bluuebunny/crossref_metadata_2025 huggingface dataset:
1,3,2‐Oxazastibinanes: Novel six‐membered heterocycles
Authors: Singh Satnam , Jha N. K.
Published: June 2003

The hitherto unreported oxazastibinanes 3 have been synthesized by the sodium borohydride reduction of 3‐phenyl‐1‐arylamino‐3‐oxopropane (1) and subsequent cyclization of the disodium salt of 3‐phenyl‐1‐arylamino‐3‐hydroxypropane (2) with R3SbBr2 (R = Ph, p‐tolyl, or mesityl). These compounds have been characterized by elemental analyses, molecular weight determination, and by IR, far IR, 1H, and 13C NMR spectral studies. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:417–420, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10155
1,3,4‐Thia‐ and ‐selenadiazole and 1,2,4‐triazolo[4,3‐a]pyrimidine derivatives from hydrazonoyl halides
Authors: Abdel‐Riheem Nadia A. , Rateb Nora M. , Al‐Atoom Ali A. , Abdelhamid Abdou O.
Published: June 2003

1,2,4‐Triazolo[4,3‐a]pyrimidines, thiadiazolines, selenadiazolines, and unsymmetrical azines were synthesized via reactions of a 4‐isopropylbenzoyl bromide 4‐nitrophenylhydrazone with each of potassium thiocyanate, potassium selenocyanate, ethyl 6‐methyl‐4‐[4‐(methylethyl)phenyl]‐2‐methylthio‐3,4‐dihydropyrimidine‐5‐carboxylate, and alkyl carbodithioate. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:421–426, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10156
Syntheses of 3,4,7‐triazaacenaphthylene and pyrido[3,4,5‐de]cinnoline derivatives
Authors: Elassar Abdel‐Zaher A. , El‐Kholy Yehya M.
Published: June 2003

The title compounds were prepared by four different routes: (1) reaction of cycloalkanopyridazines 3a–e with trichloroacetonitrile in basic medium; (2) reaction of 3a–d with DMF DMA, followed by nucleophilic treatment with a primary amine; (3) reaction of 2‐(dimethylamino)methylene‐cycloalkylidene‐malononitrile with arene diazonium salt, followed by amine treatment; (4) reaction of cycloalkylidenemalononitrile with phenyl or benzoyl isothiocyanate and heating the product with diazoaminobenzene. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:427–433, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10168
Conversion of 2(3H)‐furanones bearing indole nuclei into novel amide, pyrrolone, and imidazole derivatives
Authors: Hamad Elgazwy Abdel‐Sattar S. , Zaky H. T. , Mohamed M. I. , Ahmed H. M. , Kandile N. G.
Published: June 2003

2(3H)‐Furanones 1a–d having exocyclic double bond and N‐acetylisatin nucleus were converted into the corresponding novel amides, pyrrolones, and imidazoles via nitrogen nucleophiles. All purposed structures were confirmed by NMR, mass spectra GC/MS, and chemical evidence. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:434–442, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10175
Fragmentation‐related phosphinylations using 2‐aryl‐2‐phosphabicyclo[2.2.2]oct‐ 5‐ene‐ and ‐octa‐5,7‐diene 2‐oxides
Authors: Keglevich György , Szelke Helga , Bálint Ágnes , Imre Tímea , Ludányi Krisztina , Nagy Zoltán , Hanusz Miklós , Simon Kálmán , Harmat Veronika , Tőke László
Published: June 2003

A series of new P‐methylphenyl P‐heterocycles are introduced. The para and ortho substituted 2,5‐dihydro‐1H‐phosphole oxides (1a and 1b) were converted to the double‐bond isomers (A and B) of 1,2‐dihydrophosphinine oxides (3a and 3b) via the corresponding phosphabicyclo[3.1.0]hexane oxides (2a or 2b). Isomeric mixture (A and B) of the dihydrophosphinine oxides (3a and 3b) gave, in turn, the isomers (A and B) of phosphabicyclo[2.2.2]oct‐5‐enes (4a and 4b) or a phosphabicyclo[2.2.2]octa‐5,7‐diene (5) in Diels‐Alder reaction with dienophiles. The bridged P‐heterocycles (4 and 5) were useful in the photo‐ or thermoinduced fragmentation‐related phosphinylation of hydroxy compounds and amines. The new precursors (4a and 4b) were applied in mechanistic investigations. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:443–451, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10176
Dichloro(diisopropylamino)phosphonio[5(4H)oxopyrazol‐4‐ylide‐5‐one]: Synthesis and properties
Authors: Konovets A. I. , Kostyuk A. N. , Pinchuk A. M. , Tolmachev A. A. , Fischer A. , Jones P. G. , Schmutzler R.
Published: June 2003

Chlorination of the 4‐[chloro(diisopropylamino)phosphino]pyrazole 1 leads to the dichlorophosphonium chloride 2, which immediately after its formation transforms into the dichloro(diisopropylamino)phosphonio[5(4)oxopyrazol‐4‐ylide‐5‐one] 3, as a result of dealkylation through loss of ethyl chloride.
Reactions of 3 with various nucleophilic reagents were studied. The partial hydrolysis of 3 in the presence of nitriles, resulting in new phosphorus‐containing cyclic systems, is of particular interest. It was demonstrated that chlorination of the P‐dichloropyrazolylphosphine A leads to the stable tetrachlorophosphorane 12. The CP bond of 12 is broken upon heating. An X‐ray structure determination of compound 11b revealed a planar central heterocycle (mean deviation 0.029 Å). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:452–458, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10177
Utility of a 2‐aminothiophene‐3‐carboxamide in the synthesis of thienopyridines and thienopyrimidines
Authors: Mohareb Rafat M. , Sherif Sherif M. , Gaber Hatem M. , Ghabrial Sami S. , Aziz Susan I.
Published: June 2003

2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]‐ thiophene‐3‐carboxamide (1) was prepared according to Gewald procedure. Its reactivity toward a variety of chemical reagents was studied to give thienopyridines and ‐pyrimidines. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:459–467, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10179
Solvent‐free cycloaddition reaction of 3‐indolylimines with chloroacetyl chloride under microwave irradiation
Authors: Dandia Anshu , Singh Ruby , Sharma Pragati
Published: June 2003

Solvent‐free approach is developed for the rapid synthesis of spiro[azetidine‐indoles] 6a–g on basic alumina supported potassium carbonate (K2CO3–Al2O3) from the cycloaddition reaction of indolylimines 3 and chloroacetyl chloride 4 as synthons using microwaves. The procedure neither required toxic and hazardous base nor volatile solvents. 3 was synthesized in situ by the neat reaction of indole‐2,3‐diones 1 and fluorinated anilines 2 under microwave irradiation. Solvent‐free aminoalkylation of spiro compounds 6a and 6b has been carried out under microwaves. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:468–473, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10180
Cycloaddition of N‐(2,2,2‐trichloroethylidene)‐substituted carboxamides and carbamates to 1,2,4‐thiadiazol‐5(2H)‐imines
Authors: Zyabrev Vladimir S. , Rensky Mikhail A. , Rusanov Eduard B. , Drach Boris S.
Published: June 2003

1,2,4‐Thiadiazol‐5(2H)‐imines 4 react with N‐(2,2,2‐trichloroethylidene)‐substituted amides 5 to form [3 + 2]‐cycloaddition products 6 featured by an extra coordination of the ring sulfur atom to the terminal nitrogen atom of the side 1,3‐diazapropenylidene group, as established by X‐ray diffraction investigation. This coordination evidently plays an important role in the alkylation of compounds 6 into 8 at the oxygen atom under mild conditions. The SN bond “switch‐over” restoring the original 1,2,4‐thiadiazole ring occurs therewith. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:474–480, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10182
A report on the 29th symposium on heteroatom chemistry of the chemical society of Japan
Authors: Ishii Akihiko , Sugihara Yoshiaki , Nakayama Juzo
Published: June 2003

The 29th domestic Chemical Society of Japan Symposium on Heteroatom Chemistry was held in Hiroshima during the period of December 12–14, 2002, under the management of Tetsuo Otsubo of Hiroshima University. About 250 chemists from various academic institutes and industries enjoyed four plenary lectures, 44 oral presentations, and 53 poster presentations. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:387–398, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10186
Suspended sediment dynamics in a steep, glacier‐fed mountain stream, Place Creek, Canada
Authors: Richards G. , Moore R. D.
Published: June 2003

This study examined suspended sediment concentration (SSC) during the ablation seasons of 2000 and 2001 in Place Creek, Canada, a steep, glacier‐fed mountain stream. Comparison of stream flow in Place Creek with that in an adjacent, almost unglacierized catchment provided a rational basis for separating the ablation seasons into nival, nival–glacial, glacial and autumn recession subseasons. Distinct groupings of points in plots of electrical conductivity against discharge supported the validity of the subseasonal divisions in terms of varying hydrological conditions. Relationships between SSC and discharge (Q) varied between the two study seasons, and between subseasons. Hysteresis in the SSC–Q relationship was evident at both event and weekly time‐scales. Some suspended sediment released from pro‐glacial Place Lake (the source of Place Creek) appeared to be lost to channel storage at low flows, especially early in the ablation season, with re‐entrainment at higher flows. Multiple regression models were derived for the subseasons using predictor variables including Q, Q2, the change in Q over the previous 3 h, cumulative discharge over the ablation season, total precipitation over the previous 24 h and SSC measured at 1500 hours as an index value for each day. The models produced adjusted R2 values ranging from 0·71 to 0·91, and provided tentative insights into the differences in SSC dynamics amongst subseasons. Introduction of the index value of SSC significantly improved the model fit during the nival–glacial and glacial subseasons for both years, as it adjusts the model to the current condition of sediment supply. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of spatial variation characteristics on contouring of design storm depth
Authors: Cheng Ke‐Sheng , Wei Chiang , Cheng Yen‐Ben , Yeh Hui‐Chung
Published: June 2003

The ordinary kriging method, a geostatistical interpolation technique, was applied for developing contour maps of design storm depth in northern Taiwan using intensity–duration–frequency (IDF) data. Results of variogram modelling on design storm depths indicate that the design storms can be categorized into two distinct storm types: (i) storms of short duration and high spatial variation and (ii) storms of long duration and less spatial variation. For storms of the first category, the influence range of rainfall depth decreases when the recurrence interval increases, owing to the increasing degree of their spatial independence. However, for storms of the second category, the influence range of rainfall depth does not change significantly and has an average of approximately 72 km. For very extreme events, such as events of short duration and long recurrence interval, we do not recommend usage of the established design storm contours, because most of the interstation distances exceed the influence ranges. Our study concludes that the influence range of the design storm depth is dependent on the design duration and recurrence interval and is a key factor in developing design storm contours. Copyright © 2003 John Wiley & Sons, Ltd.
Determining long time‐scale hyporheic zone flow paths in Antarctic streams
Authors: Gooseff Michael N. , McKnight Diane M. , Runkel Robert L. , Vaughn Bruce H.
Published: June 2003

In the McMurdo Dry Valleys of Antarctica, glaciers are the source of meltwater during the austral summer, and the streams and adjacent hyporheic zones constitute the entire physical watershed; there are no hillslope processes in these systems. Hyporheic zones can extend several metres from each side of the stream, and are up to 70 cm deep, corresponding to a lateral cross‐section as large as 12 m2, and water resides in the subsurface year around. In this study, we differentiate between the near‐stream hyporheic zone, which can be characterized with stream tracer experiments, and the extended hyporheic zone, which has a longer time‐scale of exchange. We sampled stream water from Green Creek and from the adjacent saturated alluvium for stable isotopes of D and 18O to assess the significance and extent of stream‐water exchange between the streams and extended hyporheic zones over long time‐scales (days to weeks). Our results show that water residing in the extended hyporheic zone is much more isotopically enriched (up to 11‰ D and 2·2‰ 18O) than stream water. This result suggests a long residence time within the extended hyporheic zone, during which fractionation has occurred owing to summer evaporation and winter sublimation of hyporheic water. We found less enriched water in the extended hyporheic zone later in the flow season, suggesting that stream water may be exchanged into and out of this zone, on the time‐scale of weeks to months. The transient storage model OTIS was used to characterize the exchange of stream water with the extended hyporheic zone. Model results yield exchange rates (α) generally an order magnitude lower (10−5 s−1) than those determined using stream‐tracer techniques on the same stream. In light of previous studies in these streams, these results suggest that the hyporheic zones in Antarctic streams have near‐stream zones of rapid stream‐water exchange, where ‘fast’ biogeochemical reactions may influence water chemistry, and extended hyporheic zones, in which slower biogeochemical reaction rates may affect stream‐water chemistry at longer time‐scales. Copyright © 2003 John Wiley & Sons, Ltd.
Development of a remotely controlled debris flow monitoring system in the Dolomites (Acquabona, Italy)
Authors: Tecca Pia R. , Galgaro Antonio , Genevois Rinaldo , Deganutti Andrea M.
Published: June 2003

Direct measurements of the hydrological conditions for the occurrence of debris flows and of flow behaviour are of the outmost importance for developing effective flow prevention techniques. An automated and remotely controlled monitoring system was installed in Acquabona Creek in the Dolomites, Italian Eastern Alps, where debris flows occur every year. Its present configuration consists of three on‐site stations, located in the debris‐flow initiation area, in the lower channel and in the retention basin. The monitoring system is equipped with sensors for measuring rainfall, pore‐water pressure in the mobile channel bottom, ground vibrations, debris flow depth, total normal stress and fluid pore‐pressure at the base of the flow. Three video cameras take motion pictures of the events at the initiation zone, in the lower channel and in the deposition area. Data from the on‐site stations are radio‐transmitted to an off‐site station and stored in a host PC, from where they are telemetrically downloaded and used by the Padova University for the study of debris flows. The efficiency of the sensors and of the whole monitoring system has been verified by the analysis of data collected so far. Examples of these data are presented and briefly discussed. If implemented at the numerous debris‐flow sites in the Dolomitic Region, the technology used, derived from the development of this system, will provide civil defence and warn residents of impending debris flows. Copyright © 2003 John Wiley & Sons, Ltd.
Near‐infrared spectroscopy of a hydroecological indicator: new tool for determining sustainable yield for Floridan aquifer system
Authors: Bacchus Sydney T. , Archibald Douglas D. , Brook George A. , Britton Kerry O. , Haines Bruce L. , Rathbun Stephen L. , Madden Marguerite
Published: June 2003

Pond‐cypress (Taxodium ascendens Brong.) is a dominant canopy species in depressional wetlands of the south‐eastern Coastal Plain. Unsustainable withdrawals from the karst Floridan aquifer system have caused premature decline and death of pond‐cypress trees, presumably owing to altered hydroperiods (which alter the flow of water and nutrients in trees). There has been no scientifically based means to determine sustainable yield from this regional aquifer system or to detect early stages of physical/ecological damage associated with groundwater mining and aquifer storage and recovery (ASR, which also can alter natural hydroperiods). In this study, the relationship between visual symptoms (indicators) of stress or premature decline, and spectral reflectance was evaluated using dried, milled branch tips collected from natural stands of mature pond‐cypress. Depressional systems evaluated represented four of the six aquifer system subregions where subsurface perturbations from groundwater mining: (i) were presumed not to be occurring (reference wetlands); (ii) may be occurring but are not documented; and (iii) have been confirmed. Sampled trees were assigned to one of three stress classes (1, no/minimal; 2, moderate; 3, severe) based on the visual indicators. Partial least squares–linear discriminant analysis of second derivative spectral transformations in the visible/shortwave near‐infrared (NIR) region (400–1100 nm) and the NIR region (1100–2500 nm) was used to evaluate the samples in assigned classes.

Class 1 samples were discriminated from combined class 2 and 3 samples in the NIR region with 100% and 97% accuracy for consecutive winter sample periods (before bud‐break). The percentage of correctly classified samples in this spectral region was lower (85%) for summer samples (full leaf‐out). Second‐derivative models for the NIR region developed from the winter data sets predicted assigned classes for alternate winter's samples with an accuracy of 97% and 100%. High correlation between spectral reflectance of dried, milled branch tips collected from mature pond‐cypress in winter and visual indicators of premature decline suggests in situ pond‐cypress are hydroecological indicators of anthropogenic subsurface hydroperiod perturbations. This approach provides objective means for early detection of unsustainable aquifer yield and adverse impacts from ASR activities in the south‐eastern Coastal Plain. Used in conjunction with hydrological monitoring and modelling, the hydroecological indicators should provide the means with which sustainable yield in the south‐eastern Coastal Plain can be achieved and maintained. Copyright © 2003 John Wiley & Sons, Ltd.
Hydraulic conditions, oxygenation, temperatures and sediment relationships of bedwork watermeadows
Authors: Cutting Roger L. , Cook Hadrian F. , Cummings Ian P. F.
Published: June 2003

This study investigates the interactions of water, oxygen, temperature, suspended sediment and topsoil texture of bedwork watermeadows. These ancient grassland irrigation systems survive on the floodplain around Salisbury, England but recent interest in their conservation and rehabilitation is not matched by detailed understanding of their operation. The dominant ‘bedwork’ form, by which water runs along the top of ridges and down ‘panes’, enables water to move swiftly through the sward and drain to avoid stagnation. This investigation demonstrates that condition of surface flow and rates of infiltration encourage the solution of atmospheric oxygen in the water, offsetting potentially anaerobic conditions in the root zone. Temperature conditions imparted by the flow were measured and found to be conducive to the early growth of grass. Whereas the sediment budget was found to be conservative under a steady‐state hydraulic regime, there is substantial ingress of suspended sediment at the start of an irrigation event and the sward traps coarse to medium‐sized silt particle fractions and influences topsoil texture. It is concluded that a study of watermeadow operation permits insights into the operation of floodplain processes in general. Copyright © 2003 John Wiley & Sons, Ltd.
Sediment yield modelling for small agricultural catchments: land‐cover parameterization based on remote sensing data analysis
Authors: Paringit Enrico C. , Nadaoka Kazuo
Published: June 2003

Vegetation and soil properties and their associated changes through time and space affect the various stages of soil erosion. The island of Ishigaki in Okinawa Prefecture, Japan is of particular concern because of the propensity of the red‐soil‐dominated watersheds in the area to contribute substantial sediment discharge to adjacent coastal areas. This paper discusses the application of remote sensing techniques in the retrieval of vegetation and soil parameters necessary for the distributed soil‐loss modelling in small agricultural catchments and analyses the variation in erosional patterns and sediment distribution during rainfall events using numerical solutions of overland flow simulations and sediment continuity equations. To account for the spatial as well as temporal variability of selected parameters of the soil‐loss equations, a method is proposed to account for the variability of associated vegetation cover based on their spectral characteristics as captured by remotely sensed data. To allow for complete spatial integration, modelling the movement of sediment is accomplished under a loose‐coupled GIS computational framework. This study lends a theoretical support and empirical evidence to the role of vegetation as a potential agent for soil erosion control. Copyright © 2003 John Wiley & Sons, Ltd.
Floodplain friction parameterization in two‐dimensional river flood models using vegetation heights derived from airborne scanning laser altimetry
Authors: Mason David C. , Cobby David M. , Horritt Matthew S. , Bates Paul D.
Published: June 2003

Two‐dimensional (2‐D) hydraulic models are currently at the forefront of research into river flood inundation prediction. Airborne scanning laser altimetry is an important new data source that can provide such models with spatially distributed floodplain topography together with vegetation heights for parameterization of model friction. The paper investigates how vegetation height data can be used to realize the currently unexploited potential of 2‐D flood models to specify a friction factor at each node of the finite element model mesh. The only vegetation attribute required in the estimation of floodplain node friction factors is vegetation height. Different sets of flow resistance equations are used to model channel sediment, short vegetation, and tall and intermediate vegetation. The scheme was tested in a modelling study of a flood event that occurred on the River Severn, UK, in October 1998. A synthetic aperture radar image acquired during the flood provided an observed flood extent against which to validate the predicted extent. The modelled flood extent using variable friction was found to agree with the observed extent almost everywhere within the model domain. The variable‐friction model has the considerable advantage that it makes unnecessary the unphysical fitting of floodplain and channel friction factors required in the traditional approach to model calibration. Copyright © 2003 John Wiley & Sons, Ltd.
The inhibitory activity of serum to prevent bacterial adhesion is mainly due to apo‐transferrin
Authors: Ardehali Reza , Shi Lei , Janatova Jarmila , Mohammad S. Fazal , Burns Gregory L.
Published: June 2003

A marked, up to 5‐fold, reduction in bacterial adhesion to Tecoflex® polyurethane (PU) surfaces was observed in the presence of bovine/human serum or plasma at 0.5% or higher concentrations in the medium. Further investigation of the phenomenon resulted in identification, isolation, and characterization of the serum component with the ability to significantly reduce bacterial adhesion. Upon fractionation of bovine serum by an anion exchange chromatography, protein pools were made and analyzed by immunoelectrophoresis and by polyacrylamide gel electrophoresis in the presence of SDS and were examined for their effect on the adhesion of Staphylococcus epidermidis to PU surfaces. The pool exhibiting a significant inhibitory effect was subjected to further biochemical tests, which resulted in the identification of transferrin (Tf) as its predominant protein. Bacterial adhesion studies in the presence of purified Tf revealed that holo‐Tf (iron‐containing form) had no influence on bacterial adhesion at any concentration. Only apo‐Tf (iron‐lacking form) exerted the inhibitory effect, in a dose responsive manner at concentrations of 10 μg/mL or higher. Bacteria remained viable when suspended at the low apo‐Tf concentrations, sufficient to prevent bacterial adhesion. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 21–28, 2003
Elastic biodegradable poly(glycolide‐co‐caprolactone) scaffold for tissue engineering
Authors: Lee Soo‐Hong , Kim Byung‐Soo , Kim Soo Hyun , Choi Sung Won , Jeong Sung In , Kwon Il Keun , Kang Sun Woong , Nikolovski Janeta , Mooney David J. , Han Yang‐Kyoo , Kim Young Ha
Published: June 2003

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, and it would be necessary for the development of the elastic scaffolds if one wishes to engineer SM tissues under cyclic mechanical loading. This study reports on the development of an elastic scaffold fabricated from a biodegradable polymer. Biodegradable poly(glycolide‐co‐caprolactone) (PGCL) copolymer was synthesized from glycolide and ϵ‐caprolactone in the presence of stannous octoate as catalyst. The copolymer was characterized by 1H‐NMR, gel permeation chromatography and differential scanning calorimetry. Scaffolds for tissue engineering applications were fabricated from PGCL copolymer using the solvent‐casting and particle‐leaching technique. The PGCL scaffolds produced in this fashion had open pore structures (average pore size = 250 μm) without the usual nonporous skin layer on external surfaces. Mechanical testing revealed that PGCL scaffolds were far more elastic than poly(lactic‐co‐glycolic acid) (PLGA) scaffolds fabricated using the same method. Tensile mechanical tests indicated that PGCL scaffolds could withstand an extension of 250% without cracking, which was much higher than withstood by PLGA scaffolds (10–15%). In addition, PGCL scaffolds achieved recoveries exceeding 96% at applied extensions of up to 230%, whereas PLGA scaffolds failed (cracked) at an applied strain of 20%. Dynamic mechanical tests showed that the permanent deformation of the PGCL scaffolds in a dry condition produced was less than 4% of the applied strain, when an elongation of 20% at a frequency of 1 Hz (1 cycle per second) was applied for 6 days. Moreover, PGCL scaffolds in a buffer solution also had permanent deformations less than 5% of the applied strain when an elongation of 10% at a frequency of 1 Hz was applied for 2 days. The usefulness of the PGCL scaffolds was demonstrated by engineering SM tissues in vivo. This study shows that the elastic PGCL scaffolds produced in this study could be used to engineer SM‐containing tissues (e.g. blood vessels and bladders) in mechanically dynamic environments. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 29–37, 2003
Surface modification of PLGA microspheres
Authors: Müller M. , Vörös J. , Csúcs G. , Walter E. , Danuser G. , Merkle H. P. , Spencer N. D. , Textor M.
Published: June 2003

Microspheres made of poly(lactic‐co‐glycolic acid) (PLGA) are biocompatible and biodegradable, rendering them a promising tool in the context of drug delivery. However, nonspecific adsorption of plasma proteins on PLGA micro‐ and nanospheres is a main limitation of drug targeting. Poly(L‐lysine)‐g‐poly(ethylene glycol) (PLL‐g‐PEG), physisorbed on flat metal oxide surfaces, has previously been shown to suppress protein adsorption drastically. The goal of our work was to characterize the efficiency of the protein repellent character of PLL‐g‐PEG on PLGA microspheres and to show the feasibility of introducing functional groups on the PLGA microspheres via functionalized PLL‐g‐PEG. To quantify the adsorbed amount of protein, a semiquantitative method that uses confocal laser scanning microscopy (CLSM) was applied. The first part of the experiment confirms the feasibility of introducing specific functional groups on PLL‐g‐PEG–coated PLGA microspheres. In the second part of the experiment, PLL‐g‐PEG–coated PLGA microspheres show a drastic decrease of adsorbed proteins by two orders of magnitude in comparison to uncoated PLGA microspheres. Low protein‐binding, functionalizable microspheres provide a fundamental basis for the design of drug delivery and biosensor systems. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 55–61, 2003
Noninvasive bone replacement with a new injectable calcium phosphate biomaterial
Authors: Gauthier O. , Khairoun I. , Bosco J. , Obadia L. , Bourges X. , Rau C. , Magne D. , Bouler J. M. , Aguado E. , Daculsi G. , Weiss P.
Published: June 2003

The use of injectable calcium phosphate (CaP) biomaterials in noninvasive surgery should provide efficient bone colonization and implantation. Two different kinds of injectable biomaterials are presently under development: ionic hydraulic bone cements that harden in vivo after injection, and an association of biphasic calcium phosphate (BCP) ceramic granules and a water‐soluble polymer vehicle (a technique particularly investigated by our group), providing an injectable CaP bone substitute (IBS). In our study, we compared these two approaches, using physicochemical characterizations and in vivo evaluations in light microscopy, scanning electron microscopy, and three‐dimensional microtomography with synchrotron technology. Three weeks after implantation in rabbit bone, both biomaterials showed perfect biocompatibility and bioactivity, but new bone formation and degradation of the biomaterial were significantly greater for BCP granules than for ionic cement. Newly formed bone developed, binding the BCP granules together, whereas new bone grew only on the surface of the cement, which remained dense, with no obvious degradation 3 weeks after implantation. This study confirms that BCP granules carried by a cellulosic polymer conserve bioactivity and are conducive to earlier and more extensive bone substitution than a carbonated‐hydroxyapatite bone cement. The presence of intergranular spaces in the BCP preparation, as shown on microtomography imaging, seems particularly favorable, allowing body fluids to reach each BCP granule immediately after implantation. Thus, the IBS functions as a completely interconnected ceramic with total open macroporosity. This new bone replacement approach should facilitate microinvasive bone surgery and local delivery of bone therapy agents. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 47–54, 2003
Osteogenic enrichment of bone‐marrow stromal cells with the use of flow chamber and type I collagen‐coated surface
Authors: Lan Cheng‐Wen , Wang Fung Fang , Wang Yng Jiin
Published: June 2003

The stromal cells of the bone marrow are able to attach to the surface and differentiate into cells with bone‐forming capability when stimulated with osteogenic supplements. In this study, we have employed a flow‐chamber device containing a collagen‐coated surface to enrich the potential osteoprogenitor cells from bone marrow stromal cells (BMSCs). The population of the cells attached to the collagen‐coated substratum is about twice that attached to the uncoated surface. In the flow chamber, almost all marrow cells attached on the untreated glass were flushed out at the shear stress of 1.10 dyne/cm2. On the other hand, 25% of the marrow cells remained attached to the collagen‐coated glass, even under the shear stress of 1.30 dyne/cm2. The collagen‐attached marrow cells exhibited similar, specific alkaline phosphatase activity compared with that of the cells attached to the uncoated dish in the early stage of culturing. Nevertheless, only the collagen‐attached marrow cells later expressed significant amounts of osteocalcin, which is a specific marker for osteoblast cells. Thus, we have successfully developed a protocol that uses a collagen‐coated surface efficiently in a flow chamber to enrich the osteogenic cells from the BMSCs. This provides a useful tool to obtain osteogenic cells from bone marrow for biologic and clinical applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 38–46, 2003
Monocyte/macrophage interactions with base and linear‐ and star‐like PEG‐modified PEG‐poly(acrylic acid) co‐polymers
Authors: Wagner Victoria E. , Bryers James D.
Published: June 2003

Poly(ethylene glycol):poly(acrylate) PEG‐g‐PA co‐polymers were made that inhibited nonspecific protein and cellular adhesion. PEG‐g‐PA co‐polymers were then covalently modified with either cell adhesion peptides or fragments of antibodies to monocyte/macrophage integrin receptors (anti‐VLA4, anti‐β1, anti‐β2, and anti‐CD64) known to enhance macrophage adhesion and, perhaps, modulate their activation. Peptides were either directly conjugated to the base material or linked by way of PEO‐star tethers. Fragments of the antibody region containing the antigen‐binding site (Fab′ fragments) were coupled to other PEG‐g‐PA samples using the sulhydryl end groups on Fab′ fragments to amine‐bearing PEO stars. Macrophage adhesion rates, phagocytic response (oxidative burst), and cytokine expression were determined for each PEG‐g‐PA material. Luminol‐enhanced chemiluminescence was used as a semiquantitative indication of monocyte‐macrophage phagocytic activation (oxidative burst). Macrophage cytokine expression in response to control, base, and modified materials was determined by ELISAs for TNF‐α, IL‐1β, IL‐6, and IL‐8. Tissue culture poly(styrene) (TCPS)‐mediated the greatest number of adherent monocyte/macrophage cells relative to PEG‐g‐PA materials. Both YRGDS and YEILDV peptides, whether directly or indirectly (via StarPEO) conjugated to PEG‐g‐PA, increased adhesion versus controls. Fab′ fragments of all four antibodies also promoted enhanced adhesion versus controls. Fab′StarPEO materials presented two orders of magnitude fewer ligands per surface unit area than peptide star materials (108 vs. 1010), but were able to adhere similar numbers of cells. For surfaces presenting Fab′VLA‐4 or YEILDV, both of which may both bind to a cell's VLA‐4 receptor, the Star:VLA4 surface showed a greater number of adherent monocyte/macrophages. This result suggests that the Fab′ had a higher affinity to the cell receptor than a corresponding minimal peptide binding sequence. All materials exhibited low oxidative burst (luminescence counts per minute, LCPM) per cell DNA without the addition of exogenous stimuli (LCPM/DNA < 100). Directly conjugated peptide materials, poly(propylene) (PP), and TCPS showed the lowest levels of LCPM/DNA without the addition of exogenous stimulus (LCPM/DNA < 20). There was no correlation between LCPM/DNA ratios, with and without added LPS stimulus, versus the individual substrates. Monocyte/macrophages adherent to TCPS substrata showed the overall highest stimulatory potential in cytokine expression response to exogenous LPS, followed by PP > PEG‐g‐PA > StarPEO. Cells adherent to peptide‐modified materials and Fab′‐modified materials were overall less stimulated. The method of presenting the peptides (i.e., directly or via Star PEO) influenced the level of cytokine secreted by the adherent macrophage. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 62–78, 2003
Biomimetic nano‐apatite coating capable of promoting bone ingrowth
Authors: Li Panjian
Published: June 2003

Nano‐apatite coating closely mimicking bone mineral was grown directly on titanium soaked in an aqueous solution containing all major inorganic components present in the body, mainly, HCO, Ca2+, HPO, and Mg2+ ions. The removal of HCO3− ions from the solution in the form of CO2 resulted in the increase of solution pH. As a consequence of this reaction, the nano‐apatite coating was formed on the surface of titanium with composition and structure equivalent to those of bone mineral. The biomimetic nano‐apatite was demonstrated to be capable of conducting bone formation and promoting direct bone apposition. This bioactive coating also affected the behavior of human osteoblasts as indicated by their morphologies observed in cell culture study. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 79–85, 2003
In vivo biocompatibility evaluation of cellulose macrocapsules for islet immunoisolation: Implications of low molecular weight cut‐off
Authors: Risbud Makarand V. , Bhargava Shobha , Bhonde Ramesh R.
Published: June 2003

Earlier we showed the in vitro suitability of cellulose molecular dialysis membrane of low cut‐off for islet immunoisolation. Using a syngenic islet transplantation model, here we report the in vivo biocompatibility status and discuss implications of the low molecular weight cut‐off of this membrane. Streptozotocin diabetic mice were transplanted ip with islet grafts in cellulose macrocapsules and monitored for 6 weeks for their blood glucose profiles. Membrane biocompatibility was evaluated by assessing islet graft morphometry, viability, functionality, and tissue reaction against the capsules. Animals (n = 10) attained normoglycemia after 1 week of transplantation and remained nondiabetic throughout a follow‐up of 6 weeks. Animals subjected to a glucose tolerance test at the end of the study showed delayed glycemic control, indicating a delayed insulin response. Grafts retrieved after the 15th day and after 6 weeks showed viable islets, between 70–80% and ≈40%, respectively, with morphometric parameters similar to freshly isolated islets. Graft retrievals resulted in a recurrence of hyperglycemia, indicating a functional tissue mass. A mild tissue reaction with a few immunocytes and a very thin fibrous capsular reaction were seen against the macrocapsule membrane. This study points out the in vivo suitability of cellulose membrane for islet immunoisolation. However, applicability of this membrane is limited due to its low cut‐off value. Membranes with a higher molecular weight cut‐off may render better glycemic control and higher graft viability. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 86–92, 2003
Bioactivity of gel–glass powders in the CaO‐SiO2 system: A comparison with ternary (CaO‐P2P5‐SiO2) and quaternary glasses (SiO2‐CaO‐P2O5‐Na2O)
Authors: Saravanapavan Priya , Jones Julian R. , Pryce Russell S. , Hench Larry L.
Published: June 2003

Bioactive glasses react chemically with body fluids in a manner that is compatible with the repair processes of the tissues. This results in the formation of an interfacial bond between the glasses and living tissue. Bioactive glasses also stimulate bone–cell proliferation. This behavior is dependent on the chemical composition as well as the surface texture of the glasses. It has been recently reported that gel‐derived monolith specimens in the binary SiO2 CaO are bioactive over a similar molar range of SiO2 content as the previously studied ternary CaO‐P2O5‐SiO2 system. In this report, the preparation and bioactivity of the binary gel–glass powder with 70 mol % SiO2 is discussed and its bioactivity is compared with the melt‐derived 45S5 (quaternary) Bioglass® and sol–gel‐derived 58S (ternary) bioactive gel–glass compositions. Dissolution kinetic parameters K1 and K2 were also computed based on the silicon release for all glass powders. It was shown that the simple two‐component SiO2‐CaO gel–glass powder is bioactive with comparable dissolution rates as the clinically used melt‐derived 45S5 Bioglass® powder and extensively studied sol–gel‐derived 58S gel–glass powder. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 110–119, 2003
In vivo degradation characteristics of poly(glycerol sebacate)
Authors: Wang Yadong , Kim Yu Mi , Langer Robert
Published: June 2003

We have developed a series of biodegradable elastomers, poly(glycerol sebacate) (PGS), based on glycerol and sebacic acid. The polymers are potentially useful in soft tissue regeneration and engineering. To evaluate the performance of PGS in a physiological environment, we compared their degradation profiles with poly(DL‐lactide‐co‐glycolide) (50:50, carboxyl ended, Mw 15,000) in vivo. Among the parameters examined are changes in weight and mechanical strength with time, implant geometry, surface characteristics, and degree of swelling. Unlike poly(DL‐lactide‐co‐glycolide), PGS primarily degrades by surface erosion, which gives a linear degradation profile of mass, preservation of geometry and intact surface, and retention of mechanical strength. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 192–197, 2003
Fatigue crack propagation path across the dentinoenamel junction complex in human teeth
Authors: Dong X. D. , Ruse N. D.
Published: June 2003

The human tooth structures should be understood clearly to improve clinically used restorative materials. The dentinoenamel junction (DEJ) plays a key role in resisting crack propagation in teeth. The aim of this study was to determine the fracture toughness of the enamel‐DEJ‐dentin complex and to investigate the influence of the DEJ on the fatigue crack propagation path across it by characterizing fatigue‐fractured enamel‐DEJ‐dentin complexes using optical and scanning electron microscopy. The results of this study showed that the fracture toughness of the enamel‐DEJ‐dentin complex was 1.50 ± 0.28 Mpa·m1/2. Based on the results of this investigation, it was concluded that the DEJ complex played a critical role in resisting crack propagation from enamel into dentin. The DEJ complex is, approximately, a 100 to 150 μm broad region at the interface between enamel and dentin. The toughening mechanism of the DEJ complex may be explained by the fact that crack paths were deflected as cracks propagated across it. Understanding the mechanism of crack deflection could help in improving dentin‐composite as well as ceramic‐cement interfacial qualities with the aim to decrease the risk of clinical failure of restorations. Both can be viewed as being composed from a layer of material of high strength and hardness bonded to a softer but tougher substratum (dentin). The bonding agent or the luting cement layer may play the critical role of the DEJ in improving the strength of these restorations in clinical situations. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 103–109, 2003
Role of elastin in pathologic calcification of xenograft heart valves
Authors: Bailey Michael T. , Pillarisetti Swadeep , Xiao Hui , Vyavahare Naren R.
Published: June 2003

Bioprosthetic heart valves fabricated from glutaraldehyde crosslinked porcine aortic valves often fail because of calcific degeneration. Calcification occurs in both cusp and aortic wall portions of bioprosthetic heart valves. The purpose of this study was to discern the role of different aortic wall components in the calcification process. Thus, we selectively extracted cells and other extracellular matrix proteins from porcine aorta using trypsin/DNase/RNase, cyanogen bromide (CNBr), and sodium hydroxide (NaOH) treatments and subdermally implanted these pretreated aortas in young rats. Total DNA and phospholipid data showed complete removal of cells by CNBr and NaOH treatments, whereas trypsin/DNase/RNase treatment was effective in removing DNA but not phospholipids. As shown by amino acid data and Masson's trichrome staining, collagen was removed in CNBr and NaOH treatments. Control fresh porcine aorta calcified significantly after 21 days of implantation (Ca 26.4 ± 2.4 μg/mg). Removal of cells and collagen from the aorta by CNBr treatment did not lead to a statistically significant reduction in aortic calcification (Ca 20.8 ± 3.0 μg/mg). Moreover, partial degradation of elastin fibers caused by NaOH (during extraction) and trypsin treatment (after implantation) of the aorta significantly increased elastin‐oriented calcification (Ca 94.4 ± 9.3 and 58.4 ± 4.6 μg/mg, respectively). Our results indicate that the elastin component of the aorta may undergo independent calcification irrespective of devitalized cell‐mediated calcification observed in glutaraldehyde crosslinked aortas. Our results also demonstrate the importance of studying elastin‐oriented calcification in decellularized elastin‐rich aortic matrices currently used in tissue‐engineering applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 93–102, 2003
In vitro fracture toughness of human dentin
Authors: Imbeni V. , Nalla R. K. , Bosi C. , Kinney J. H. , Ritchie R. O.
Published: June 2003

The in vitro fracture toughness of human dentin has been reported to be of the order of 3 MPa√m. This result, however, is based on a single study for a single orientation, and furthermore involves notched, rather than fatigue precracked, test samples. The present study seeks to obtain an improved, lower‐bound, value of the toughness, and to show that previously reported values may be erroneously high because of the absence of a sharp crack as the stress concentrator. Specifically, the average measured critical stress intensity, Kc, for the onset of unstable fracture along an orientation perpendicular to the long axis of the tubules in dentin is found to be 1.8 MPa√m in simulated body fluid (Hanks' balanced salt solution), when tested in a three‐point bending specimen containing a (nominally) atomically sharp precrack generated during prior fatigue cycling. This is to be compared with a value of 2.7 MPa√m measured under identical experimental conditions except that the bend specimen contained a sharp machined notch (of root radius 30–50 μm). The effect of acuity of the precrack on the fracture toughness of human dentin is discussed in the context of these data. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 1–9, 2003
Biocompatibility and hemocompatibility of surface‐modified NiTi alloys
Authors: Armitage David A. , Parker Terry L. , Grant David M.
Published: June 2003

Nickel titanium (NiTi) shape memory alloys have been investigated for several years with regard to biomedical applications. However, little is known about the influences of surface modifications on the biocompatibility of these alloys. The effects of a range of surface treatments were investigated. Cytotoxicity and cytocompatibility studies with both fibroblast and endothelial cells showed no differences in the biocompatibility of any of the NiTi surfaces. The cytotoxicity and cytocompatibility of all surfaces were favorable compared to the controls. The hemolysis caused by a range of NiTi surfaces was no different from that caused by polished 316L stainless steel or polished titanium surfaces. The spreading of platelets has been linked to the thrombogenicity of materials. Platelet studies here showed a significant increase in thrombogenicity on polished NiTi surfaces compared to 316L stainless steel and pure titanium surfaces. Heat treatment of NiTi was found to significantly reduce thrombogenicity, to the level of the control. The XPS results showed a significant decrease in the concentration of surface nickel with heat treatment and changes in the surface nickel itself from a metallic to an oxide state. This correlates with the observed reduction in thrombogenicity. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 129–137, 2003