粒子沥滤法制备组织工程用多孔支架的研究进展

粒子沥滤法作为常用的制备组织工程支架的方法,这种方法对实验设备和实验条件要求较低,孔隙率、孔径可控。但传统的溶液浇铸/粒子沥滤法也存在一些缺点,只适合制备薄层支架,孔-孔连通性不好,聚合物有可能保留致孔剂和/或有毒溶剂。本文总结了近几年科研工作者对这种方法所进行的改进工作,并探讨了改进的效果和不足。     

聚乙二醇对苯二甲酸酯-b-聚对苯二甲酸丁二醇酯多嵌段共聚物内部贯通多孔支架的制备方法

以天然或合成的可生物降解材料制备细胞外基质支架是组织工程所涉及到的关键问题之一.常用的制备方法由于涉及到有机溶剂的使用、较高的加工温度以及致孔剂的残余问题,对于活性物质的引入均带来不利影响,相关的改进工作(如不使用有机溶剂和消除残余致孔剂等)尽管也获得了具有良好孔结构的支架,但却使制备过程更趋复杂.     

微球-三维支架复合体系控制释放生长因子的研究进展

将载生长因子的微球和组织工程三维支架复合得到的微球-三维支架复合体系,能够实现多种生长因子的依次释放和连续释放,满足新组织形成过程中不同阶段对不同量的各种生长因子的需求。在综述了微球和支架作为载体的载生长因子方法及优缺点的基础上,评述了微球-三维支架复合体系的三种制备方法,即自上而下法、复合溶结法和直接混和法,归纳和总结了国内外对微球-三维支架复合体系的研究现状和进展。并阐述了微球-三维支架复合体系的释放机理,指出了微球-三维支架复合体系在理想组织修复中的发展潜力和面临的挑战。     

壳聚糖及其衍生物在组织工程中的应用

壳聚糖由于具有良好的生物相容性、生物可降解性以及具有可反应的活性基团,因而在生物、医学等领域具有广泛的研究和应用。随着组织工程学研究的深入,壳聚糖及其衍生物材料作为天然高分子组织工程支架越来越受到重视,综述了近年来国内外壳聚糖及其衍生物在组织工程上的研究和应用情况,包括壳聚糖及其衍生物支架材料的制备方法、壳聚糖的改性以及壳聚糖复合材料等。     

组织工程用可生物降解聚合物多孔支架制备方法研究进展

可生物降解高分子多孔支架已广泛用作各种再生新组织模板,组织工程要求支架要有着良好的相互连通、高度开放的多孔结构,以实现细胞的增殖和分化。因此,如何把材料加工成满足生物体要求的结构至关重要。本文对最近几年组织工程用高孔隙率三维支架的制备方法进行了综述,并指出了各种方法的优缺点,展望了可降解高分子支架制备方法的发展前景。     

聚乳酸与聚乳酸-羟基乙酸多孔细胞支架的制备及孔隙的表征

应用溶液烧铸致孔剂浸出技术制备了不同致孔剂用量与不同致孔剂颗粒尺寸条件下的一系列聚乳酸及不同组成的聚乳酸－羟基乙酸多孔细胞支架;用一种改进的方法－重量法测定其孔隙率;在聚乳酸－羟基乙酸多孔支架上进行了软骨细胞培养。研究结果表明,随着制备过程中致孔剂用量的增加,多孔支架的孔隙逐渐增加,而与致孔剂的颗粒大小基本无关;致孔剂的颗粒大小只影响多孔支架的孔径;在致孔剂用量及致孔剂颗粒尺寸都相同的情况下,随着共聚物中乙交酯含量的增加,孔隙率逐渐下降;软骨细胞在支架上繁殖情况良好,三周后已开始分泌细胞外基质。     

强韧支架用丝素蛋白基生物墨水及其3D打印支架模拟软件的开发

基于丝素蛋白（SF）和有限元分析方法，开发了一种强韧支架用丝素蛋白基生物墨水及其3D打印支架压缩性能模拟软件。表征了墨水的可打印性及对应水凝胶和3D打印支架的力学性能，评估了相关打印支架的细胞相容性。基于所述丝素蛋白基生物墨水，设计并制备了不同高度和孔隙率的3D打印支架，利用所开发软件和电子万能材料试验机对打印支架的压缩性能进行了模拟预测和实测对比。结果表明：该墨水可打印性佳，对应支架强度高韧性好、细胞相容性好。所开发软件操作简便，具有3D打印支架建模、模型压缩力学性能预测以及指导3D打印支架快速制备等功能。     

组织工程三维多孔支架的制备方法和技术进展

组织工程的关键技术之一在于将具有良好生物相容性和生物降解吸收性能的生物材料制备成具有特定形状和相连孔结构的三维多孔细胞支架（细胞外基质替代物）。本文着眼于多孔支架制备方法分别与多孔支架孔结构和外形的内在联系，从致孔和外形成型两个层次对组织工程多孔支架的制备方法和技术新近的研究进展进行了综述。     

可降解聚氨酯型组织工程多孔支架材料的制备

本文在可降解型聚氨酯分子设计,聚氨酯型组织工程支架制备方法,可降解聚氨酯多孔支架的生物学性能及可降解聚氨酯多孔支架在组织工程中的应用等几个方面对可降解聚氨酯型组织工程支架的最新研究进展作了综述。重点讨论了静电纺丝、冷冻干燥、相分离等几种聚氨酯多孔支架制备方法以及聚氨酯型组织工程支架的生物降解性质、生长因子嵌入、生物力学性能、生物相容性等生物学性能。目前的研究表明通过聚氨酯分子设计与各种支架制备方法结合可制得满足各种生物学性能的支架材料且这类材料已被证实在血管、软骨、硬质骨等各类组织工程中有重要的应用价值。但如何进一步提高聚氨酯支架材料的力学强度以使其能更好地与硬组织的力学性能相匹配以及如何降低或消除聚氨酯对人体的毒性仍是需要进一步研究的问题。     

富勒烯及其衍生物的质谱研究

本文制备了一系列富勒烯及其衍生物，并利用多种质谱技术进行了鉴定、表征、揭示了它们在离子源条件下的稳定性及解规律。这些富勒烯及其省生物在ＦＤＭＳ、ＩＳＭＳ中均得到了较强的准分子离子峰且碎片峰很少。结果表昨ＦＤＭＳ，ＬＳＩＭＳ技术均适于富勒烯及其衍生物的定性分析，是目前富勒烯分析鉴定中较好的方法。     

Electrospinning of ultrafine core/shell fibers for biomedical applications

Because of the inherent appearance similar to the natural extracellular matrix, ultrafine fibrous membranes prepared via electrospinning exhibit widespread applications, especially in the biomedical area. Extensional modifications of coaxial and emulsion electrospinning have drawn much attention in preparation of core/shell fibers for applications as tissue engineering scaffolds and controlled delivery systems for bioactive substances. Due to incorporation of multi-components in the electrospun core/shell fibers, the process of coaxial and emulsion electrospinning became more susceptible. The theories have not been fully understood. A series of investigations were carried out evaluating the systematic and processing parameters. This paper reviews advantages and potentials of electrospun core/shell fibers as well as factors influencing their formation on the basis of our research and new progress.     

A versatile approach toward the ansamycin antibiotics

[STRUCTURE: SEE TEXT] The ansamycin antibiotics contain metacyclophanic macrolactams, many of which possess potent antitumor activity. Only a few total syntheses of this family of natural products have been reported, and modifications to increase potency have not been described. Therefore, a method was developed to prepare the trienomycin A core via resin-bound triphenylphosphonium salts, which serve as both a reagent and a traceless linker to afford olefinic products that undergo ring-closing metathesis (RCM) to give macrocyclic scaffolds of varying ring sizes.     

A Spatially Programmable DNA Nanorobot Arm to Modulate Anisotropic Gold Nanoparticle Assembly by Enzymatic Excision

Programmable assembly of gold nanoparticle superstructures with precise spatial arrangement has drawn much attention for their unique characteristics in plasmonics and biomedicine. Bio-inspired methods have already provided programmable, molecular approaches to direct AuNP assemblies using biopolymers. The existing methods, however, predominantly use DNA as scaffolds to directly guide the AuNP interactions to produce intended superstructures. New paradigms for regulating AuNP assembly will greatly enrich the toolbox for DNA-directed AuNP manipulation and fabrication. Here, we developed a strategy of using a spatially programmable enzymatic nanorobot arm to modulate anisotropic DNA surface modifications and assembly of AuNPs. Through spatial controls of the proximity of the reactants, the locations of the modifications were precisely regulated. We demonstrated the control of the modifications on a single 15 nm AuNP, as well as on a rectangular DNA origami platform, to direct unique anisotropic AuNP assemblies. This method adds an alternative enzymatic manipulation to DNA-directed AuNP superstructure assembly.     

Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety,Privileged Hybrids in Anticancer Drug Discovery

Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.     

Synthesis of Azaspiro Tricyclic Scaffolds through Post-Ugi Modifications: Scope and Limitation of Aza-Michael Cyclization

Post-Ugi modifications offer a great tool to construct functionalized heterocycles in an atom-economic manner. Using this approach, we have constructed highly functionalized azaspiro tricyclic scaffolds that involve Ugi condensation and ipso-cyclization followed by aza-Michael ring closures. Herein, we present a detailed account of aza-Michael cyclizations with respect to substrate scope and limitations, along with new methods to prepare novel azaspiro tricyclic scaffolds.     

Unraveling differences in aluminyl and carbene coordination chemistry: bonding in gold complexes and reactivity with carbon dioxide

The electronic properties of aluminyl anions have been reported to be strictly related to those of carbenes, which are well-known to be easily tunable via selected structural modifications imposed on their backbone. Since peculiar reactivity of gold-aluminyl complexes towards carbon dioxide has been reported, leading to insertion of CO₂ into the Au–Al bond, in this work the electronic structure and reactivity of Au–Al complexes with different aluminyl scaffolds have been systematically studied and compared to carbene analogues. The analyses reveal that, instead, aluminyls and carbenes display a very different behavior when bound to gold, with the aluminyls forming an electron-sharing and weakly polarized Au–Al bond, which turns out to be poorly modulated by structural modifications of the ligand. The reactivity of gold–aluminyl complexes towards CO₂ shows, both qualitatively and quantitatively, similar reaction mechanisms, reflecting the scarce tunability of their electronic structure and bond nature. This work provides further insights and perspectives on the properties of the aluminyl anions and their behavior as coordination ligands.

Aluminyls and carbenes as coordination ligands, although sharing similar electronic properties, reveal fundamental differences in their tunability, bonding to gold and reactivity of their complexes with carbon dioxide.     

A preliminary in silico lead series of 2-phthalimidinoglutaric acid analogues designed as MMP-3 inhibitors

Matrix metalloproteinases (MMPs) have been the subject of intense research because of their roles in tumor metastasis and in the rise and spread of degenerative diseases such as osteo- and rheumatoid arthritis. A preliminary class of 140 druglike, small-molecule matrix metalloproteinase-3 inhibitors, intended as starting scaffolds for optimization and synthesis, has been designed in silico using a series of highly predictive three-dimensional quantitative structure-activity relationship models, including comparative molecular field analysis and comparative molecular similarity indices analysis, with docking and scoring. Thalidomide was chosen as the skeleton on which to base the new lead series, as it moderately inhibits MMP-3, is antiangiogenic, and lends itself easily to structural modifications. Most of the new compounds demonstrate medium to high predicted biological activity and good bioavailability as estimated by the octanol-water partition coefficient ClogP. Compound 102 in particular exhibits extremely favorable predicted activity against MMP-3; is moderately bioavailable; satisfies Lipinski's Rule of Five; and shows promise for further optimization, synthesis, and experimental evaluation as a potential adjunct anticancer or antirheumatic therapeutic.     

Alginate hydrogels as biomaterials

[Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation.     

Oxetanes as versatile elements in drug discovery and synthesis

Sizable resources, both financial and human, are invested each year in the development of new pharmaceutical agents. However, despite improved techniques, the new compounds often encounter difficulties in satisfying and overcoming the numerous physicochemical and many pharmacological constraints and hurdles. Oxetanes have been shown to improve key properties when grafted onto molecular scaffolds. Of particular interest are oxetanes that are substituted only in the 3-position, since such units remain achiral and their introduction into a molecular scaffold does not create a new stereocenter. This Minireview gives an overview of the recent advances made in the preparation and use of 3-substituted oxetanes. It also includes a discussion of the site-dependent modifications of various physicochemical and biochemical properties that result from the incorporation of the oxetane unit in molecular architectures.     

Nanofiber Configuration of Electrospun Scaffolds Dictating Cell Behaviors and Cell-scaffold Interactions

Electrospun nanofibers are of the same length scale as the native extracellular matrix and have been extensively reported to facilitate adhesion and proliferation of cells and to promote tissue repair and regeneration. With a primary focus on tissue repair and regeneration using electrospun scaffolds, only a few studies involved electrospun nanofiber scaffolds directing cell behaviors have been reported. In this study, we prepared electrospun nanofiber scaffolds with distinct fiber configurations, namely, random and aligned orientations of nanofibers, as well as oriented yarns, and investigated their effects on cell behaviors. Our results showed that these scaffolds supported good proliferation and viability of murine fibroblasts. Fiber configuration profoundly influenced cell morpho-logy and orientation but showed no effects on cell proliferation rate. The yarn scaffold had comparable total protein accumulation with the random and aligned scaffolds, but it supported a greater pro-liferation rate of fibroblasts with significantly elevated collagen de-position due to its porous fibrous configuration. Cell-seeded yarn scaffolds showed a greater Young's modulus compared with cell-free controls as early as 1 week. Together with its unique fiber configuration similar to the native extracellular matrix of the myocardium, the yarn scaffold might be a suitable matrix material for modeling cardiac fibrotic disorders.