Synthesis of 2-pyridones as tissue factor VIIa inhibitors

2-Pyridones were prepared from 2,6-dibromopyridine via a multi-step synthesis. A variety of chemical transformations, including regioselective nucleophilic addition and selective nitrogen alkylation, afforded the penultimate intermediate 9. A combination of two-dimensional NMR techniques to unequivocally assign the structure of 9 is described. Compound 9 was then used in a Suzuki coupling and further derivatized to afford the targeted tissue Factor VIIa inhibitors. These compounds were tested in several serine protease enzyme assays with biological activity reported.     

肽自组装水凝胶的制备及在生物医学中的应用

短肽自组装水凝胶作为一种新型的生物材料,具有生物相容性高、免疫原性低、含水量高、降解产物可被机体重吸收利用、结构与天然细胞外基质类似等优点,使其在材料科学、生物医药及临床医学等领域具有广阔的应用前景。在这篇综述中,我们主要介绍了常用的几种制备稳定的肽自组装水凝胶方法,包括酶催化的水凝胶化、化学/物理交联的水凝胶化以及光催化的水凝胶化。进一步,我们介绍一些关于肽自组装水凝胶在药物递送和抗肿瘤治疗、抗菌和伤口愈合以及3D生物打印和组织工程中的应用。我们希望通过本文的论述能引起更多的人对肽自组装水凝胶的关注,以推进其在生物医学领域应用的发展。     

Green synthesis of Ag/Fe3O4 nanoparticles using Mentha extract: Preparation,characterization and investigation of its anti-human lung cancer application

In this study, silver nanoparticles (Ag NPs) were decorated on the surface of magnetic nanoparticles in an eco-friendly pathway applying Mentha extract as reducing/stabilizing agent. The morphological and physicochemical features of the prepared Ag/Fe₃O₄nanocomposite were determined using several advanced techniques. Hence, our protocol is green and advantageous in terms of- i) biochemical modified biocompatible nanocomposite; ii) nanomaterial providing high surface area and larger number reactive sites; iii) very simplistic synthetic procedure; vi) very low load of metal in the composite and v) high yield in short time. In the medicinal part, the anticancer properties of Ag/Fe₃O₄ nanocomposite against lung cancer cell lines were determined. The free radical for the antioxidant effects was DPPH. The IC₅₀ of Ag/Fe₃O₄ nanocomposite was 200 µg/ml in the antioxidant test. The IC₅₀ of the Ag/Fe₃O₄ nanocomposite were 183, 176, 169, and 125 µg/mL against lung cancer (NCI-H661, NCI-H1975, NCI-H1573, and NCI-H1563) cell lines, respectively. In addition, the current study offer that Ag/Fe₃O₄ nanocomposite could be a new potential adjuvant chemopreventive and chemotherapeutic agent against cytotoxic cells.     

HPMC crosslinked chitosan/hydroxyapatite scaffolds containing Lemongrass oil for potential bone tissue engineering applications

The chitosan (CS), hydroxypropyl methyl cellulose (HPMC), hydroxyapatite (HAp and Lemon grass oil (LGO) based scaffolds was prepared by freeze gelation method. The composite formation was confirmed by FTIR (Fourier-transform infrared spectroscopy) analysis and surface morphology was evaluated by SEM (Scanning Electron Microscopy) analysis. The mechanical strength, biodegradation, swelling, porosity and antibacterial activity were evaluated on the basis of LGO contents. The scaffold structure was porous and the mechanical strength was enhanced as a function of LGO contents. The scaffold properties analysis revealed the biodegradation nature and swelling behavior of CS-HPMC-HAp-LGO was also affected significantly as a function of LGO contents. The cytotoxicity of CS-HPMC-HAp-LGO was studied against MC3T3-E1 cells and based on cell viability, no toxic sign was observed. The antimicrobial activity was evaluated against S. aureus and CS-HPMC-HAp-LGO scaffolds showed promising activity, which was varied as a function of LGO contents. The findings revealed that the CS-HPMC-HAp-LGO are biocompatible and have potential for bone tissue engineering.     

Valve Tissue Engineering with Living Absorbable Threads

Tissue engineering (TE) depends on the population of scaffolds with appropriate cells, arranged in a specific physiological direction using a variety of techniques. Here, a novel technique of creating “living threads” is described based on thin (poly(ε‐caprolactone) fibers of different diameters (23–243 μm). The fibers readily attract human mesenchymal stem cells (MSCs), which are firmly adhered. These versatile fibers can be used to produce dimensional shapes identical in shape to the cup‐like structure of a normal human valve, while preserving the specific orientation of both the cells and the fibers. The MSCs on leaflets and the cells cultured in flask shown similar epitopes expression when analyzed by fluorescence activated cell sorting. Together, these characteristics have important functional implications as living absorbable fibers can be a valuable resource in TE of living tissues, including heart valves.

     

A Modified Polysaccharide‐Based Hydrogel for Enhanced Osteogenic Maturation and Mineralization Independent of Differentiation Factors

Bone related problems are increasing as a consequence of increased life expectancy, disorders in life style, and other medical conditions enforcing the need for functional bones prepared in vitro at affordable cost. Lack of suitable surface which promotes growth of both osteogenic and nonosteogenic cells is a major limitation. Here a novel biomaterial is reported that is synthesized from natural polysaccharide, namely, tamarind kernel polysaccharide (TKP), which is grafted with hydrophilic acrylic acid (AA) by radical polymerization. Modification in surface functionality removes unwanted proteins and alters hydrophilic/hydrophobic balance. TKP‐AA is suitable for the growth of different nonosteogenic and osteogenic cells. This material is suitable for osteoblasts and promotes in vitro mineralization and differentiation without the addition of exogenous growth factors. TKP‐AA can be used for the growth of mesenchymal stem cell‐derived osteoblasts. It is suggested that TKP‐AA can potentially be used as a scaffold for diverse cell types and particularly for bone tissue engineering at low cost.

     

Nano‐Bio Engineered Carbon Dot‐Peptide Functionalized Water Dispersible Hyperbranched Polyurethane for Bone Tissue Regeneration

The present study delves into a combined bio‐nano‐macromolecular approach for bone tissue engineering. This approach relies on the properties of an ideal scaffold material imbued with all the chemical premises required for fostering cellular growth and differentiation. A tannic acid based water dispersible hyperbranched polyurethane is fabricated with bio‐nanohybrids of carbon dot and four different peptides (viz. SVVYGLR, PRGDSGYRGDS, IPP, and CGGKVGKACCVPTKLSPISVLYK) to impart target specific in vivo bone healing ability. This polymeric bio‐nanocomposite is blended with 10 wt% of gelatin and examined as a non‐invasive delivery vehicle. In vitro assessment of the developed polymeric system reveals good osteoblast adhesion, proliferation, and differentiation. Aided by this panel of peptides, the polymeric bio‐nanocomposite exhibits in vivo ectopic bone formation ability. The study on in vivo mineralization and vascularization reveals the occurrence of calcification and blood vessel formation. Thus, the study demonstrates carbon dot/peptide functionalized hyperbranched polyurethane gel for bone tissue engineering application.

     

Modélisation probabiliste d'une expérience ultrasonore : calcul de la dispersion sur les mesures de célérité

This Note presents a probabilistic model of transient wave reflection at a fluid–solid interface. The configuration represents an ultrasonic experiment used for bone tissue evaluation. The parametric method is used to derive the probabilistic model for the mechanical parameters of the solid (bone); the associated random variables are derived according to the maximum entropy principle. A Monte Carlo simulation, associated with the Cagniard–de Hoop method to calculate the acoustic response, yields the probability density for an output ultrasonic parameter similar to the velocity of longitudinal waves in the solid. Results demonstrate the sensitivity of the probability density of this parameter to the experimental setup. To cite this article: K. Macocco et al., C. R. Mecanique 333 (2005).     

Engineering mechanical-electrical cell microenvironment in myocardium using advanced biomaterials

心血管疾病是当前全球范围内导致人类死亡的首要原因, 心肌组织工程的发展为心血管疾病的治疗, 尤其是心肌组织再生修复提供了最有潜力的解决方案.心血管疾病的发生发展与细胞力--电微环境的变化密切相关. 近十几年, 随着先进生物材料和微纳生物制造技术的发展, 越来越多的研究表明, 细胞力--电微环境的调控对工程化心肌组织的成熟和功能化以及心肌组织再生修复具有重要意义. 本文首先阐明了在体心肌细胞所处力学微环境的生物学基础以及电信号的传导过程, 包括正常和疾病状态下心肌细胞所处的力--电微环境.其次调研了用于心肌组织工程的先进生物材料的研究现状.最后总结用于基底硬度与应力应变细胞微环境以及细胞电学微环境的构建和调控, 以及细胞对力--电微环境的生物学响应.%     

Sur le remodelage des tissus osseux anisotropesOn the remodelling of anisotropic bone tissue

Growth (change of relaxed lengths) and remodelling (change of mechanical properties) are both involved in the morphogenesis of biological tissues. To model them is of paramount import for progressing both in scientific understanding and health technologies. We model bone tissue as a microstructured continuum, whose mechanical properties at the macroscopic scale are described by a linear, anisotropic elastic response that evolves in time. Our kinematics is rich enough to allow for the microstructural evolution, as well as for the interplay between stress, growth and remodelling. This is a unified approach to the mechanics of growth and remodelling, in which all balance laws derive from one virtual-power principle. As a first application, we study the problem of stiffness remodelling due to planar rotation of the microstructure, excluding bulk growth and all physiological response to mechanical stimuli (passive remodelling). To cite this article: A. DiCarlo et al., C. R. Mecanique 334 (2006).