羟基磷灰石复合支架负载抗菌性药物:药物与支架的相互作用机制

背景:骨修复材料植入后引起的局部感染是最严重的手术并发症之一,提高植入部位的抗菌药物的作用效果是非常必要的.目的:综述基于羟基磷灰石支架载抗菌性药物的方式、抗菌性药物的种类以及药物与支架之间的相互作用,总结该载药体系的发展趋势.方法:检索CNKI数据库、PubMed数据库及Web of Science数据库中收录的相关...     

Intracellular dynamics of cationic and anionic polystyrene nanoparticles without direct interaction with mitotic spindle and chromosomes

The fate of nanomaterials with different sizes and charges in mitotic cells is of great importance but seldom explored. Herein we investigate the intracellular fate of negatively charged carboxylated polystyrene (COOH-PS) and positively charged amino-modified polystyrene (NH(2)-PS) nanoparticles of three different diameters (50, 100 and 500?nm) on cancer HeLa cells and normal NIH 3T3 cells during the cell cycles. The results showed that all the fluorescent PS nanoparticles differing in size and/or charge did not interact with chromosome reorganization and cytoskeleton assembly during the mitotic process in live cells. They neither disturbed chromosome reorganization nor affected the cytoskeleton reassembly in both normal and cancer cells. However, NH(2)-PS at the size of 50?nm caused G1 phase delay and a decrease of cyclin (D, E) expression, respectively. Moreover, NH(2)-PS displayed higher cellular toxicity and NH(2)-PS of 50?nm disturbed the integrity of cell membranes. Both cationic and anionic PS nanoparticles had a more pronounced effect on normal NIH 3T3 cells than cancer HeLa cell. Our research provides insight into the dynamic fate, intracellular behavior, and the effects of nanoparticles on spindle and chromosomes during cell division, which will enable the optimization of design and selection of much safer nanoparticles for lower risk to human health and widely medical applications.     

Adhesion between biodegradable polymers and hydroxyapatite: Relevance to synthetic bone-like materials and tissue engineering scaffolds

Many studies are currently underway on the quest to make synthetic bone-like materials with composites of polymeric materials and hydroxyapatite (HA). In the present work, we use wetting experiments and surface tension measurements to determine the work of adhesion between biodegradable polymers and HA, with specific reference to the role of humid environments. All the polymers are found to exhibit low contact angles (60 degrees ) on the ceramic with work of adhesion values ranging between 48Jm(-2) for poly(epsilon-caprolactone) and 63Jm(-2) for polylactide; these values are associated with physical bonding across the organic/inorganic interface. The corresponding mechanical fracture strengths, measured using four-point bending tests of HA-polymer-HA bonds, scale directly with the results from the wetting experiments. Short-time aging (up to 30h) in a humid environment, however, has a dramatic influence on such HA/polymer interfacial strengths; specifically, water diffusion through the organic/inorganic interface and degradation of the polymer results in a marked decrease, by some 80-90%, in the bond strengths. These results cast doubt on the use of biodegradable polymers/ceramic composites for load-bearing synthetic bone-like materials, as desired optimal mechanical properties are unlikely to be met in realistic physiological environments.     

冠脉支架与血管耦合作用的有限元分析

目的研究支架扩张直径以及斑块硬化程度对支架与冠脉耦合扩张的影响,探究合理的支架扩张直径范围,以期对临床冠脉支架植入术提供科学的参考依据。方法首先采用三维设计软件建立支架和理想狭窄冠状动脉模型,再利用有限元分析软件,通过赋予冠脉斑块3种不同的材料属性(钙化、纤维化、脂质),参考健康冠脉内径尺寸,模拟分析支架分别扩张至冠脉直径的1.0、1.1、1.2、1.3倍时,支架和血管的应力、支架径向回弹率、冠脉最小腔径以及支架的贴壁情况。结果支架、血管壁和斑块上的最大应力、支架径向回弹率、冠脉最小腔径均随支架扩张直径增加而增加。当支架扩张至冠脉直径的1.3倍时,血管壁及钙化斑块上的最大应力已处于或超出极限应力范围;当支架扩张至冠脉直径的1.0倍时,支架卸载回弹后会出现明显的贴壁不良。相比其他两种斑块,钙化斑块导致更高的血管应力和更小的血管腔径增长。结论冠脉支架扩张比例范围在1.1~1.2倍较为合理;其中,含钙化斑块的冠脉,应将支架扩张比例控制在1.1倍更为合理。研究结果可为冠脉支架植入术中支架扩张直径的选择提供参考依据。     

Molecular mechanism of interaction between oligopeptides and double-stranded DNA

Formation of Ala-Glu-Asp-Gly peptide complex with duplex DNA [poly(dA-dT):poly(dAdT)] at neutral pH and ambient temperature was studied experimentally. Peptide binding to duplex DNA was associated with hyperchromic effect indicating local separation of the double helix. Energies of paired interactions between amino acid residues and nucleotide bases were compared with the energy of bond between two bases in the nucleotide pair (dA-dT). A new concept of interaction between two types of informationcarrying molecules is put forward. This interaction underlies triggering of protein synthesis mechanism and can explain the emergence of life on the Earth. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 443–447, April, 2006     

Gelatin functionalization with tyrosine derived moieties to increase the interaction with hydroxyapatite fillers

Combining gelatins functionalized with the tyrosine-derived groups desaminotyrosine or desaminotyrosyl tyrosine with hydroxyapatite (HAp) led to the formation of composite materials with much lower swelling ratios than those of the pure matrices. Shifts of the infra-red (IR) bands related to the free carboxyl groups could be observed in the presence of HAp, which suggested a direct interaction of matrix and filler that formed additional physical cross-links in the material. In tensile tests and rheological measurements the composites equilibrated in water had increased Young's moduli (from 200 kPa up to 2 MPa) and tensile strengths (from 57 kPa up to 1.1 MPa) compared with the matrix polymers without affecting the elongation at break. Furthermore, an increased thermal stability of the networks from 40 to 85°C could be demonstrated. The differences in the behaviour of the functionalized gelatins compared with pure gelatin as a matrix suggested an additional stabilizing bond between the incorporated aromatic groups and the HAp as supported by the IR results. The composites can potentially be applied as bone fillers.     

Protein interaction with tantalum: changes with oxide layer and hydroxyapatite at the interface.

For metallic implants the surface nature is extremely important because blood and tissue interactions with metal depend upon it. Protein adsorption is the initial reaction that takes place when an implant comes in contact with blood or tissue. We attempted to coat different thicknesses of oxide layers and hydroxyapatite on tantalum and examined the changes in water contact angle and adsorption of albumin and fibrinogen. Protein adsorption studies were performed with 125I-labeled proteins. A decrease in water contact angle was observed as the oxide layer thickness of tantalum increased. Fibrinogen adsorption increased on oxide layer coated and hydroxyapatite coated surfaces, compared to bare tantalum.     

Molecular simulation of protein adsorption and desorption on hydroxyapatite surfaces

Protein adsorption and desorption on material surfaces play a key role in the biocompatibility of medical implants, biomineralization and protein separation. In this report, the adsorption and desorption behavior of the 10th type III module of fibronectin (FN-III(10)) with different orientations on hydroxyapatite (HAP) (001) surface were systematically studied by molecular dynamics (MD) and steered MD simulations. These studies show that the electrostatic energy plays a dominant role in the interaction between the model protein and the HAP surface. The values of the interaction energy not only relates to the number of adsorbed sites but also the type. The charged -COO(-) and -NH(3)(+) are the strongest groups that interact with the surface, while other groups like charged guanido group, neutral amino and hydroxyl groups have considerable interactions with the surface. The effects of these groups on interaction energy were quantitatively investigated.     

Probing the weak interaction of proteins with neutral and zwitterionic antifouling polymers

Protein–polymer interactions are of great interest in a wide range of scientific and technological applications. Neutral poly(ethylene glycol) (PEG) and zwitterionic poly(sulfobetaine methacrylate) (pSBMA) are two well-known nonfouling materials that exhibit strong surface resistance to proteins. However, it still remains unclear or unexplored how PEG and pSBMA interact with proteins in solution. In this work, we examine the interactions between two model proteins (bovine serum albumin and lysozyme) and two typical antifouling polymers of PEG and pSBMA in aqueous solution using fluorescence spectroscopy, atomic force microscopy and nuclear magnetic resonance. The effect of protein:polymer mass ratios on the interactions is also examined. Collective data clearly demonstrate the existence of weak hydrophobic interactions between PEG and proteins, while there are no detectable interactions between pSBMA and proteins. The elimination of protein interaction with pSBMA could be due to an enhanced surface hydration of zwitterionic groups in pSBMA. New evidence is given to demonstrate the interactions between PEG and proteins, which are often neglected in the literature because the PEG–protein interactions are weak and reversible, as well as the structural change caused by hydrophobic interaction. This work provides a better fundamental understanding of the intrinsic structure–activity relationship of polymers underlying polymer–protein interactions, which are important for designing new biomaterials for biosensor, medical diagnostics and drug delivery applications.     

Nanocomposites of hydroxyapatite with aspartic acid and glutamic acid and their interaction with osteoblast-like cells

The direct synthesis of hydroxyapatite (HA)-aspartic acid (ASP) and HA-glutamic acid (GLU) nanocrystals was carried out in presence of different amounts of the amino acids in solution. ASP and GLU incorporation into HA crystals reduces the coherent length of the perfect crystalline domains along the long dimension (002) and, even more, along the cross section (310) of the apatite crystals, suggesting a specific interaction of the amino acids with the HA structure. FTIR analysis indicates that the carboxylic groups of the acidic amino acids interact with the calcium ions of HA. The relative amount of ASP incorporation into HA nanocrystals is greater than that of GLU, suggesting a greater affinity of ASP for HA. Osteoblast-like, MG63, cells cultured on the composite nanocrystals display good proliferation and increased values of ALP activity, collagen type I, TGF-betaI and osteocalcin production, indicating that the presence of the acidic amino acids enhances osteoblast activation and extra-cellular matrix mineralization processes.     

Cell-to-cell interaction of Streptococcus sanguis and Propionibacterium acnes on saliva-coated hydroxyapatite.

Cell-to-cell interaction (coaggregation) between Propionibacterium acnes PK93 and Streptococcus sanguis DL1 was measured on saliva-coated hydroxyapatite beads (SHA) at bacterial concentrations between 1.3 X 10(6) and 6.7 X 10(8) cells per ml. Four hundredfold more DL1 than PK93 cells adhered to the saliva-coated beads, and the adherence of S. sanguis was proportional to cell input. SHA precoated with 3 X 10(8) DL1 cells bound 75 to 80% of available PK93 cells at all input amounts tested, up to an input of 8 X 10(7) cells. Adherence of PK93 to DL1-coated SHA approached saturation at an input of approximately 10(9) PK93 cells, when 1.5 X 10(8) bound. The coaggregation on SHA occurred either in buffer or saliva and was inhibited by N-acetylgalactosamine and by lactose; the attachment of DL1 to SHA was not inhibited by these sugars. S. sanguis 34 and heat-treated DL1 cells, neither of which form coaggregates with PK93, attached to SHA, but such cells did not bind PK93 cells. The findings of this study indicate that bacteria unable to attach to saliva-coated hydroxyapatite can indeed adhere to such a surface by strong lectin-mediated cell-to-cell interactions with bacteria already attached to the surface.     

基于骨和无有机成分骨与羟基磷灰石压缩性能实验比较的强度分析

目的分析判定以珊瑚为基体,通过水热交换法制成的羟基磷灰石植入体内后的强度是否可以达到活体骨的水平。方法实验测量羟基磷灰石、含有机成分的骨、无有机成分的骨的压缩极限应力。通过对比羟基磷灰石、骨及无有机成分的骨的压缩强度差别,确定胶原纤维对骨压缩强度的作用,进而应用经验模型预估人造羟基磷灰石在一定空隙度(0.1～0.5)范围变化时的强度。结果羟基磷灰石、骨及无有机成分的压缩强度分别为14.1 GPa、207 GPa和31.7 GPa。结论去除骨中的有机成分后其压缩强度降低约80%。水热交换法制成的羟基磷灰石抗压强度可能高于骨内羟基磷灰石,这种骨替代材料植入体内后,随着骨和纤维组织在内部生长,其强度有可能达到活体骨的水平。     

Structural analysis of the interaction between Shiga toxin B subunits and linear polymers bearing clustered globotriose residues

We previously developed linear polymers bearing clustered trisaccharides of globotriaosylceramide (Gb3) as orally applicable Shiga toxin (Stx) neutralizers. Here, using a Gb3 polymer with a short spacer tethering the trisaccharide to the core, we found that shortening the spacer length markedly reduced the binding affinity for Stx2 but not Stx1. Moreover, mutational analysis revealed that the essential binding sites of the terminal trisaccharides were completely different between Stx1 and Stx2. These results provide the molecular basis for the interaction between Stx B subunits and Gb3 polymers.     

Plasma-sprayed carbon nanotube reinforced hydroxyapatite coatings and their interaction with human osteoblasts in vitro

Carbon nanotubes (CNT) possess excellent mechanical properties to play the role as reinforcement for imparting strength and toughness to brittle hydroxyapatite (HA) bioceramic coating. However, lack of processing technique to uniformly distribute multiwalled CNTs in HA coating and limited studies and sparse knowledge evincing toxicity of CNTs has kept researchers in dispute for long. In the current work, we have addressed these issues by (i) successfully distributing multiwalled CNT reinforcement in HA coating using plasma spraying to improve the fracture toughness (by 56%) and enhance crystallinity (by 27%), and (ii) culturing human osteoblast hFOB 1.19 cells onto CNT reinforced HA coating to elicit its biocompatibility with living cells. Unrestricted growth of human osteoblast hFOB 1.19 cells has been observed near CNT regions claiming assistance by CNT surfaces to promote cell growth and proliferation.     

In vitro interaction between primary bone organ cultures, glass-ionomer cements and hydroxyapatite/tricalcium phosphate ceramics.

Primary organ cultures derived from neonate rat calvaria were maintained for 2 wk and used to study in vitro response of osteoblast and periosteal cells to the component and composite forms of three different glass-ionomer (polyalkenoic) cements, comparing them to densely sintered hydroxyapatite and tricalcium phosphate ceramics. Qualitative analysis by scanning and transmission electron microscopy revealed that osteoblasts colonized all the solid test materials, although there was a less favourable response to materials with a rough surface topography and to unset and fluoride-containing glasses. On solid materials migrated cells maintained their tessellated morphology and exhibited numerous micro-appendages anchoring them to the surface of the test materials. A collagen-containing extracellular matrix was elaborated on to the ceramics and set glass-ionomer cements, except for one (AquaCem). Mineralization of the extracellular matrix was seen adjacent to hydroxyapatite and tricalcium phosphate ceramics, that adjacent to the latter morphologically resembling bone.     

The interaction of plasma proteins with polymers. I. Relationship between polymer surface energy and protein adsorption/desorption

Adsorption of bovine albumin, gamma-globulin and fibrinogen from phosphate buffer solution (pH = 7.5) onto several polymer films was studied using the radioiodinated proteins (125I). The kinetics of desorption of the proteinated polymer films in bovine plasma was determined. Contact angle measurements on these same polymers allowed the calculation of dispersive (WA d) and polar (Ip) components of the polymer-protein solution system. Results from these measurements show that the nondispersive-dispersive force balance at the polymer-protein solution interface, expressed by the Ip/WA d ratio, is an important factor for binding of proteins on polymer surfaces. The purity of fibrinogen and the cleaning procedures for the polymer surfaces influence the absolute values of proteins adsorbed on polymer surfaces.     

The influence of joint position on the dynamics of perception-action coupling

Six right-handed subjects performed rhythmic flexion and extension movements of the index finger in time with an auditory metronome. On each block of trials, the wrist of the response hand was placed in a extended, neutral or flexed position. In the flex-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger flexion with each beat of the metronome. In the extend-on-the-beat condition, subjects were instructed to coordinate maximum excursion in the direction of finger extension with each beat of the metronome. The frequency of the metronome was increased from 2.00 Hz to 3.75 Hz in 8 steps (8 s epochs) of 0.25 Hz. During trials prepared in the extend-on-the-beat pattern, all subjects exhibited transitions to either a flex-on-the-beat pattern or to phase wandering as the frequency of pacing was increased. The time at which these transitions occurred was reliably influenced by the position of the wrist. Four subjects exhibited qualitative departures from the flex-on-the-beat pattern at pacing frequencies that were greater than those at which the extend-on-the-beat pattern could be maintained. The time at which these departures occurred was not influenced by the position of the wrist. These results are discussed with reference to the constraints imposed on the coordination dynamics by the intrinsic properties of the neuromuscular-skeletal system. Received: 1 October 1997 / Accepted: 20 March 1998     

Molecular interaction between nitric oxide and ryanodine receptors of skeletal and cardiac sarcoplasmic reticulum

In striated muscle, the sarcoplasmic reticulum (SR) is the major storage compartment of intracellular Ca2+ that controls cytosolic free Ca2+ (Cai) and developed force by sequestering and releasing Ca2+ during each contraction. Ca2+ release from the SR occurs through high-conductance Ca2+ release channels or ryanodine receptors (RyR), which are regulated by various signaling processes. Over the last 15 years, there has been a growing consensus that critical sulfhydryl sites on RyRs can be oxidized and reduced, respectively, to open and close the release channels. The pharmacological actions of various classes of sulfhydryl reagents have demonstrated the existence of hyperreactive thiols on RyRs, which could play a role in the regulation of normal contractile function and explain contractile dysfunctions in pathological conditions. More recent studies show that redox regulation of release channels may occur by nitric oxide (NO), a physiological signaling mechanism. This article is intended to review current concepts in thiol regulation of RyRs and present new data on the possible identification of the primary cysteine residues, which may be the site of oxidation and S-nitrosylation involved in channel opening.     

Exploring the interaction between FGF Genes and T-box genes among chinese nonsyndromic cleft lip with or without cleft palate case-parent trios

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Genetic variants causing syndromic orofacial clefts can also contribute to the etiology of NSCL/P. The purpose of the present study was to explore gene–gene (G × G) interaction using common single nucleotide polymorphic (SNP) markers in fibroblast growth factor (FGF) family and its receptors and T-box genes, which were associated with syndromic orofacial clefts. Our study was conducted in 806 Chinese NSCL/P case-parent trios drawn from an international consortium. A total of 252 SNPs in FGF8, FGF10, FGFR1, FGFR2, and TBX5 passed the quality control criteria and were included in the analysis. The interactions between SNPs in different genes were assessed using Cordell's method, which fitted a conditional logistic regression model. The analysis was performed using the R-package trio (Version 3.8.0). Bonferroni correction was used to adjust for multiple comparisons, and the overall significance threshold was set as P = 1.98 × 10⁻⁴ (0.05/252). Conditional logistic regression revealed the most significant interaction between rs2330542 in FGF10 and rs1946295 in TBX5, which remained significant (P = 9.63 × 10⁻⁶) after Bonferroni correction. The relative risk of allele C in rs2330542 (FGF10) was 1.02 (95%CI 0.81–1.28), while the relative risk was 1.42 (95%CI 1.03–1.97) when the exposure was a combination of allele C in rs2330542 and allele A in rs1946295 (TBX5). Our findings confirmed the importance of considering G × G interaction when exploring the genetic risk factors of NSCL/P. Further investigations are warranted to validate the potential interaction and reveal the biological function of FGF10/FGFR2/TBX5. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.     

Tensile strength of the interface between hydroxyapatite and bone.

Tensile strength of the interface between hydroxyapatite (HA) and bone was tested. Scanning electron microscopy was used to observe the tensile failure mode and the morphological change of hydroxyapatite ceramic surface in bone. The porosity of hydroxyapatite is 14% and pore size less than 2 microns. After 2 weeks of implantation, the tensile strength of the interface is 0.72 MPa. After 4, 8, and 16 weeks, the average tensile strength stayed at 1.5 MPa. SEM showed that tensile failure occurred at the HA-bone interface at the second week, but after 4 weeks, the failure occurred between HA particles within the bulk, and not at the HA-bone interface. Calcified tissue was directly deposited on the HA ceramic surface and exits also in the micropores. Near the interface, sintered necks among HA ceramic particles were subjected to biodegradation.