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The role of Galectin-1 in the interaction between chondrocytes and a lactose-modified chitosan
Marcon, P., E. Marsich, et al. (2005), Biomaterials 26(24): 4975-84.
Abstract: Evidences for the involvement of the Galectin-1 in the interaction of pig chondrocytes with a lactose-modified chitosan, namely Chitlac, are reported. The Chitlac glycopolymer has been shown to promote pig chondrocyte aggregation and to induce extracellular matrix production. Highly pure Galectin-1 was obtained from pig spleen by affinity chromatography and its identity was determined by ion spray mass spectrometry analysis of tryptic peptide fragments obtained after in-gel digestion. The complete sequence of pig Galectin-1 CDS was obtained by screening a pig EST database using human Galectin-1 sequence as template. The Galectin-1 cDNA was cloned into a pGEX-4T-1 expression vector and the recombinant protein was purified, characterized and used to produce a rabbit anti-serum. Recombinant Galectin-1 interacts in a dose-dependent manner with Chitlac as determined with ELISA assay. Expression level of galectin-1 gene, quantified by real-time PCR, was significantly higher in chondrocytes cultivated on Chitlac. In the same way, the presence of Chitlac stimulates secretion of Galectin-1 in culture medium that, by immunohistochemical analysis, revealed to be clustered on the surface of Chitlac-induced aggregates. These data indicate the role of Galectin-1 as a bridging agent between Chitlac and chondrocyte aggregates.

The role of graft materials in suture augmentation for tendon repairs and reattachment
Kummer, F. J. and K. Iesaka (2005), J Biomed Mater Res B Appl Biomater 74(2): 789-91.
Abstract: Various biomaterials have been used to augment sutures for the repair and reattachment of tendons. This study examined four different graft materials in a simple and reproducible model using chicken Achilles tendons to determine the strength and mechanism of suture reinforcement of tendon repairs. The graft materials tested were Gore-Tex(R) Soft Tissue Patch, Graftjacket, bovine pericardium, and an experimental graft material from Xylos Corporation. Testing was performed in shear to simulate forces on a torn tendon repair and pull-off to simulate those on a tendon reattachment to bone. Compared to unaugmented suture, grafts increased suture fixation strength from 10% to 60% in shear and from 0% to 36% in pull-off with the bovine pericardium graft, providing significant improvement in both tests. In no cases (even unaugmented) did the suture pull directly through the tendon, but instead sliced along it, demonstrating that the interface between the suture and the tendon determines fixation strength. Grafts function by increasing the area, friction, and nature of this interface, not by acting as a barrier for suture pull-through.

The role of macrophages in the tissues regeneration stimulated by the biomaterials
Muldashev, E. R., S. A. Muslimov, et al. (2005), Cell Tissue Bank 6(2): 99-107.
Abstract: Allogenic grafted tissues are subjected to biodegradation and replaced by the regenerate. To minimize the immune response and improve the rebuilding of tissues there was developed a technology to treat tissues with a cells elimination and dosed out extraction of proteoglycanes (Alloplant. With aim to clarify the role of macrophages in the tissues regeneration resulting implantation the biomaterials 112 rats were injected the allogenic and xenogenic (rabbit's) pulverized biomaterials in the form of suspension. Injections were performed subcutaneously into the animals' back by the base of the tail. The control group (14 rats) were injected a physiologic saline. Animals were killed by ether inhalation on day 2, 4, 7, 14, 30, 90 and 180 and tissue sections were studied by light and electron microscopy. The study showed the key role of the macrophages in resorption of the allogenic biomaterial and formation of the newly-formed tissue. Implantation of the biomaterial induced activity a great number of the mature macrophages, which completely lysed and resorbed the biomaterial particles. Expression TNFalpha was significantly higher whereas expression TGF-beta1 was significantly lower. With xenogenic biomaterial implantation there were less macrophages, their activity was restricted. Macrophages containing large vacuoles with an active endo- and exocytosis were revealed in the allogenic biomaterial implantation and were named 'matrix-forming macrophages'. We may suppose that these macrophages synthesize (or re-synthesize) proteoglycan component of the newly-formed collagen fibers. There was put forward a hypothesis about the two component mechanism of the collagen fibers formation.

The role of metal nanoparticles in remote release of encapsulated materials
Skirtach, A. G., C. Dejugnat, et al. (2005), Nano Lett 5(7): 1371-7.
Abstract: Laser mediated remote release of encapsulated fluorescently labeled polymers from nanoengineered polyelectrolyte multilayer capsules containing gold sulfide core/gold shell nanoparticles in their walls is observed in real time on a single capsule level. We have developed a method for measuring the temperature increase and have quantitatively investigated the influence of absorption, size, and surface density of metal nanoparticles using an analytical model. Experimental measurements and numerical simulations agree with the model. The treatment presented in this work is of general nature, and it is applicable to any system where nanoparticles are used as absorbing centers. Potential biomedical applications are highlighted.

The role of MMP-I up-regulation in the increased compliance in muscle-derived stem cell-seeded small intestinal submucosa
Long, R. A., J. Nagatomi, et al. (2006), Biomaterials 27(11): 2398-404.
Abstract: We have previously observed that muscle-derived stem cells (MDSC) seeded onto porcine small intestinal submucosa (SIS) increase the mechanical compliance of the engineered tissue construct [Lu SH, Sacks MS, Chung SY, Gloeckner DC, Pruchnic R, Huard J, et al. Biaxial mechanical properties of muscle-derived cell seeded small intestinal submucosa for bladder wall reconstitution. Biomaterials 2005;26(4):443-9]. To date, however, the initial remodeling events which occur when MDSC are seeded onto SIS have yet to be elucidated. One potential mechanism responsible for the observed increase in mechanical compliance is the release of matrix metalloproteinase-I (MMP-I). To investigate this finding, MDSC (approximately 1x10(6)) were cultured on single-layer SIS cell culture inserts (4.7cm(2)) for 1-10 days. MDSC MMP-I activity on SIS in the supernatant at 1, 3, 5, 7, and 10 days was determined using a collagenase assay kit. MMP-I activity of the MDSC/SIS was significantly higher (p<0.0025) after one day in culture compared to specimens collected from subsequent time points and the unseeded control. To further study the initial remodeling events, the impact of MMP-I on mechanical compliance was examined. SIS was incubated with 0.16U/mL collagenase-I for 3, 4.5, 5, and 24h, then biaxial mechanical testing was performed. After 5h of digestion with collagenase-I, mechanical compliance under 1MPa peak stress was increased by 7% in the circumferential direction, compared to control SIS. These findings suggest that the release of MMP-I in response to initial seeding on SIS and subsequent breakdown of collagen fibers is the mechanism responsible for an increase in mechanical compliance.

The role of osteopontin in foreign body giant cell formation
Tsai, A. T., J. Rice, et al. (2005), Biomaterials 26(29): 5835-43.
Abstract: Foreign body giant cells (FBGCs) are a hallmark of the foreign body reaction caused by biomaterial implantation and are thought to contribute to biomaterial degradation and the duration of the response. Osteopontin (OPN) is a secreted, acidic matricellular protein with multiple phosphorylation sites that is highly expressed at sites of inflammation. OPN wildtype and knockout mice were implanted with poly(vinyl alcohol) sponges and explanted at 14 days. OPN knockout mice had more foreign body giant cells but fewer macrophages surrounding the implants than their wildtype counterparts. In an in vitro human FBGC assay, addition of soluble OPN was found to reduce macrophage fusion to giant cells. These are the first studies to show a direct inhibitory role of OPN in FBGC formation in response to implantation.

The role of physicochemical properties of biomaterials and bacterial cell adhesion in vitro
Kitano, T., Y. Yutani, et al. (1996), Int J Artif Organs 19(6): 353-8.
Abstract: This study was undertaken to investigate the physicochemical aspects of the interaction between the surface of biomaterials and bacterial cell membranes in vitro, aimed at studying the mechanisms of bacterial adhesion to biomaterials. Correlations were made between the number of adherent bacterial cells (S. aureus) and each of the calculated components of surface free energy (i.e., dispersion, polarity and hydrogen bond) of biomaterials. The effect of antibodies to cell-adhesion molecules on bacterial adhesion was also studied using monoclonal antibodies to vitronectin receptor, fibronectin receptor and CD44. This study indicates the polarity component of surface free energy plays a dominant role in the process of bacterial adhesion at least in vitro. The number of cells adherent to materials decreased to 44-73% of the control value in the presence of antibodies tested, showing that cell adhesion molecules affect adherence to biomaterials. Moreover, the results suggested that bacterial adhesion was prevented by specific blockade of cell adhesion molecule receptors.

The role of proteins in the nucleation and formation of calcium-containing deposits on biomaterial surfaces
Vasin, S. L., I. B. Rosanova, et al. (1998), J Biomed Mater Res 39(3): 491-7.
Abstract: In experiments in vivo using diffusion chambers, the morphology and composition of calcium-containing deposits on natural and artificial biomaterials that had no direct contact with cells were studied using scanning electron microscopy with energy dispersion X-ray microanalysis. It was revealed that the formation of a protein layer containing protein-calcium complexes is the key event in biomaterial calcification. A mechanism of formation of a calcium-containing protein matrix that creates the conditions for supersaturation of the crystal-forming medium over critical value has been proposed. The formation of nuclei of insoluble calcium phosphate starts predominantly deep in an adsorbed protein layer enriched by calcium ions.

The role of regioselectively sulfated and acetylated polysaccharide coatings of biomaterials for reducing platelet and plasma protein adhesion
Baumann, H. (2001), Semin Thromb Hemost 27(5): 445-63.
Abstract: A brief survey is given about the role of natural polysaccharides such as heparin (HE), heparan sulfate (HS), chondroitin sulfate (CS), and dermatan sulfate (DS) in reducing blood coagulation and their potential use as athrombogenic coatings in the development of tailor-made athrombogenic biomaterials. Furthermore, known literature and new results about platelet adhesion on regioselectively modified polysaccharides such as HE, chitosan with HE-like functional groups, and sulfated cellulose are presented in two different perfusion systems at different shear rates. Regioselectively modified polysaccharides were tested as coatings of two polymers. The strongest influence on platelet adhesion was observed when the three regioselectively modified polysaccharides contained 6-O-sulfo- groups. No or little influence was seen with 3-O-sulfo- groups. A variable effect on platelet adhesion was found in position 2. N-sulfo- groups in HE induced a medium platelet adhesion, and O-sulfo- groups of iduronic acid moiety in HE induced none. Cellulose containing 2-O-sulfo- groups induced little platelet adhesion, and 2-N- sulfo- groups in chitosan induced a variable platelet adhesion response, depending on the N-SO(3)/NAc ratio. Preliminary plasma protein adhesion measurements on immobilized HE derivatives with four different fluorescence-labeled plasma proteins showed a regioselective influence with serum albumin and fibrinogen. 6-O-desulfated HE gave the strongest reduction in protein adsorption followed by N-desulfation and 2-O-desulfation; the lowest reduction was observed with 3-O-desulfation. Tailor-made athrombogenic coatings of HE should not carry high amounts of 6-O-sulfo- groups or of N-sulfo- groups. Regioselectively modified cellulose and chitosan may become suitable for tailor-made athrombogenic biomaterials when regioselective reactions are further optimized.

The role of surface thermodynamics in thromboresistance of biomaterials
Neumann, A. W., C. J. Hope, et al. (1975), J Biomed Mater Res 9(2): 127-42.
Abstract: A thermodynamic approach to the problem of platelet adsorption out of a suspension on to a smooth and homogeneous solid surface is developed. The interfacial tension values required may be estimated from contact angle data by means of an equation of state relation. According to the thermodynamic approach the functional dependence of platelet adsorption on surface tension of the solid differs according to whether the surface tension of the platelets is smaller or larger than the surface tension of the liquid in which they are suspended. The implications of this thermodynamic approach in situations where plasma proteins are present and the biomaterials surfaces may be heterogeneous and rough are discussed. Previous analyses using the critical surface tension of wetting and other surface-related parameters are compared with the thermodynamic analysis given here.

The safety of dental composite biomaterials
Salloum, T. (1999), J Can Dent Assoc 65(2): 79-80.

The scanning potential microscope: An instrument to image micro-corrosion processes on metallic biomaterials surfaces
Smith, S. M. and J. L. Gilbert (1991), Northwest Dent Res 2(2): 11-6.

The second annual symposium on nanomedicine and drug delivery: exploring recent developments and assessing major advances. 19-20 August 2004, Polytechnic University, Brooklyn, NY, USA
Vinogradov, S. (2004), Expert Opin Drug Deliv 1(1): 181-4.
Abstract: The meeting was dedicated to novel aspects of nanomedicine, including polymer drug delivery systems (DDS) and biomaterials. Self-assembled micellar DDS have been evaluated in terms of morphology, biological properties, and results of clinical trials. Important advances in the design of nanoparticles as DDS have been highlighted in various presentations. Unexpected issues of polymer-related biological effects, including gene expression, were stressed in relation to polymer DDS. Great potential of nanofabrication of biomaterials, and preliminary data on the design of polymer scaffolds were demonstrated in a number of reports. This symposium demonstrated how timely the development of nanosised DDS is, with advances in understanding the disease-related mechanisms, and outlined the major areas of application of nanomedicine technology.

The second decade of biomaterials development and evaluation: a time to apply the scientific method
Gott, V. L. (1972), Bull N Y Acad Med 48(2): 216-24.

The selection of a model microalgal species as biomaterial for a novel aquatic phytotoxicity assay
Bengtson Nash, S. M., P. A. Quayle, et al. (2005), Aquat Toxicol 72(4): 315-26.
Abstract: A phytotoxicity assay based on the ToxY-PAM dual-channel yield analyser has been developed and successfully incorporated into field assessments for the detection of phytotoxicants in water. As a means of further exploring the scope of the assay application and of selecting a model biomaterial to complement the instrument design, nine algal species were exposed to four chemical substances deemed of priority for water quality monitoring purposes (chlorpyrifos, copper, diuron and nonylphenol ethoxylate). Inter-species differences in sensitivity to the four toxicants varied by a factor of 1.9-100. Measurements of photosystem-II quantum yield using these nine single-celled microalgae as biomaterial corroborated previous studies which have shown that the ToxY-PAM dual-channel yield analyser is a highly sensitive method for the detection of PS-II impacting herbicides. Besides Phaeodactylum tricornutum, the previously applied biomaterial, three other species consistently performed well (Nitzschia closterium, Chlorella vulgaris and Dunaliella tertiolecta) and will be used in further test optimisation experiments. In addition to sensitivity, response time was evaluated and revealed a high degree of variation between species and toxicants. While most species displayed relatively weak and slow responses to copper, C. vulgaris demonstrated an IC10 of 51 microgL-1, with maximum response measured within 25 minutes and inhibition being accompanied by a large decrease in fluorescence yield. The potential for this C. vulgaris-based bioassay to be used for the detection of copper is discussed. There was no evidence that the standard ToxY-PAM protocol, using these unicellular algae species, could be used for the detection of chlorpyrifos or nonylphenol ethoxylate at environmentally relevant levels.

The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro
Cole, G. W., Jr., A. M. Alleva, et al. (2005), J Thorac Cardiovasc Surg 129(5): 1010-7.
Abstract: OBJECTIVE: Malignant pleural mesothelioma is notoriously refractory to aggressive multimodality therapy. Epidermal growth factor receptor expression has been observed on malignant pleural mesothelioma cells. Epidermal growth factor receptor-mediated signaling promotes tumorigenesis and metastasis of cancer cells. The purpose of this study is to evaluate the ability of the epidermal growth factor receptor tyrosine kinase inhibitor PD153035 to abrogate the expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. METHODS: Epidermal growth factor receptor expression of malignant pleural mesothelioma cells and primary normal cells was quantitated by means of flow cytometry. PD153035-mediated growth inhibition was determined by means of 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan and clonogenic assays. Cell motility and invasion of extracellular matrix was evaluated with in vitro wound-healing and Matrigel invasion assays, respectively. Vascular epidermal growth factor levels in conditioned media were measured by using enzyme-linked immunosorbent assay. RESULTS: Epidermal growth factor receptor expression was detected on all 6 cultured malignant pleural mesothelioma cells, with 4 of 6 having normal receptor expression and 2 of 6 overexpressing the receptor. PD153035 suppressed cell motility and cell invasion through a Matrigel membrane, regardless of the baseline epidermal growth factor receptor expression. Decreased vascular epidermal growth factor production and significant inhibition of growth only occurred in malignant pleural mesothelioma cells that overexpress epidermal growth factor receptor. CONCLUSIONS: Epidermal growth factor receptor tyrosine kinase inhibitor PD153035 significantly inhibited motility and invasion in malignant pleural mesothelioma cells in vitro, regardless of their epidermal growth factor receptor expression levels. Inhibition of epidermal growth factor receptor-dependent signaling might be a useful strategy to diminish malignant pleural mesothelioma recurrence after aggressive cytoreductive surgery.

The self-setting properties and in vitro bioactivity of tricalcium silicate
Zhao, W., J. Wang, et al. (2005), Biomaterials 26(31): 6113-21.
Abstract: In this study, tricalcium silicate (Ca(3)SiO(5)), as a new promising injectable bioactive material, was employed to investigate its physical and chemical properties for an injectable bioactive cement filler. The workable Ca(3)SiO(5) pastes with a liquid to powder (L/P) ratio of 0.8--.2 mlg(-1)could be injected for 15--60 min (nozzle diameter 2.0mm). The setting process yielded cellular structures with compressive strength of 6.4--20.2 MPa after 2--28 days. The in vitro bioactivity of Ca(3)SiO(5) paste was investigated by soaking in simulated body fluid (SBF) for various periods. The result showed that the Ca(3)SiO(5) paste could induce hydroxyapatite (HA) formation and dissolve slowly in SBF. The result of indirect cytotoxicity evaluation indicated that Ca(3)SiO(5) paste had a stimulatory effect on cell growth in a certain concentration range. The exothermic process showed that Ca(3)SiO(5) had lower heat evolution rate during the hydration as compared to calcium phosphate cement (CPC). Our results indicated that Ca(3)SiO(5) paste was bioactive and dissolvable, and it is a progressive candidate for further investigation as injectable tissue repairing substitute.

The separation of catalyst after photocatalytic reactions conducted in the presence of TiO2/FeCl3/UV
Baran, W., A. Makowski, et al. (2005), Chemosphere 59(6): 853-9.
Abstract: One of the problems connected with wastewater treatment by the photocatalytic method in the presence of TiO2 suspension is necessity of the later catalyst separation. The method proposed by us for this purpose, consists in the usage of coagulation of TiO2 suspension with the aid of FeCl3, particularly in the cases when addition of the salt is used in order to intensification of the photocatalytic process. The effects of the TiO2 separation were studied from the mixtures, after photocatalytic Acid Orange 7 degradation, with dosage of FeCl3 at different stages of the process. The coagulation was carried out at different pH values as well as different FeCl3 concentrations. It was stated that nearly 100% of separation and simultaneously, nearly 100% of decolouration of the examined Acid Orange 7 solutions after their illumination in the presence of TiO2/FeCl3 and coagulation which was produced only by increasing of pH of the obtained mixtures, were nearly possible.

The signaling network of transforming growth factor beta1, protein kinase Cdelta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells
Lee, M. S., T. Y. Kim, et al. (2005), Mol Cell Biol 25(16): 6921-36.
Abstract: Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor beta1 (TGFbeta1) pathway that is mediated by protein kinase Cdelta (PKCdelta). TGFbeta1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKCdelta, which is required for expression and activation of integrins. Increased expression of integrins alpha2 and alpha3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGFbeta1 effects. Furthermore, TGFbeta1 treatment and PKCdelta activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGFbeta pathway, PKCdelta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.

The significance of infection related to orthopedic devices and issues of antibiotic resistance
Campoccia, D., L. Montanaro, et al. (2006), Biomaterials 27(11): 2331-9.
Abstract: Over the last 15 years, with the advent of modern standards in the control of sterility within the operating room environment and adequate protocols of peri-operative antibiotic prophylaxis, the incidence of infections associated to orthopedic implants has become very low. Nevertheless, the event of infection still represents one of the most serious and devastating complications which may involve prosthetic devices. It leads to complex revision procedures and, often, to the failure of the implant and the need for its complete removal. In orthopedics, for the enormous number of surgical procedures involving invasive implant materials, even if nowadays rare, infections have a huge impact in terms of morbidity, mortality, and medical costs. The difficult battle to prevent and fight bacterial infections associated to prosthetic materials must be played on different grounds. A winning strategy requires a clear view of the pathogenesis and the epidemiology of implant-related infections, with a special attention on the alarming phenomenon of antibiotic resistance. In this regard staphylococci are the prevalent and most important causative pathogens involved in orthopedic implant-related infections, and, thus, the main enemy to defeat. In this paper, we offer an overview of the complexity of this battleground and of the current and new, in our opinion most promising, strategies in the field of biomaterials to reduce the risks and counteract the establishment of implant infections.

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