bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix metalloproteinase‐9 interplays with the IGFBP2–IGFII complex to promote cell growth and motility in astrocytomas
Authors: Rorive Sandrine , Berton Alix , D'haene Nicky , Takacs Constantin Nicolae , Debeir Olivier , Decaestecker Christine , Salmon Isabelle
Published: June 2008

Insulin‐like growth factor II (IGFII) acts as a potent mitogen for several tumor types and has been reported to positively influence astrocytoma cell growth and motility. In the central nervous system, IGFII bioavailability is mainly modulated by insulin‐like growth factor binding protein 2 (IGFBP2), which sequestrates IGFII and therefore prevents its interaction with the type‐1 IGF receptor (IGF‐IR). Proteolysis of IGFBP2 is the predominant mechanism recognized to reduce the binding affinity of IGFBP2 for IGFII, thus favoring dissociation of IGFII from the IGFBP2–IGFII complex. It is known that certain proteases involved in astrocytoma malignancy, such as matrix metalloproteinase‐7 (MMP‐7), plasmin, and cathepsin D, are able to proteolyze IGFBP2 in vitro. The present study aims to investigate whether other proteases expressed by astrocytomas, specifically MMP‐2, MMP‐9, and membrane‐type 1 matrix metalloprotease (MT1‐MMP), are able to proteolyze the IGFBP2–IGFII complex. Our results show the following: (i) MMP‐9 proteolyzes the IGFBP2–IGFII complex in vitro, while MMP‐2 and MT1‐MMP do not; (ii) this MMP‐9‐induced IGFBP2–IGFII complex proteolysis releases free IGFII, which contributes to enhance the motility and the growth of LN229 astrocytoma cells. Furthermore, this study also highlights that the formation of the IGFBP2–IGFII complex inhibits IGFBP2's cell motility promoting effect by reducing the pool of free IGFBP2. In conclusion, MMP‐9‐induced IGFBP2 proteolysis may be regarded as an important post‐translational event involved in astrocytoma aggressiveness. These new findings support drug targeting of MMP‐9 as an interesting approach in the treatment of astrocytoma. © 2008 Wiley‐Liss, Inc.
The expression of tubulin polymerization promoting protein TPPP/p25α is developmentally regulated in cultured rat brain oligodendrocytes and affected by proteolytic stress
Authors: Goldbaum Olaf , Jensen Poul Henning , Richter‐Landsberg Christiane
Published: June 2008

The tubulin polymerization‐promoting protein (TPPP)/p25α was identified as a brain specific protein, is associated with microtubules (MTs) in vitro and can promote abnormal MT assembly. Furthermore it has aggregation promoting properties and is a constituent in pathological protein deposits of neurodegenerative diseases. In the brain, TPPP/p25α is present in myelinating oligodendrocytes. Here we show, using cultured rat brain oligodendrocytes, that TPPP/p25α expression is increasing during development in culture, and particularly in immature cells is associated with the centrosome. MT binding properties in oligodendrocytes are rather low, however, when MTs are disassembled by nocodazole, TPPP/p25α accumulates in the perinuclear region. Treatment of oligodendrocytes with the proteasomal inhibitor MG‐132 (1 μM; 18 h) caused an increase in the amount of TPPP/p25α by about 40%, a decrease in its solubility, and led to the appearance of TPPP/p25α‐positive cytoplasmic inclusions, which stained with thioflavin S and resembled inclusion bodies. Hence, it might be speculated that acute or chronic malfunction of the proteasomal degradation system, leading to the accumulation of aggregation prone proteins and the pro‐aggregatory protein TPPP/p25α or to the aggregation of TPPP/p25α on its own, is causally related to the protein aggregation process in a variety of neurodegenerative diseases. © 2008 Wiley‐Liss, Inc.
Drought impacts on Canadian prairie wetland snow hydrology
Authors: Fang X. , Pomeroy J. W.
Published: June 2008

Droughts affect the Canadian prairies on a regular basis. The drought of 1999–2005 was the most recent one and was the most severe on record for part of the region. It was characterized by lack of precipitation, desiccation of agricultural soils, decline in groundwater tables and depletion of surface water supplies. The effects on wetlands were particularly severe, with many wetlands completely drying out. The physically based cold regions hydrological modelling (CRHM) platform was used to analyse the impacts of this recent drought on water flow to and storage within a small Canadian prairie wetland. Model simulations were conducted for a small closed basin for the drought period of 1999–2005 and the relatively wet period of 2005–2006. The basin consists of a cultivated upland, draining into a glacially formed pothole depression with no outlet. The wetland fills the depression in wet years and is underlain by a heavy glacial till that impedes groundwater exchange. Results from the observations and model outputs showed that much lower precipitation and snow accumulation, shorter snow‐covered duration, enhanced winter evaporation, and much lower discharge to the wetland from basin snowmelt runoff developed in the severe drought years of 1999–2002. As a result, there were only 14·9, 3·7, and 14·4 mm of snowmelt runoff for the springs of 2000, 2001, and 2002, respectively. Compared to the 68·2 mm of melt‐water discharge in the spring of 2006, discharge to the wetland was 78, 95, and 79% less for these years. This is consistent with the observed water level in the wetland, which shows dramatic decline over this period. CRHM was used to investigate the potential impact of snow management as a tool to enhance runoff to the wetland during droughts. Model runs parameterized with suppressed vegetation in the cultivated land surrounding the wetland showed increased blowing snow transport to the wetland from an area exceeding the basin area that resulted in greater snow accumulation in and melt‐water supply to the wetland. Copyright © 2008 John Wiley & Sons, Ltd.
Impacts of nutrient management and decrease in paddy field area on groundwater nitrate concentration: a case study at the Nasunogahara alluvial fan, Tochigi Prefecture, Japan
Authors: Somura Hiroaki , Goto Akira , Matsui Hiroyuki , Ali Musa Elhassan
Published: June 2008

In order to help evaluate the trends in the NO3‐N concentration in groundwater with a view to preventing further degradation in water quality in the future, a distributed groundwater quality model was constructed for the Nasunogahara basin. The best fit for the groundwater table elevations by the flow component of the model was achieved with average mean absolute errors (MAEs) of 0·92 m for the calibration period and 0·83 m for the validation period. Moreover, the best fit for the NO3‐N concentration by the water quality component was achieved with average mean relative errors (MREs) of 29·8% for the calibration period and 30·3% for the validation period. After developing a robust model, various change scenarios were tested; specifically, the effects of effluent load control and a decrease in paddy field area on the NO3‐N concentration in groundwater were predicted. The most intensively farmed area contributed about 40% of the total effluent load because of livestock farming in the basin. When the effluent load from this area was decreased by 50%, the average NO3‐N concentrations at sites S1, S2 and S3 were reduced by about 15%; however, the average concentrations at S4 and S5 were reduced by only 1%. Furthermore, when the total effluent load from the concentrated livestock area was removed completely, the average groundwater NO3‐N concentrations at S1, S2 and S3 were reduced by about 30% as compared with the original calculated results. In contrast, decreasing the area of the paddy fields in the basin did not greatly influence the groundwater NO3‐N concentration. In the case of a 70% reduction in paddy field area, average NO3‐N concentrations increased by about 7% at S1, S2 and S3. Copyright © 2008 John Wiley & Sons, Ltd.
Early findings in comparison of AMSR‐E/Aqua L3 global snow water equivalent EASE‐grids data within situobservations for Eastern Turkey
Authors: Tekeli A. Emre
Published: June 2008

Microwave remote sensing (RS) enables the direct determination of snow water equivalent (SWE), which is an important snow parameter for water resources management. The accuracy of remotely sensed SWE values has always been a concern. Previous studies evaluated global SWE monitoring. However, regional effects such as vegetation, snow grain size, snow density and local meteorological conditions may lead to uncertainties. Thus, regional validation studies that quantify and help to understand these uncertainties and possible error sources are important both for algorithm development and accurate SWE computation.

In this study, data of Advanced Microwave Scanning Radiometer (AMSR‐E)/Aqua level 3 global SWE Equal Area Scalable Earth (EASE) Grids are compared with ground measurements for 2002–2003 winter period for Eastern Turkey, which includes the headwaters of the Euphrates and Tigris rivers and is fed largely from snowmelt. Thus, accurate determination of SWE is important in optimum resource management for both Turkey and downstream nations. Analyses indicated that AMSR‐E generally overestimated SWE in early season. As winter progressed, higherin situSWE values with respect to AMSR‐E were observed which led to underestimation by AMSR‐E. The differences between AMSR‐E andin situSWE varied between − 218 and 93 mm.

Use ofin situsnow densities lead the correlation coefficient between AMSR‐E andin situSWE to increase from 0·10 to 0·32. Underestimation of SWE by AMSR‐E occurs after some warm periods, while overestimations occur following refreezing. On rainy days or some days after precipitation within the warm periods, zero AMSR‐E SWE values are observed. Copyright © 2008 John Wiley & Sons, Ltd.
Perceptive research on wheat evapotranspiration in Pakistan
Authors: Laghari K. Q. , Lashari B. K. , Memon H. M.
Published: June 2008

The Mehran model is developed based on the FAO‐56 modified Penman–Monteith equation for computing reference and crop evapotranspiration with dual crop coefficients. Evapotranspiration (ET) of wheat in three field experiments with management‐allowed depletion (MAD) of 45, 55 and 65% was observed through gypsum block readings and a drainage lysimeter. The seasonal crop ETs were observed as 363, 359 and 332 mm, and were computed as 383, 369 and 355 mm. The corresponding water use efficiencies (WUEs) were ascertained as 14.1, 15.0 and 13.4 kg (ha mm)−1. The highest crop WUE was achieved with MAD at 55%; therefore, this research is more focused upon in the paper. The model relatively overestimated seasonal ET by 2.8%. Weekly root length and daily soil‐moisture measurements revealed that wheat extracts most of its moisture from the 0–50 cm soil profile. When practising either scientific or traditional irrigation scheduling in the country, a seasonal water amount of 370 mm is suggested for wheat to achieve optimum yield and WUE.

Statistical analysis (R2 = 0.90, T = 2.09, and F = 999) showed good correlation between computed and actual seasonal ETs of crop with an experimental MAD of 55%. The Mehran model is found to be quite versatile and can be successfully used as a decision support system (DSS) for irrigation scheduling of wheat in Pakistan. Copyright © 2008 John Wiley & Sons, Ltd.
In vivo evaluation of bonding ability and biocompatibility of a novel biodegradable glue consisting of tartaric acid derivative and human serum albumin
Authors: Iwasashi Masashi , Sakane Masataka , Saito Hirofumi , Taguchi Tetsushi , Tateishi Tetsuya , Ochiai Naoyuki
Published: June 2008

We recently developed a novel biological glue from tartaric acid derivative (TAD) with two active ester groups and human serum albumin (HSA), named TAD‐A. In this study, in vivo experiments were performed to investigate clinical applicability of TAD‐A. TAD was prepared by reacting carboxyl groups of tartaric acid with N‐hydroxysuccinimide in the presence of carbodiimide. Bonding strength was evaluated by using mouse skin closed with TAD‐A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution. Commercially available glues such as fibrin and aldehyde‐based glue were used for comparison. We found that TAD‐A's bonding strength increased significantly with TAD‐A concentration. The bonding strength of 0.5 mmol of TAD‐A in 0.8 mg of 44 w/w % HSA solution was significantly higher than that of fibrin or aldehyde‐based glue (p < 0.01), and that of 0.3 mmol of TAD‐A was significantly higher than of fibrin glue (p < 0.05). To determine toxicity, we implanted disks made from TAD‐A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution subcutaneously in mice. The inflammatory reaction in surrounding tissue increased with increasing TAD concentration, and then the disks were absorbed. In conclusion, TAD‐A has sufficient bonding strength and comparatively low toxicity in clinical use of 0.3 mmol or less of TAD and 0.8 mL of 44 w/w % HSA solution. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
pH‐dependent self‐assembling behavior of imidazole‐containing polyaspartamide derivatives
Authors: Seo Kwangwon , Kim Jong‐Duk , Kim Dukjoon
Published: June 2008

A series of pH‐sensitive polyaspartamide derivatives were prepared by grafting 1‐(3‐aminopyl)imidazole (API) and O‐(2‐aminoethyl)‐O′‐methylpolyethylene glycol (MPEG, Mw:5000), as a pH sensitive moiety and hydrophilic group, respectively. The effect of the polymer composition was examined. The UV transmittance of the polymer solutions showed a sharp pH‐dependence around pH 7 as a result of protonation or unprotonation of the imidazole rings, and a high buffering capacity between pH 5.5 and 7. Reversible pH‐dependent aggregation and deaggregation behavior was observed. The mean size of the prepared polymer aggregates with increasing degree of substitution (DS) of API ranged from 180 and 220 nm, while that of the octadecylamine‐conjugated polyaspartamide ones approximately 100 nm. The CAC of MPEG/API‐grafted polyasparamides decreased with increasing DS of API and that of the octadecylamine‐conjugated polyaspartamide aggregates increased with decreasing pH. These pH‐sensitive polyaspartamide derivatives are expected to have many applications in areas, such as an intracellular or tumor targeting drug‐delivery carrier that is triggered by very small changes in pH. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Degradation of magnesium and its alloys: Dependence on the composition of the synthetic biological media
Authors: Mueller Wolf‐Dieter , Fernández Lorenzo de Mele Monica , Nascimento Maria Lucia , Zeddies Miriam
Published: June 2008

Magnesium and its alloys are highly degradable metals that are potentially useful as biomaterials, especially in orthopaedic and cardiovascular applications. However, the in vivo corrosion has proved to be too high. Because of the complexity of in vivo conditions, a careful study of the corrosion of magnesium in synthetic solutions that simulate the in vivo environment is necessary as a first approach to predict the actual in vivo situation. The aim of this work was to evaluate the influence of the electrolyte composition on the corrosion behavior of magnesium and two Mg‐alloys in synthetic biological media. Pure magnesium and its alloys (AZ31 and LAE442) were employed in the experiments. Electrochemical potentiodynamic polarization curves were recorded in sodium chloride and PBS electrolytes with different chloride ion and albumin concentration. Optical and SEM observations complemented by EDX analysis were made. The results showed that magnesium corrosion is localized in chloride‐ and albumin‐containing buffer solutions. They also showed that the chloride concentration and the presence of buffer and protein strongly affect the electrochemical behavior of magnesium and magnesium alloys. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Chitosan nano‐/microfibrous double‐layered membrane with rolled‐up three‐dimensional structures for chondrocyte cultivation
Authors: Shim In Kyong , Suh Won Hee , Lee Sang Young , Lee Sang Hoon , Heo Seong Joo , Lee Myung Chul , Lee Seung Jin
Published: June 2008

With an aim to mimic natural extracellular matrix, we fabricated the nano‐ and microfibrous matrix with chitosan by electrospinning nanofibers onto predefined microfibrous mesh for effective chondrocytes cultivation. Rolling the double‐layered nano‐/microfibrous membranes produced three‐dimensional (3‐D) scaffolds that exhibited the interconnected open pore structure in their scanning electron microscopy images. In vitro chondrocyte culture experiment showed that this nano‐/microfibrous 3‐D matrix provided a significantly greater microenvironment for chondrocytes to proliferate and produce glycosaminoglycan as compared with only microfibrous 3‐D matrix. This difference could be explained by the result on 2‐D membrane, where chitosan nanofibrous surface substantially facilitated the cellular attachment and proliferation, and efficiently prevented phenotypic changes of chondrocytes, when compared with chitosan microfibrous membrane and film. In this regard, the nano‐/microfibrous 3‐D matrix we fabricated in this study would possess a great potential as a system for effective chondrocyte cultivation and also for application to cartilage regeneration therapy. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
A bioactive triphasic ceramic‐coated hydroxyapatite promotes proliferation and osteogenic differentiation of human bone marrow stromal cells
Authors: Nair Manitha B. , Bernhardt Anne , Lode Anja , Heinemann Christiane , Thieme Sebastian , Hanke Thomas , Varma Harikrishna , Gelinsky Michael , John Annie
Published: June 2008

Hydroxyapatite (HA) ceramics are widely used as bone graft substitutes because of their biocompatibility and osteoconductivity. However, to enhance the success of therapeutic application, many efforts are undertaken to improve the bioactivity of HA. We have developed a triphasic, silica‐containing ceramic‐coated hydroxyapatite (HASi) and evaluated its performance as a scaffold for cell‐based tissue engineering applications. Human bone marrow stromal cells (hBMSCs) were seeded on both HASi and HA scaffolds and cultured with and without osteogenic supplements for a period of 4 weeks. Cellular responses were determined in vitro in terms of cell adhesion, viability, proliferation, and osteogenic differentiation, where both materials exhibited excellent cytocompatibility. Nevertheless, an enhanced rate of cell proliferation and higher levels of both alkaline phosphatase expression and activity were observed for cells cultured on HASi with osteogenic supplements. These findings indicate that the bioactivity of HA endowed with a silica‐containing coating has definitely influenced the cellular activity, projecting HASi as a suitable candidate material for bone regenerative therapy. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Novel gene‐activated matrix with embedded chitosan/plasmid DNA nanoparticles encoding PDGF for periodontal tissue engineering
Authors: Peng Lin , Cheng Xiangrong , Zhuo Renxi , Lan Jing , Wang Yining , Shi Bin , Li Siqun
Published: June 2008

Recently, much attention has been paid to tissue engineering and local gene delivery system in periodontal tissue regeneration. Gene‐activated matrix (GAM) blends these two strategies, serving as a local bioreactor with therapeutic gene expression and providing a structural template to fill the lesion defects for cell adhesion, proliferation and synthesis of extracellular matrix (ECM). In this study, we designed a novel GAM with embedded chitosan/plasmid nanoparticles encoding platelet derived growth factor (PDGF) based on porous chitosan/collagen composite scaffold. The chitosan/collagen scaffold acted as three‐dimensional carrier and chitosan nanoparticles condensed plasmid DNA. The plasmid DNA entrapped in the scaffolds showed a sustained and steady release over 6 weeks and could be effectively protected by chitosan nanoparticles. MTT assay demonstrated that periodontal ligament cells (PDLCs) cultured into the novel GAM achieved high proliferation. Luciferase reporter gene assay displayed that the novel GAM could express 1.07×104 LU/mg protein after 1 week and 8.97×103 LU/mg protein after 2 weeks. The histological results confirmed that PDLCs maintained a fibroblast figure and the periodontal connective tissue‐like structure formed in the scaffolds after 2 weeks. Semi‐quantitative immunohistochemical results suggested that PDGF protein expressed at a relatively high level after 2 weeks. From this study, it can be concluded that the novel GAM had potential in the application of periodontal tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
UHMWPE carrying estradiol to treat the particle‐induced osteolysis—Processing and characterizing
Authors: Liu Aiqin , Qu Shuxin , Chao Mengmeng , Zhu Minhao , Weng Jie , Zhou Zhongrong
Published: June 2008

The objective of this study was to explore the possibility of UHMWPE implant used as the drug carrier to treat particle‐induced osteolysis. 17β‐estradiol (E2), which had the potential application on osteolysis treatment and the high melting point, was added into UHMWPE powder to produce UHMWPE‐E2 composites through hot press processing. The hydrophobicity, crystallinity, mechanical properties, and wear performance of the UHMWPE‐E2 were characterized compared with the control UHMWPE. The thermal analysis and Fourier Transform Infrared Spectroscopy results demonstrated that the hot press processing would not alter the functional groups of E2 in this study. There were no significant differences in the hydrophobicity and crystallinity between the UHMWPE‐E2 and UHMWPE. The UHMWPE‐E2 showed satisfying mechanical properties, including ultimate tensile strength (47.2 ± 3.6 MPa), yield strength (25.0 ± 0.6 MPa) and elongation at break (320 ± 25.5 %), which were similar with the control UHMWPE. The friction coefficients and worn scars were similar between the UHMWPE‐E2 and the control UHMWPE. The wear mechanism of the UHMWPE‐E2 and UHMWPE both were abrasive wear under dry friction. The UHMWPE‐E2 possesses the approving mechanical properties and wear performance compared with the control UHMWPE, which might be used as the potential implanted drug carrier to prevent the particle‐induced osteolysis in joint replacements. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Trace concentrations of vitamin E protect radiation crosslinked UHMWPE from oxidative degradation
Authors: Kurtz S. M. , Dumbleton J. , Siskey R. S. , Wang A. , Manley M.
Published: June 2008

The effect of very low concentrations of Vitamin E on the stability and mechanical behavior of UHMWPE remains unknown. We tested the hypothesis that the oxidation resistance of Vitamin E‐blended UHMWPE would be influenced by trace doses of antioxidant, resin, and radiation treatment. Trace concentrations (≤500 ppm w/w%) of α‐tocopherol (Vitamin E) were blended separately with GUR 1020 and 1050 resins and molded into disks. From each disk, three groups of 10 mm thick blocks were machined: (1) no irradiation (control); (2) 30 kGy of gamma irradiation in nitrogen; and (3) 75 kGy of gamma irradiation in air. Specimens were subjected to three aging protocols: (a) no aging (control); (b) two weeks and (c) four weeks of accelerated aging in accordance with ASTM F 2003 (i.e., 70°C and 5 atm oxygen). The minimum concentration of Vitamin E needed to stabilize UHMWPE during our accelerated tests depended upon the method of radiation processing. For the 30 and 75 kGy irradiated materials, the addition of 125 ppm or more Vitamin E was sufficient to maintain baseline mechanical and chemical properties through two weeks of accelerated aging. For these groups, the addition of 375 ppm or 500 ppm, respectively, was necessary to maintain baseline mechanical and chemical properties throughout the four‐week accelerated aging period. UHMWPE resin molecular weight did not have an effect on oxidation behavior. The results of this experiment therefore supported our hypotheses that trace concentrations of Vitamin E, coupled with radiation treatment—but not resin grade—influence the mechanical and oxidative degradation behavior of UHMWPE. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res 90A: 549–563, 2008
Repair of long intercalated rib defects in dogs using recombinant human bone morphogenetic protein‐2 delivered by a synthetic polymer and beta‐tricalcium phosphate
Authors: Hoshino Masatoshi , Egi Takeshi , Terai Hidetomi , Namikawa Takashi , Kato Minori , Hashimoto Yusuke , Takaoka Kunio
Published: June 2008

Long intercalated defects in canine ribs can be repaired successfully using porous beta‐tricalcium phosphate (β‐TCP) cylinders, infused with a biodegradable polymer (poly D,L‐lactic acid‐polyethylene block copolymer) containing recombinant human bone morphogenetic protein‐2 (rhBMP‐2). We previously reported the successful regeneration of bony rib and periosteum defects using β‐TCP cylinders containing 400 μg of rhBMP‐2. To reduce the amount of rhBMP‐2 and decrease the time required for defect repair, we utilized a biodegradable polymer carrier, in combination with rhBMP‐2 and the porous β‐TCP cylinders. An 8 cm long section of rib bone was removed and replaced with an implant comprised of the porous β‐TCP cylinders and the polymer containing 80 μg of rhBMP‐2. Six weeks after surgical placement of the β‐TCP cylinder/polymer/BMP‐2 implants, new rib bone with an anatomical configuration and mechanical strength similar to the original bone was regenerated at the defect site. The stiffness of the regenerated ribs at 3, 6, and 12 weeks after implantation of the composite implant was significantly higher than that of ribs regenerated by implantation of rhBMP‐2/β‐TCP implants. Thus, addition of the synthetic polymer to the drug delivery system for BMP potentiated the bone‐regenerating ability of the implant and enabled the formation of mechanically competent rib bone. This new method appears to be applicable to the repair of intercalated long bone defects often encountered in clinical practice. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Matrix therapy in regenerative medicine, a new approach to chronic wound healing
Authors: Barbier‐Chassefière V. , Garcia‐Filipe S. , Yue X. L. , Kerros M. E. , Petit E. , Kern P. , Saffar J. L. , Papy‐Garcia D. , Caruelle J. P. , Barritault D.
Published: June 2008

Nonhealing wounds remain a major health problem whose treatment is challenging and costly. Treatments based on cells or growth factors are still not very effective. We developed an entirely novel strategy consisting in treatment of the wound‐tissue matrix with biopolymers engineered to mimic heparan sulfates called OTR4120. This compound was dextran polymer with sulfated and carboxymethyl groupments. After binding to matrix proteins, the heparan‐sulfate‐mimicking polymer protects the microenvironment, maintaining the normal production of signals and growth factors needed for healing to occur. Here, we show that a specific biopolymer accelerates ulcer closure and improves re‐epithelialization and dermal‐matrix‐component remodeling. OTR4120 treatment was associated with faster maturation of epidermal structures, most notably regarding the number of epithelial‐cell layers, and with an appearance that more closely resembled normal skin. Treatment had also a main effect on collagen I and III expression. Necrotic skin ulcers induced in mice with doxorubicin recovered normal collagen levels and organization, with no evidence of fibrosis. Thus, appropriate polymer‐based matrix therapy is a valid and simple alternative to regenerative medicine. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Assessment of the biocompatibility of photosensitive polyimide for implantable medical device use
Authors: Sun Y. , Lacour S. P. , Brooks R. A. , Rushton N. , Fawcett J. , Cameron R. E.
Published: June 2008

Polyimides have been widely used for biosensor encapsulation and more recently as substrates for neural implants. They have excellent thermal stability, high chemical resistance, and can be prepared as thin, flexible films. Photosensitive polyimides present similar physical properties to polyimides, and have the advantage that they can be photo‐lithographically patterned. However, to date little data on their biocompatibility has been reported. Two commercially available polyimides (PI) and one photo‐sensitive polyimide (PSPI) were evaluated in vitro using the ISO 10993 standard on biocompatibility. The materials were Dupont Kapton foil HN, HD Microsystem PI2611, and Fujifilm Durimide 7020 (PSPI). PI2611 and Durimide 7020 were spin‐coated on silicon wafers, cured at temperatures ranging from 150 to 450°C, and sterilized by autoclave. All materials were evaluated using a scanning electron microscope pre‐ and postcell culture. Cell viability was determined by an MTS assay. Their mechanical properties and stability during cell culture as a function of time and environment were investigated by nanoindentation. The MTS results show that PSPI is noncytotoxic compared with the negative control of polyethylene and the conventional PIs tested. Fibroblast adhesion, morphology, and spreading were good and better on the PSPI substrate than on the PI2611. Schwann cell appearance was similar on each of the PIs and the PSPI tested. The results suggest that PSPIs may have potential use for biological microsystem and neuroprosthetic applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Elastic and macroporous agarose–gelatin cryogels with isotropic and anisotropic porosity for tissue engineering
Authors: Tripathi Anuj , Kathuria Neeraj , Kumar Ashok
Published: June 2008

The focus of this work was to design a macroporous scaffold with controlled porosity in isotropic and anisotropic manner for tissue‐engineering applications. Agarose–gelatin scaffolds were synthesized by cryogelation method, in which agarose was used to improve the mechanical characteristics and gelatin‐provided amiable property of elasticity, cell adhesion, and cell proliferation in the scaffold. Agarose–gelatin (8%) cryogels synthesized in two different solvent systems (i.e., water and 0.1% acetic acid) at subzero temperature (−12°C) showed well‐interconnected porous structure. The agarose–gelatin cryogel synthesized in water solvent system (WSS) showed gradient porosity with an average pore diameter of a monolith (four sections from bottom to top; height 5 mm and diameter 13 mm each) ranging from 76 to 187 μm. The monolith of agarose–gelatin synthesized in 0.1% acetic acid solvent system (0.1% ASS) did not show any remarkable difference in average pore diameter of a monolith to their whole column length as revealed by scanning electron microscopy (SEM). These cryogels swelled up to ∼90% of their capacity within 1 min. The aggregate tensile modulus showed good elasticity of the cryogels, in which agarose–gelatin synthesized in WSS showed higher tensile modulus, that is, 380.23 ± 63.97 kPa in comparison with agarose–gelatin synthesized in 0.1% ASS, i.e., 278.08 ± 94.08 kPa. The unconfined fatigue observation with varying strain (10–40%) and varying frequencies (2 and 5 Hz) showed no deformation of cryogels. The fibroblast (Cos‐7) cell line seeded on the scaffold displayed good cell attachment in both types of cryogels and MTT assay showed good cell compatibility and favorable conditions for cell proliferation. These results indicate that agarose–gelatin cryogels can be a promising material of choice for tissue‐engineering applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Proliferation and differentiation of osteoblast‐like MC3T3‐E1 cells on biomimetically and electrolytically deposited calcium phosphate coatings
Authors: Wang Jiawei , de Boer Jan , de Groot Klaas
Published: June 2008

Biomimetic and electrolytic deposition are versatile methods to prepare calcium phosphate coatings. In this article, we compared the effects of biomimetically deposited octacalcium phosphate and carbonate apatite coatings as well as electrolytically deposited carbonate apatite coating on the proliferation and differentiation of mouse osteoblast‐like MC3T3‐E1 cells. It was found that MC3T3‐E1 cells cultured on the biomimetically deposited carbonate apatite coating demonstrated the greatest proliferation rate and the highest differentiation potential. Cells on the biomimetically deposited octacalcium phosphate coating had lower proliferation rate before day 7, but higher after that, than those on the electrolytically deposited carbonate apatite coating. There was no difference on the expression of early differentiation markers, that is, alkaline phosphatase activity and collagen content, between biomimetically deposited octacalcium phosphate and electrolytically deposited carbonate apatite coatings. However, higher expression of late differentiation markers, that is, osteocalcin and bone sialoprotein mRNA, was found on the biomimetically deposited octacalcium phosphate coating on day 14. These results suggest that the difference in in vitro osteoblast cell performance of calcium phosphate coatings might relate to their physicochemical properties. Biomimetic carbonate apatite coating is the most favorable surface for the proliferation and differentiation of MC3T3‐E1 cells. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Electrochemical processes of nucleation and growth of calcium phosphate on titanium supported by real‐time quartz crystal microbalance measurements and X‐ray photoelectron spectroscopy analysis
Authors: Eliaz Noam , Kopelovitch William , Burstein Larisa , Kobayashi Equo , Hanawa Takao
Published: June 2008

Real‐time, in situ electrochemical quartz crystal microbalance (EQCM) measurements are conducted to better understand the electrocrystallization of calcium phosphates (CaP) on CP‐Ti. X‐ray photoelectron spectroscopy is used to identify the exact phase deposited, so that reliable estimation of the electrochemical processes involved is made. Analysis of the integrated intensity of the oxygen shake‐up peaks, in combination with the determination of Ca/P and O/Ca atomic ratios, enables to determine unambiguously that the octacalcium phosphate (OCP) is formed. Its role as a precursor to hydroxyapatite (HAp) is discussed. After an incubation period, the process by which OCP is formed follows a Faradaic behavior. The incubation time may be related to the need for local increase of pH before precipitation from solution can occur. The standard enthalpy of activation is ∼40 kJ/mol, which excludes diffusion‐controlled processes from being rate determining. The OCP deposit has thickness ≈0.61 μm, apparent density ≈ 0.95 g/cm3, 63.6% porosity, and deposition rate of 23.5 ng/(cm2 s) or 15 nm/min. The low‐equivalent weight value of 20.5 g/equiv, and the associated remarkably high number of electrons transferred in the reaction n ≈ 24, indicates that most of the current is consumed either by electrolysis of water or by a complex set of parasitic reactions. The low‐solubility product allows precipitation of CaP even at relatively low concentrations of calcium and phosphate/hydrogen phosphate ions. It is shown that HAp most likely forms via transformation of precursor phases, such as OCP, rather than directly. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Quantitative analysis of osteoblast‐like cells (MG63) morphology on nanogrooved substrata with various groove and ridge dimensions
Authors: Yang Jung‐Yen , Ting Yen‐Chung , Lai Juin‐Yih , Liu Hsuan‐Liang , Fang Hsu‐Wei , Tsai Wei‐Bor
Published: June 2008

Nanotextured silicon substrata with parallel ridges separated by grooves with equal width from 90 to 500 nm, were fabricated by electron beam lithography and dry etching techniques. Osteoblast‐like cells, MG‐63, were cultured on the sterilized nanopatterned substrata for 4 or 24 h, and then imaged by scanning electron microscopy. The influence of substrate topography on cell morphology was analyzed by image software. We found the initially cells spread faster on the nanopatterned surfaces than on the flat surface, suggesting that surface anisotropic feature facilitates initial cell extension along its direction. However, because of inhibition of cell lateral expansion across nanogrooved surfaces, the cells on the nanogrooved surface did not further expand laterally, and cell spreading area was less than that on the flat surface after 24 h of incubation. Cells elongated and aligned along the direction of grooves on all the nanopatterned substrata. Furthermore, fluorescence staining of cell nuclei indicated that the nuclei of the cells cultured on the nanopatterned surfaces also displayed a more elongated and aligned morphology along the direction of the grooves. Since cell shape and orientation influence cell functions and alignment of extracellular matrix secreted by cells, our results may provide the information regarding responses of osteoblasts to the nanostructure of collagen fibrils, and benefit bone tissue engineering and surface design of orthopedic implants. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Effect of ring‐opening polymerization condition on the characteristic and mechanical properties of hydroxyapatite/poly(ethylene glutarate) biomaterials
Authors: Monvisade Pathavuth , Siriphannon Punnama , Tapcharoen Walailak
Published: June 2008

Preparation of hydroxyapatite/poly(ethylene glutarate) (HAp/PEG) composites was carried out by ring‐opening polymerization (ROP) of cyclic oligo(ethylene glutarate) in porous HAp scaffolds using various reaction temperatures and times. The content of ROP‐PEG interpenetrated into the porous HAp scaffold was about 13–18 wt % with the values of number average molecular weight ($ \overline {M_{\rm n} } $) and weight average molecular weight ($ \overline {M_{\rm W} } $) of 2120–3630 and 2760–5250 g/mol, respectively. The increase in polymerization time and temperature brought about increase in molecular weight of ROP‐PEG, but decrease in its content. Compressive strength and compressive modulus of the HAp/PEG composites were about 5.8–20.1 and 105–208 MPa, respectively. These mechanical properties depend upon the effects of distribution, content, and molecular weight of ROP‐PEG in the composites. In vitro bioactivity of the HAp/PEG composites was studied by soaking them in simulated body fluid (SBF) for 28 days. The formation of HAp nanocrystal on the composite surfaces through the consumption of calcium and phosphorus from the SBF solution was observed after soaking, indicating the bioactivity of these HAp/PEG composites. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Development of a self‐cleaning sensor membrane for implantable biosensors
Authors: Gant Rebecca M. , Hou Yaping , Grunlan Melissa A. , Coté Gerard L.
Published: June 2008

Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature‐modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self‐cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles (∼219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33–34°C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature‐modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP‐H2B 3T3 fibroblast cells. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Preparation and characterization of bioactive calcium silicate and poly(ϵ‐caprolactone) nanocomposite for bone tissue regeneration
Authors: Wei Jie , Heo S. J. , Liu Changsheng , Kim D. H. , Kim S. E. , Hyun Y. T. , Shin Ji‐Wang , Shin Jung‐Woog
Published: June 2008

A novel biocomposite of nanosized calcium silicate (n‐CS) and poly(ϵ‐caprolactone) (PCL) was successfully fabricated directly using n‐CS slurry, not dried n‐CS powder, in a solvent‐casting method. The in vitro bioactivity of the composite was evaluated by investigating the apatite‐forming ability in simulated body fluid. A proliferation assay with mouse L929 fibroblasts was used to test the in vitro biocompatibility. The composition, hydrophilicity, and mechanical properties were also evaluated. Results suggest that the incorporation of n‐CS could significantly improve the hydrophilicity, compressive strength, and elastic modulus of n‐CS/PCL composites, with the enhancements mainly dependent on n‐CS content. The n‐CS/PCL composites exhibit excellent in vitro bioactivity, with surface apatite formation for 40% (w/w) n‐CS (C40) exceeding that of 20% (w/w) n‐CS (C20) at 7 and 14 days. The Ca/P ratios of apatite formed on C20 and C40 surfaces were 1.58 and 1.61, respectively, indicating nonstoichiometric apatite with defective structure. Composites demonstrated significantly better cell attachment and proliferation than that of PCL alone, with C40 demonstrating the best bioactivity. The apatite layers that formed on the composite surfaces facilitated cell attachment (4 h) and proliferation during the early stages (1 and 4 days). Collectively, these results suggest that the incorporation of n‐CS produces biocomposites with enhanced bioactivity and biocompatibility. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria
Authors: Korotkov Sergey M. , Emel'yanova Larisa V. , Yagodina Olga V.
Published: June 2008

We studied action of inorganic phosphate (Pi) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. Pi markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of succinate‐energized mitochondria in the TlNO3 medium. A valinomycin‐induced decrease of K+‐diffusion potential was also accelerated by Tl+ in the presence of Pi. The mitochondrial permeability transition pore in the medium containing Ca2+, TlNO3, and nitrates of univalent cations was distinctly stimulated by Pi. However, Pi did not affect both the Tl+‐stimulated swelling of nonenergized mitochondria in the TlNO3 medium and swelling of energized mitochondria in the Tl acetate medium. Respiration stimulated by 2,4‐dinitrophenol and monoamine oxidase activity of energized mitochondria were not affected by Tl+ regardless of the presence of Pi. We suggested that stimulation by Pi of toxic action of Tl+ in mitochondria and cells could be due to even greater enhancement of uncoupling of mitochondria as shown by an additional increase of swelling and state 4, and in the greater probability of opening of MPTP in the presence of Pi and Ca2+. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:148–157, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20215
Preparation and adsorption characteristic of polymeric microsphere with strong adsorbability for creatinine
Authors: Gao Baojiao , Yang Ying , Wang Jian , Zhang Yan
Published: June 2008

Cross‐linking terpolymer microspheres (HEMA/NVP/MBA; it can also be designated as HEMA/NVP because HEMA and NVP are main components) with an average diameter of 180 µm, were prepared via inverse suspension copolymerization by using 2‐hydroxyethyl methacrylate (HEMA) and N‐vinylpyrrolidone (NVP) as monomers and N,N′‐methylene bisacrylamide (MBA) as cross‐linked agent. The microsphere HEMA/NVP was chemically modified with 3,5‐dinitrobenzoyl chloride (DNBC), and the functional microsphere DNBZ‐HEMA/NVP, on which a great number of 3,5‐dinitrobenzoate group (DNBZ) were bound, was obtained. The functional microsphere DNBZ‐HEMA/NVP were characterized with FTIR and the chemical analysis method. The adsorption characteristics and mechanism of the absorption of DNBZ‐HEMA/NVP for creatine was mainly studied. The results of static adsorption experiments show that the functional microsphere DNBZ‐HEMA/NVP has very strong adsorption ability for creatinine, and the saturated adsorption amount is 25 mg/g. The adsorption capacity of the functional microsphere DNBZ‐HEMA/NVP for creatinine is enhanced 20 times as against unmodified microsphere HEMA/NVP. The adsorption capacity is smaller, at lower and higher pH, and has a maximum as pH 8.5. The higher the salinity of the medium, the smaller the adsorption capacity. The adsorption capacity decreases with increasing temperature. The study results show that the adsorption of the microsphere DNBZ‐HEMA/NVP for creatinine is ascribed to a chemical adsorption by driving of electrostatic interaction. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:166–174, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20221
Caffeic acid protects human peripheral blood lymphocytes against gamma radiation‐induced cellular damage
Authors: Devipriya Nagarajan , Sudheer Adluri Ram , Menon Venugopal P.
Published: June 2008

In the present study, we investigated in vitro radioprotective potential of caffeic acid (CA), a naturally occurring catecholic acid against gamma radiation‐induced cellular changes. Different concentrations of CA (5.5, 11, 22, 44, 66, and 88 µM) were incubated with lymphocytes for 30 min prior to γ‐irradiation, and micronuclei (MN) scoring and comet assay were performed to fix the effective concentration of CA against γ‐irradiation. Among all concentrations, 66 µM of CA showed the optimum protection by effectively decreasing the MN frequencies and comet attributes. From the above‐mentioned results, 66 µM of CA was selected as the effective concentration and was further used to investigate its radioprotective efficacy. For that purpose, a separate experiment was carried out on the lymphocytes in which lymphocytes were preincubated with CA (66 µM) and were exposed to different doses of radiation (1, 2, 3, and 4 Gy). Genetic damage (MN, dicentric aberration, and comet attributes) and biochemical changes were measured. Gamma‐irradiated lymphocytes showed a dose‐dependent increase in the genetic damage and thiobarbituric acid reactive substances, accompanied by the significant decrease in the antioxidant status, whereas CA pretreatment positively modulated all the radiation‐induced changes through its antioxidant potential. The current study demonstrates that CA is effective in protecting lymphocytes against radiation‐induced toxicity and encourages further in vivo study to evaluate radioprotective efficacy of CA. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:175–186, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20228