral administration”。 结果与结论：纳米材料种类、纳米粒粒径、表面电荷及其表面修饰等对药物的包封率、释药速度、纳米粒在胃肠道内的稳定性及透过肠黏膜的能力等方面有很大影响。纳米粒可增加蛋白药物的稳定性,提高药物的生物利用度;纳米粒的靶向性可减少某些药物的不良反应;纳米粒的缓释作用可以减少药物的用量,增加药物的体内循环时间。但纳米技术目前仍有很多问题有待解决：制备过程中不可避免地会使一些蛋白药物丧失活性;药物的包封率及载药量有待提高;蛋白突释问题不能完全解决;纳米粒目前大规模生产还很困难等。  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     

不同类型生物材料的心脏瓣膜应用及安全性评价

背景:组织工程心脏瓣膜是应用工程学和生命科学的原理和方法构建具有生理功能和生物活性的瓣膜替代物,但仍处于动物实验阶段。 目的：总结常用的组织工程心脏瓣膜,对不同类型生物材料的心脏瓣膜应用的安全性进行评价。 方法：以“生物材料,心脏瓣膜,支架材料,综述文献,组织工程”为中文关键词,采用计算机检索2000-01/2010-12相关文章。纳入与生物材料与组织工程心脏瓣膜研究相关的文章;排除重复研究或Meta分析类文章。 结果与结论：共纳入生物材料与组织工程心脏瓣膜研究相关文献20篇。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。     

抗菌生物材料的抗细菌黏附能力

背景：由于生物材料和人工器官在临床应用逐渐增多,给临床患者进行治疗疾病的同时还存在着一些问题,最为常见的是生物材料植入人体后引起的细菌感染。 目的：探讨生物材料在抗细菌黏附中的作用,抗菌生物材料的分类及特点。 方法：生物材料在机体引起各种感染的原因是由于细菌生物膜的形成,防止生物材料置入后感染的关键是抑制细菌在生物材料表面的黏附以及防止细菌在生物材料表面形成细菌生物膜。细菌表面黏附重点是改变细菌自身的特性和材料表面的物理化学性质,通过改变材料的物理化学性质来减小材料和细菌之间的相互作用力,主要采用化学接枝法、等离子体法、气相沉淀法等。预防细菌黏附首先要增强机体的免疫防御能力,其次要使界面快速的被组织覆盖,形成严密的连结界面。 结果与结论：抗菌生物材料分为无机抗菌生物材料、天然抗菌生物材料和合成抗菌生物材料,无机抗菌材料以银系材料为主,天然抗菌生物材料以壳聚糖研究为较多,合成抗菌生物材料以季铵盐类材料为代表,各种材料都具有各自的优缺点,需要进一步的体内外基础实验和临床研究来验证和推动抗菌生物材料的发展。     

Present and future applications of biomaterials in controlled drug delivery systems

In this paper we review controlled drug release polymeric systems with emphasis on the polymer carriers as biomaterials. Polymer structure affects the diffusion mechanism and release behaviour of various drugs. Zero-order release can be achieved under certain conditions of polymer preparation and for specific geometric shapes. Physical, physicochemical, diffusive and toxicological tests for biomaterials used in controlled release applications are also discussed.     

Oral bioavailability of silymarin formulated as a novel 3-day delivery system based on porous silica nanoparticles

The purpose of this study was to develop porous silica nanoparticles (PSNs) as a carrier to improve oral bioavailability of poorly water-soluble drugs, using silymarin as a model. PSNs were synthesized by reverse microemulsion and ultrasonic corrosion methods. A 3-day release formulation consisting of a silymarin solid dispersion, a hydrophilic gel matrix and silymarin-loaded PSNs was prepared. In vitro release studies indicated that both the silymarin-loaded PSNs and the 3-day release formulation showed a typical sustained-release pattern over a long period, about 72 h. The in vivo studies revealed that the 3-day release formulation gave a significantly higher plasma concentration and larger area under the concentration-time curves than commercial tablets when orally administered to beagle dogs. This implies that the prepared 3-day release formulation significantly enhanced the oral bioavailability of silymarin, suggesting that PSNs can be used as promising drug carriers for oral sustained release systems. Thus providing a technically feasible approach for improving the oral bioavailability and long-term efficacy of poorly soluble drugs.     

胰岛素缓释载体材料应用研究与问题

BACKGROUND: Sustained-release carriers of insulin shaped as microspheres made of different biomaterials have become an issue of concern. OBJECTIVE: To summarize the carrier materials and methods to prepare sustained-release microspheres of insulin. METHODS: Wanfang and PubMed databases were retrieved by computer for articles related to sustained-release carriers of insulin published from 1997 to 2015. The search terms were “insulin, controlled-release carrier, biomaterials” in Chinese and English, respectively. RESULTS AND CONCLUSION: Natural biodegradable polymer materials are preferred to prepare sustained-release microspheres of insulin, including gelatin, alginate, chitosan and its derivatives. These natural materials have good biocompatibility, degradability, film-forming and microsphere-forming abilities. Synthetic biodegradable polymer materials as carrier materials can promote drug stability and effective utilization, and realize targeted drug delivery. According to different physicochemical properties of materials, sustained-release carriers of insulin that meet different requirements can be prepared using emulsion-chemical crosslinking, spray drying and solvent evaporation methods. This review provides new insight into the development of stable drug carriers.     

Antimicrobial delivery systems for local infection prophylaxis in orthopedic- and trauma surgery

Infectious complications occur in a minor but significant portion of the patients undergoing joint replacement surgery or fracture fixation, particularly those with severe open fractures, those undergoing revision arthroplasty or those at elevated risk because of poor health status. Once established, infections are difficult to eradicate, especially in the case of bacterial biofilm formation on implanted hardware. Local antibiotic carriers offer the prospect of controlled delivery of antibiotics directly in target tissues and implant, without inducing toxicity in non-target organs. Polymeric carriers have been developed to optimize the release and targeting of antibiotics. Passive polymeric carriers release antibiotics by diffusion and/or upon degradation, while active polymeric carriers release their antibiotics upon stimuli provided by bacterial pathogens. Additionally, some polymeric carriers gelate in-situ in response to physiological stimuli to form a depot for antibiotic release. As antibiotic resistance has become a major issue, also other anti-infectives such as silver and antimicrobial peptides have been incorporated in research. Currently, several antibiotic loaded biomaterials for local infection prophylaxis are available for use in the clinic. Here we review their advantages and limitations and provide an overview of new materials emerging that may overcome these limitations.     

Colloidal carrier integrating biomaterials for oral insulin delivery: Influence of component formulation on physicochemical and biological parameters

Strategies to design effective and safe colloidal carriers for biopharmaceuticals have evolved through applying the knowledge gained in nanotechnology to medicine. Designing a colloidal carrier to serve as a protein delivery device requires an understanding of the effect of different materials on the physicochemical, physiological and toxicological parameters for clinical application. The purpose of this study was to evaluate the influence of formulation components on the physicochemical factors and biological function involved in the development and optimization of newly designed nanoparticles for orally dosed insulin. Biodegradable, biocompatible, mucoadhesive and protease-protective biomaterials were combined through ionotropic pre-gelation and polyelectrolyte complexation forming an alginate, dextran sulfate and poloxamer hydrogel containing insulin, stabilized in nanoparticles with chitosan and poly(ethyleneglycol) and coated with albumin. Nanoparticles ranged in size from 200 to 500 nm with 70–90% insulin entrapment efficiency, and electrostatic stabilization was suggested by zeta potential values lower than −30 mV. This combination of formulation components was selected for insulin protection against harsh gastric pH and proteolytic conditions, and to improve insulin absorption through intestinal mucosa by combining nanoparticle uptake and insulin release at the site of absorption. Insulin was shown to be bioactive after nanoparticle formulation and release in neutral pH conditions. Fourier transform infrared spectroscopy was used to confirm the presence of formulations components in the nanoparticle structure and to identify potential interactions between biomaterials.     

Nanomedicine for treatment of diabetes in an aging population: state-of-the-art and future developments

Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients. Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route. In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology. Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy. In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are required for prevention of the disease.     

高分子药用控释及缓释载体材料特点及在高血压治疗中的应用

BACKGROUND: Polymeric material, an important carrier used in the sustained-release and controlled-release system, is a major factor influencing drug efficacy; so understanding of different carrier materials contributes to obtain an ideal control-released effect. OBJECTIVE: To clarify the characters of medical polymeric materials, and analyze their application in the sustained-release and controlled-release system in the treatment of hypertension. METHODS: An online research was performed in databases of PubMed and WanFang for relative literatures published from 2006 to 2015 using the keywords of “polymers; sustained-release material; controlled-release material; chitosan; cyclodextrin; ilk fibroin; poly acid anhydride; polylactic acid” in Chinese and English, respectively. Totally 30 literatures were enrolled for analysis based on the inclusion and exclusion criteria. Analyzing the application tendency of sustained-release and controlled-release system in the treatment of hypertension was conducted by retrieving WanFang database between 2010 and 2015 in China. RESULTS AND CONCLUSION: Polymeric materials used for release carriers should be non-toxic or low toxic and hold good biocompatibility and biodegradability, including natural polymeric materials (polysaccharides and proteins) and synthetic polymeric materials (polylactic acids, polyanhydrides, polypeptides and amino acids). These new polymeric materials overcome some shortcomings of the single material and expand the range of controlled-release carriers showing a light application prospect. Studies on the sustained-release and controlled-release system have achieved satisfactory outcomes, but questions of efficiency, speed-control and intelligentization remain to be resolved. The number of literatures related to the application of sustained-release and controlled-release system in the treatment of hypertension in WanFang database between 2010 and 2015 are increased gradually, suggesting that the sustained-release and controlled-release drugs have become popular in the hypertension treatment. Nifedipine sustained-release or control-release tablets, felodipin sustained-release tablets and metoprolol sustained-release tablets are commonly used.      

形状记忆输卵管避孕材料与其他输卵管避孕材料的特点分析

背景：输卵管绝育器对女性生殖功能及内分泌平衡干扰少,方法简单有效。 目的：阐述形状记忆输卵管避孕材料与其他输卵管避孕材料的优点及不良反应。 方法：应用计算机检索1996至2013年万方医学网、中国知网、PubMed数据库有关形状记忆输卵管避孕材料与其他输卵管避孕材料的文章。 结果与结论：目前应用的输卵管避孕材料主要有记忆金属生物材料、非降解高分子生物材料及可降解高分子生物材料。形状记忆输卵管避孕器植入后,对输卵管上皮具有短期炎性刺激作用,但其对上皮输卵管黏膜层的影响是暂时的,随着植入时间延长,输卵管上皮炎性反应逐渐减退,其管壁的绒毛逐渐修复,表明输卵管再通具有可复性的组织基础。聚乙烯材料具有高抗冲性、耐磨性、优良的对化学药品稳定性、吸水性、电绝缘性、生物惰性等,现在几乎是所有宫内节育器的支架材料。硅橡胶耐热、耐寒、无毒、耐生物老化,具有化学稳定性、生理惰性、物理机械性能,植入人体组织后不会引起异物反应。聚乳酸具有较好的化学惰性、易加工性和的生物相容性,植入体内5 年后仍可能存在。