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Study of aging of silicone rubber biomaterials with NMR
Pfleiderer, B., P. Xu, et al. (1995), J Biomed Mater Res 29(9): 1129-40.
Abstract: Multinuclear nuclear magnetic resonance (NMR) spectroscopy (29Si, 13C, 1H) is used to characterize the aging process of silicone rubber-based biomaterials in a rat model. 1H NMR relaxation measurements (spin-lattice, T1, and spin-spin, T2, relaxation times) were performed to better understand the molecular dynamics of polysiloxane chains in implants. After 1 year of implantation in animals, changes in the 1H T2 relaxation times and the NMR spectra were observed in polydimethylsiloxane, Silastic sheets and chin implants, while these measurements remain unchanged in finger joints. Very small amounts of fat were detected in all types of silicone rubber implants at the end of the implantation period. This work shows that free silicone migrates from the implants to adjacent tissues and distant sites, such as spleen or liver, and is chemically modified.

Study of cellular responses to polymeric biomaterials using the differential display method
Kato, S., A. Kishida, et al. (2000), J Biomater Sci Polym Ed 11(4): 333-40.
Abstract: In this study, we attempted to detect altered gene expressions in the cells that had adhered to various surfaces using the differential display method. Thioglycollate-elicited peritoneal exudate cells (PEC) and mouse fibroblast (L929) cells were cultured on the polymer films. After a predetermined time, the total RNA was isolated from cells and the differential mRNA expressions were evaluated by RT-PCR method. As a result, in the differential display of amplified cDNA from PEC, the different patterns of cDNA fragments among the samples were obtained. This indicates that there were many different mRNA expressions depending on the polymer surfaces. The use of differential method was proven to be useful for studying cell-polymer interaction.

Study of diopside ceramics for biomaterials
Nonami, T. and S. Tsutsumi (1999), J Mater Sci Mater Med 10(8): 475-9.
Abstract: Diopside was prepared by sintering a powder compact of composition CaO-MgO-2SiO2 at 1300 degreesC for 2 h. The bending strength of diopside was 300 MPa and the fracture toughness was 3.5 MPa m1/2. It was proved that diopside has no general toxicity in cell culture. Diopside implanted in rabbits came in close contact with the newly grown bone. X-ray microanalysis spectral diagrams show a change of composition across the junction from the diopside to the newly grown bone. High-resolution transmission electron microscopy revealed crystal growth at the interface between diopside and the newly grown bone, and continuity between diopside lattices and those of the new crystals.

Study of gelatinized marrow stroma osteoblasts and true bone ceramic active bone
Gong, T. F., R. Y. Xia, et al. (2005), Chin J Traumatol 8(2): 91-5.
Abstract: OBJECTIVE: To investigate a new method to construct tissue-engineering bone that will be applicable clinically. METHODS: The cultured 5th generation rabbit bone marrow stroma osteoblasts (MSO) was dissolved in 3% sodium alginate solution (the final concentration of sodium alginate in the solution being 1%, and MSO, 5x10(6)/L), and then inoculated into prepared true bone ceramic (TBC) and gelatinized the bone by dribbling with calcium gluconate. The standard bone defect models were made in 48 adult New Zealand rabbit's both radius. Among the 48 rabbits, 24 were in Groups A and B, in which the left radius was implanted with gelatinized MSO-TBC (Group A) and right radius implanted with autograft-bone (Group B); and the other 24 were in control group whose left radius was implanted with non-gelatinized MSO-TBC (Group C) and right radius implanted with gelatinized TBC (Group D). Outcomes of the implanted bones were assessed by radiology, pathological histology, osteogenetic quantitative analysis, and biomechanics at 2, 4, 8, 12 weeks postoperatively. RESULTS: In Groups A and B, a satisfactory bone reparation and bony union was noted within 12 weeks. In Groups C and D, bone reparation was not satisfied compared with Group A in terms of ostogenetic quantity and biomechanics. CONCLUSIONS: Gelatinized MSO-TBC is an ideal artificial active bone that overcomes TBC shortcomings of fragileness and smooth surface that is not eligible for seed cell's adhesion. It is promising to put into clinical use extensively.

Study of graft copolymerization of N-maleamic acid-chitosan and butyl acrylate by gamma-ray irradiation
Huang, M., X. Shen, et al. (2005), Int J Biol Macromol 36(1-2): 98-102.
Abstract: N-maleamic acid-chitosan was synthesized and characterized by Fourier transform infrared spectra analysis (FT-IR) and 1H NMR. The graft copolymerization of N-maleamic acid-chitosan and butyl acrylate (BA) in acetic acid aqueous solution was investigated, using the gamma-ray of 60Co gamma-irradiation method. DSC (differential scanning calorimetry) trace of N-maleamic acid-chitosan-g-PBA has a glass-transition temperature (Tg) at -42 degrees C. The thermal stabilities of the graft copolymer were studied by the thermal gravimetric analysis (TGA). The effect of synthesis variables in the graft copolymerization have been discussed in the light of grafting efficiency, grafting percentage, and homopolymer percentage. Increasing grafting percentage was observed when the monomer concentration and total dose were increased or when the reaction temperature was decreased.

Study of implanted biomaterial functionality by diphosphonate molecules labeled with radioactive 99mTc
Irigaray, J. L., H. Oudadesse, et al. (1999), Biol Trace Elem Res 71-72: 629-33.
Abstract: An implanted biomaterial can be transformed into young bone after some months, but it has not necessary reached full biofunctionality. Mineral concentration kinetics and crystal-structure studies, still being carried out in our group, are completed here by biofunctionality determinations. A natural coral is implanted in vivo at the cortical level of the femoral diaphyoff++ in rabbits. Diphosphonates molecules labeled with radioactive 99mTc are then injected in rabbits and the fixation of the radioactivity is analyzed in several sites for 8 mo after the implantation. Nuclear instruments and methods are used for the measurements. Four successive cycles of osseous remodeling are determined before reaching a biofunctional phase.

Study of novel rosin-based biomaterials for pharmaceutical coating
Fulzele, S. V., P. M. Satturwar, et al. (2002), AAPS PharmSciTech 3(4): E31.
Abstract: The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.

Study of the biodegradation and in vivo biocompatibility of novel biomaterials
Fulzele, S. V., P. M. Satturwar, et al. (2003), Eur J Pharm Sci 20(1): 53-61.
Abstract: The degradation of two rosin-based biomaterials, the glycerol ester of maleic rosin (GMR) and the pentaerythritol ester of maleic rosin (PMR), was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. Free films of the two biomaterials with mean thickness 0.4+/-0.02 mm were used for the study. The initial biocompatibility was followed by microscopic examination of the inflammatory tissue response to the implanted films. Sample weight loss and molecular weight decline of the free films was used to monitor the degradation quantitatively, while surface morphological changes were analysed for qualitative estimation. Biocompatibility response was followed on post-operative days 7, 14, 21 and 28 and compared with those of poly(DL-lactic-co-glycolic acid) (PLGA) (50:50) films. Both biomaterials showed slow in vitro degradation when compared with the in vivo rate. The mechanism followed was, however, bulk degradation of the films. The penta-esterified form of maleic rosin was observed to degrade more rapidly than glycerol esterified maleic rosin. The acute and subacute inflammatory reactions were characterized by fibrosis at the end of 28 days. The biomaterials showed reasonable tissue tolerance to the extent evaluated. There was a total absence of tissue necrosis or abscess formation for all implanted films. The response, although not identical to that of PLGA, is reasonable, promising new drug delivery applications for rosin biomaterials.

Study of the influence of beta-radiation on the properties and mineralization of different starch-based biomaterials
Oliveira, A. L., J. F. Mano, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 560-9.
Abstract: In this work, the effects of beta-radiation are assessed, for the first time, on starch-based biodegradable polymers, with the aim of using it as an alternative sterilization process to the previously studied sterilization methods. Different doses of radiation were used in order to investigate the possibility of using this sterilization technique as a treatment to tailor the surface and bulk properties (namely mechanical) of these polymers. The as-treated substrates were characterized by water-uptake measurements and contact angle (theta) measurements. The mechanical properties of the materials were characterized by tensile tests by means of ultimate tensile strength (UTS) and strain at break (epsilon). The fracture of the surfaces was observed by scanning electron microscopy (SEM). Dynamic mechanical analysis (DMA) was also used to characterize the viscolelastic behavior of the irradiated materials. The main effect of sterilization with beta-radiation over the starch-based polymers seems to be a surface modification by an increase of the hydrophilicity. Nevertheless, because beta-radiation did not significantly affect the mechanical properties, it can be regarded as an effective way of modifying the surface for applications were more hydrophilic surfaces are desirable.

Study of the release mechanism of diltiazem hydrochloride from matrices based on chitosan-alginate and chitosan-carrageenan mixtures
Tapia, C., V. Corbalan, et al. (2005), Biomacromolecules 6(5): 2389-95.
Abstract: The aim of this work was to establish the diltiazem hydrochloride release mechanism from the chitosan-alginate matrix tablet (MCB/AS) and chitosan-carrageenan matrix tablet (MCS/CSI). The weight loss for MCS/CSI is mainly due to the weight loss of the matrix while for MCB/AS it is mainly due to the diltiazem hydrochloride released from the tablet. Using the Peppa's model the release order for MCS/CSI was n = 1.07 +/- 0.13 and for MCB/AS was n = 0.76 +/- 0.02. Thus, MCS/CSI has a transport mechanism, and for MCB/AS the drug release mechanism is a combined process of diffusion and relaxation. MCB/AS has an elastic modulus (G' = 10(5) Pa) one order of magnitude higher than MCS/CSI (G' = 10(4) Pa). MCB/AS is able to uptake solvent without disrupting the microstructure due to its high elastic modulus. Instead MCS/CSI showed a quick erosion process, which conducted to the tablet disintegration due to a fast solvent uptake process.

Study of the surface morphology of a cholesteryl tethering system for lipidic bilayers
Blasi, L., D. Pisignano, et al. (2005), Biochim Biophys Acta 1714(2): 93-102.
Abstract: The immobilization of functional molecules embedded in lipidic membranes onto inorganic substrates is of great interest for numerous applications in the fields of biosensors and biomaterials. We report on the preparation and the morphological characterization of a tethering system for lipidic bilayers, which is based on cholesteryl derivatives deposited on hydrophilic surfaces by self-assembling and microcontact printing techniques. The investigation of the structural properties of the realized films by atomic, lateral, and surface potential microscopy allowed us to assess the high quality of the realized cholesteryl layers.

Study on modification of collagen with chondroitin sulfate on the microcosmic level
Zhang, L., M. Hu, et al. (2005), Artif Cells Blood Substit Immobil Biotechnol 33(2): 215-26.
Abstract: To observe the changes during the process of modificating collagen with chondroitin sulfate (CS), a series of experiments was designed. Collagen scaffold was constructed by lyophilization. CS was attached into the scaffold through crosslinking. Solid-liquid phase separation method was used to shape 3D porous structure. Both kinds of scaffolds were investigated by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Electron Spectroscopy for Chemical Analysis (ESCA), Amino Acid Analyses (AAA), and so on for structures and characteristics. The results showed that CS could improve the properties of collagen both in biocompatibility and mechanical property. It increased the polar groups on the surface of scaffold and protected amino acid residues of collagen fiber. At the same time, the structure of scaffold became more regular because of the increase of polar groups. It was indicated that those were the real reasons for the improvement of modification.

Study on the photocatalytic reduction of dichromate and photocatalytic oxidation of dichlorvos
Chen, S. and G. Cao (2005), Chemosphere 60(9): 1308-15.
Abstract: In this paper, dichromate and dichlorvos are selected as the deputies of inorganic and organic pollutants, respectively, and TiO2/beads is used as a photocatalyst. The effects of various parameters, such as the amount of the photocatalyst, H2O2 concentration, metal ions, anions, pH value, and organic compounds on the photocatalytic reduction of dichromate and photocatalytic oxidation of dichlorvos are studied. From the studies, the differences of the parameters effect on the photocatalytic degradation of organic and inorganic pollutants are obtained. The results show that the optimum amount of the photocatalyst used is 6.0 g cm(-3) for the photocatalytic reactions. With the addition of a small amount of H2O2, the photocatalytic reduction of dichromate is inhibited while the photocatalytic oxidation of dichlorvos is accelerated. With the addition of trace amounts of Fe3+ or Cu2+, both the reactions are accelerated, and with the addition of Zn2+ and Na+, no obvious effects on the reactions are observed. Acidic solution is favorable for the photocatalytic reduction of dichromate; and acidic and alkaline solutions are favorable for the photocatalytic oxidation of dichlorvos. Adding SO4(2-), the photocatalytic oxidation is accelerated and adding Cl- the reaction is inhibited; and with the addition of trace amounts of SO4(2-), Cl- and NO3-, no obvious effects on the photocatalytic reduction of dichromate are observed. With the addition of methanol and toluene, the photocatalytic reduction of dichromate is accelerated, and the photocatalytic oxidation of dichlorvos is inhibited. The possible roles of the additives on the reactions are also discussed.

Study on the self-setting property and the in vitro bioactivity of beta-Ca2SiO4
Gou, Z., J. Chang, et al. (2005), J Biomed Mater Res B Appl Biomater 73(2): 244-51.
Abstract: This study sought to investigate the physical and chemical properties of beta-dicalcium silicate (beta-Ca(2)SiO(4)) in order to evaluate its use as an injectable bioactive cement filler. Workable beta-Ca(2)SiO(4) pastes with a liquid-to-powder (L/P) ratio of 1.0-1.2 could be injected for 10-30 min (nozzle diameter 2.0 mm) and enabled initial setting times of 60-180 min. The setting process yielded cellular structures with compressive strengths of 4.8-28.8 MPa after 2-28 days. The paste was soaked in simulated body fluid (SBF), and the results demonstrated that it exhibited a moderate degradation and could induce carbonated hydroxyapatite formation. The ionic products of the paste dissolution enhanced a proliferative response of fibroblasts compared with the cells cultured alone, and this cement could also support adhesion and spreading of the mesenchymal stem cells. Finally, with the use of gentamicin as a model drug, it was found that a high dose of drug release from the paste was maintained for 14 days, and there was a sustained release over 4 weeks. This combination of properties indicates that the novel beta-Ca(2)SiO(4) cement might be suitable for potential applications in the biomedical field, preferentially as materials for bone/dental repair and controlled drug-delivery systems.

Study on the synergetic degradation of chitosan with ultraviolet light and hydrogen peroxide
Wang, S. M., Q. Z. Huang, et al. (2005), Carbohydr Res 340(6): 1143-7.
Abstract: Chitosan was effectively degraded by hydrogen peroxide under irradiation with ultraviolet light. The existence of a synergetic effect on the degradation was demonstrated by means of viscometry. In addition, the optimal conditions of degradation were determined on the basis of orthogonal tests. The structure of the degraded product was characterized by Fourier-transform infrared spectra (FTIR) analysis and diffuse reflectance spectra (DRS) analysis. The mechanism of the degradation of chitosan was correlated with cleavage of the glycosidic bond.

Subacute toxicity testing of biomaterials using histopathologic evaluation of rabbit muscle tissue
Turner, J. E., W. H. Lawrence, et al. (1973), J Biomed Mater Res 7(1): 39-58.

Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model
Ayalasomayajula, S. P. and U. B. Kompella (2005), Eur J Pharmacol 511(2-3): 191-8.
Abstract: We have previously reported that repeated oral doses of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduced diabetes-induced retinal vascular endothelial growth factor (VEGF) expression [Ayalasomayajula, S.P., Kompella, U.B., 2003. Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 458, 283-289] and that retinal celecoxib delivery can be improved by several-fold following subconjunctival administration [Ayalasomayajula, S.P., Kompella, U.B., 2004. Retinal delivery of celecoxib is several-fold higher following subconjunctival administration compared to systemic administration. Pharm Res 21, 1797-1804]. The objective of the current study was to determine whether polymeric microparticles of celecoxib sustain retinal drug levels following subconjunctival administration and alleviate diabetes-induced oxidative stress in a streptozotocin-induced diabetic rat model. Biodegradable poly (lactide-co-glycolide) (PLGA; 85:15) microparticles of celecoxib were prepared using solvent evaporation method and characterized for their size, morphology, encapsulation efficiencies, and in vitro release. The celecoxib-PLGA microparticles or solution containing 75 microg of celecoxib was administered subconjunctivally to one eye (ipsilateral) of Sprague Dawley rats and drug levels in the retina, vitreous, lens, and cornea of ipsilateral and contralateral eyes were determined on 1, 7, and 14 days using high-performance liquid chromatography (HPLC). The effect of subconjunctivally administered celecoxib-PLGA microparticles on oxidative stress in day 14 diabetic rat retinas was determined by measuring the retinal glutathione (reduced (GSH) and oxidized (GSSG)), thiobarbituric acid reactive substances, and 4-hydroxynonenal levels using spectrofluorometric and colorimetric methods. Solvent evaporation method produced spherical celecoxib-PLGA microparticles with mean diameters of 3.9+/-0.6 microm and 68.5% loading efficiency. These microparticles sustained celecoxib release during the 49-day in vitro release study. Subconjunctivally administered celecoxib-PLGA microparticles sustained retinal and other ocular tissue drug levels during the 14-day study in rats. No detectable celecoxib levels were observed in the contralateral eye. The celecoxib-PLGA microparticles significantly inhibited the diabetes-induced increases in thiobarbituric acid reactive substance (P=0.012) and 4-hydroxynonenal levels (P=0.029). The particles also inhibited the GSH depletion and the increase in GSSH/GSH ratio associated with diabetes but the effects were not statistically significant (P=0.12). Thus, following subconjunctival administration, celecoxib-PLGA microparticles sustained retinal celecoxib delivery and inhibited diabetes-induced retinal oxidative damage, indicating their potential usefulness in treating diabetes-induced retinal abnormalities.

Subculture of chondrocytes on a collagen type I-coated substrate with suppressed cellular dedifferentiation
Kino-Oka, M., S. Yashiki, et al. (2005), Tissue Eng 11(3-4): 597-608.
Abstract: To evaluate the degree of cellular dedifferentiation, subculture of chondrocytes was conducted on a surface coated with collagen type I at a density of 1.05 mg/cm(2). In the primary culture, most of the cells were round in shape on the collagen (CL) substrate, whereas fibroblastic and partially extended cells were dominant on the polystyrene plastic (PS) substrate. Stereoscopic observation revealed that the round-shaped cells on the CL substrate were hemispherical with nebulous and punctuated F-actin filaments, whereas the fibroblastic cells on the PS substrate were flattened with fully developed stress fibers. This suggested that cell polarization was suppressed during culture on the former substrate. Although serial passages of chondrocytes through subcultures on the CL and PS substrates caused a decrease in the number of round-shaped cells, the morphological change was appreciably suppressed on the CL substrate, as compared with that on the PS substrate. It was found that only round-shaped cells formed collagen type II, which supports the view that cellular dedifferentiation can be suppressed to some extent on the CL substrate. Three-dimensional cultures in collagen gel were performed with cells isolated freshly and passaged on the CL or PS substrate. Cell density at 21 days in the culture of cells passaged on the CL substrate was comparable to that in the culture of freshly isolated cells, in spite of a significant reduction in cell density observed in the culture of cells passaged on the PS substrate. In addition, histological analysis revealed that the expression of glycosaminoglycans and collagen type II was of significance in the collagen gel with cells passaged on the CL substrate, and likewise in the gel with freshly isolated cells. This indicated that the CL substrate could offer a monolayer culture system for expanding chondrocyte cells.

Subcutaneous xenotransplantation of bovine pancreatic islets
Figliuzzi, M., R. Cornolti, et al. (2005), Biomaterials 26(28): 5640-7.
Abstract: Transplantation of pancreatic islets in diabetes is currently limited by the need of immunosuppressive therapy. The present study was designed to test an immunoprotection planar device for subcutaneous xenotransplantation of pancreatic islets in the diabetic rat. We tested three different devices made of polyethersulfone hollow fibers. In all diabetic rats, implantation of islet-containing devices promptly normalized hyperglycemia. In vitro membrane permeability to glucose was correlated with implant function duration. These data confirm that bovine islets contained within devices and implanted subcutaneously remain functional for several days. Strategies to prolong islet function may allow achieving successful long-term islet implantation in this attractive site.

Sublethal irradiation promotes invasiveness of neuroblastoma cells
Schweigerer, L., M. Rave-Frank, et al. (2005), Biochem Biophys Res Commun 330(3): 982-8.
Abstract: Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy. The mechanisms underlying this apparent discrepancy are still unclear. We have therefore investigated the effects of radiation on neuroblastoma cell behaviour in vitro. We show that sublethal doses of irradiation up-regulated the expression of the hepatocyte growth factor (HGF) and its receptor c-Met in some neuroblastoma cell lines. The increase in HGF/c-Met expression was correlated with enhanced invasiveness and activation of proteases degrading the extracellular matrix. Thus, irradiation at sublethal doses may promote the metastatic dissemination of neuroblastoma cells through activating the HGF/c-Met pathway and triggering matrix degradation.

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Last Modified: 8 February 2006