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ABSTRACT: Nanopatterns on titanium may enhance endosseous implant biofunctionality. To enable biological studies to prove this hypothesis, we developed a scalable method of fabricating nanogrooved titanium substrates. We defined nanogrooves by nanoimprint lithography (NIL) and a subsequent pattern transfer to the surface of ASTM grade 2 bulk titanium applying a soft-mask for chlorine-based reactive ion etching (RIE). With respect to direct write lithographic techniques the method introduced here is fast and capable of delivering uniformly patterned areas of at least 4 cm(2). A dedicated silicon nanostamp process has been designed to generate the required thickness of the soft-mask for the NIL-RIE pattern transfer. Stamps with pitch sizes from 1000 nm down to 300 nm were fabricated using laser interference lithography (LIL) and deep cryogenic silicon RIE. Although silicon nanomachining was proven to produce smaller pitch sizes of 200 nm and 150 nm respectively, successful pattern transfer to titanium was only possible down to a pitch of 300 nm. Hence, the smallest nanogrooves have a width of 140 nm. An x-ray photoelectron spectroscopy study showed that only very few contaminations arise from the fabrication process and a cytotoxicity assay on the nanopatterned surfaces confirmed that the obtained nanogrooved titanium specimens are suitable for in vivo studies in implantology research.
Nanotechnology 02/2012; 23(6):065306. · 3.98 Impact Factor
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ABSTRACT: Organised nanotopography mimicking the natural extracellular matrix can be used to control morphology, cell motility, and differentiation. However, it is still unknown how specific cell types react with specific patterns. Both initial adhesion and preferential cell migration may be important to initiate and increase cell locomotion and coverage with cells, and thus achieve an enhanced wound healing response around an implantable material. Therefore, the aim of this study was to evaluate how MC3T3-E1 osteoblast initial adhesion and directional migration are influenced by nanogrooves with pitches ranging from 150 nm up to 1000 nm. In this study, we used a multi-patterned substrate with five different groove patterns and a smooth area with either a concentric or radial orientation. Initial cell adhesion measurements after 10 s were performed using atomic force spectroscopy-assisted single-cell force spectroscopy, and demonstrated that nascent cell adhesion was highly induced by a 600 nm pitch and reduced by a 150 nm pitch. Addition of RGD peptide significantly reduced adhesion, indicating that integrins and cell adhesive proteins (e.g. fibronectin or vitronectin) are key factors in specific cell adhesion on nanogrooved substrates. Also, cell migration was highly dependent on the groove pitch; the highest directional migration parallel to the grooves was observed on a 600 nm pitch, whereas a 150 nm pitch restrained directional cell migration. From this study, we conclude that grooves with a pitch of 600 nm may be favourable to enhance fast wound closure, thereby promoting tissue regeneration.
European cells & materials 01/2012; 23:182-93; discussion 193-4. · 3.03 Impact Factor
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ABSTRACT: During the installation of implants, osteogenic bone particles are translocated along the surface. These particles may contribute to peri-implant bone healing. Based on this phenomenon, it is hypothesized that implants placed with undersized drilling, besides showing higher primary-implant stability, also enhance the amount and osteogenic responses of these bone particles. Biocomp implants were inserted into bicortical fresh-cadaver bone by a press-fit or an undersized surgical technique, and peak-insertion torque values (ITV) were measured. After explantation, the implants were incubated in culture medium up to 24 days. Histology, bone-implant contact (BIC), micro-CT, scanning electron microscopy (SEM), and calcium (Ca) measurements were performed. ITV were significantly higher for implants placed with an undersized technique. Moreover, histology, BIC, micro-CT, SEM, and Ca measurements confirmed the presence of more bone-like tissue on implants inserted with an undersized technique. The undersized surgical technique not only results in higher primary-implant stability, but also induces more translocated bone particles, thus having a positive influence on the osteogenic response.
Journal of dental research 03/2010; 89(6):581-6. · 3.46 Impact Factor
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ABSTRACT: The natural environment of a living cell is not only organized on a micrometer, but also on a nanometer scale. Mimicking such a nanoscale topography in implantable biomaterials is critical to guide cellular behavior. Also, a correct positioning of cells on biomaterials is supposed to be very important for promoting wound healing and tissue regeneration. The exact mechanism by which nanotextures can control cellular behavior are thus far not well understood and it is thus far unknown how cells recognize and respond to certain surface patterns, whereas a directed response appears to be absent on other pattern types. Focal adhesions (FAs) are known to be involved in the process of specific pattern recognition and subsequent response by cells. In this study, we used a high throughput screening "Biochip" containing 40 different nanopatterns to evaluate the influence of several nanotopographical cues like depth, width, (an)isotropy and spacing (ridge-groove ratio) on osteoblast behavior. Microscopical analysis and time lapse imaging revealed that an isotropic topography did not alter cell morphology, but it highly induced cell motility. Cells cultured on anisotropic topographies on the other hand, were highly elongated and aligned. Time-lapse imaging revealed that cell motility is highly dependent on the ridge-groove ratio of anisotropic patterns. The highest motility was observed on grooves with a ratio of 1:3, whereas the lowest motility was observed on ratios of 1:1 and 3:1. FA measurements demonstrated that FA-length decreased with increasing motility. From the study it can be concluded that osteoblast behavior is tightly controlled by nanometer surface features.
European cells & materials 01/2010; 20:329-43. · 3.03 Impact Factor
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ABSTRACT: COLLOSS E, an equine extracellular matrix product containing native transforming growth factor beta1 and several bone morphogenetic proteins, has shown osteoinductive properties in ectopic sites. This study was set up to examine its properties in an orthotoptic site in conjunction with a beta-tricalciumphosphate (beta-TCP) scaffolding material. Thirty-two 17-mm circular defects in goat mandibles were filled with COLLOSS E, beta-TCP, COLLOSS E + beta-TCP, or left empty. After 9 weeks the results were quantified by micro-computed tomography and histology. The empty defects contained the highest percentage of new bone (62%). The beta-TCP scaffold resulted in 38% (p = 0.0029), the mixture of beta-TCP/COLLOSS E resulted in 36% (p = 0.0057), while the use of COLLOSS E alone resulted in 55% (not significant p = 0.34). These results show that addition of TCP did not result in the expected synergy with regard to the healing of the defect and seemed even to inhibit the healing process. On the other hand, the addition of COLLOSS E induced the formation of small islands of new bone, not connected to the defect edges. This was not observed in the specimens not containing COLLOSS E (4.61% of bone formation centrally in the defect vs. 0.56%; p = 0.042). In conclusion, the results of the present study are somewhat unexpected in that the empty defects showed the most bone ingrowth; however, this ingrowth was always connected to the defect edges. In contrast, the application of COLLOSS E with or without beta-TCP induced bone formation in the center of the defects also.
Journal of Biomedical Materials Research Part B Applied Biomaterials 12/2009; 92(2):517-24. · 2.15 Impact Factor
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ABSTRACT: Previously, in vitro differentiation of odontoblasts was shown for dental pulp stem cells (DPSCs) transfected with bone morphogenetic protein-2 (Bmp2). For this study, we hypothesized that such cells also show potential for mineralized tissue formation in vivo. DPSCs were transfected with Bmp2 and seeded onto a ceramic scaffold. These complexes were cultured in medium without dexamethasone, and thereafter placed subcutaneously in nude mice for 1, 4, and 12 weeks. Samples were evaluated by histology and real-time PCR for osteocalcin, bone sialoprotein, dentin sialophosphoprotein, and dentin matrix protein 1. Results indicated that only the transfected DPSCs showed obvious mineralized tissue generation, and 12 weeks of implantation gave the highest percentage of mineralized tissue formation (33 +/- 7.3% of implant pore area). Real-time PCR confirmed these results. In conclusion, Bmp2-transfected DPSCs effectively show mineralized tissue formation upon ectopic implantation.
Journal of dental research 11/2009; 88(11):1020-5. · 3.46 Impact Factor
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ABSTRACT: In this study, the growth factors in COLLOSSE were analyzed, using ELISA tests, mass spectrometry, western blotting, and a 24-day cell culture experiment using osteoblast-like cells. The results of the ELISA testing, mass spectrometry, and western blotting all confirmed that TGF-beta1 was the main growth factor in COLLOSSE at 55 ng/mg. The results from the culture test showed that the cell proliferation, alkaline phosphatase activity, and matrix calcification were all drastically changed by the addition of COLLOSSE, mirroring the effects of addition of TGF-beta1. We conclude that COLLOSSE is not only a rich source of TGFbeta-1, but also contains the growth factors TGFbeta-2, BMP-2, BMP-3, BMP-7, IGF-1, and possibly VEGF. Other growth factors might be present in COLLOSSE, but were not identified due to inherent detection limits of the used ELISA and mass spectrometry techniques. The number of osteoinductive factors in COLLOSSE causes a synergistic effect, explaining the new bone formation found in previously described in vivo studies, with much lower growth factor concentrations when compared with recombinant BMPs.
Journal of Biomedical Materials Research Part B Applied Biomaterials 06/2009; 89(2):300-5. · 2.15 Impact Factor
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ABSTRACT: In this study, the growth factors in COLLOSS®E were analyzed, using ELISA tests, mass spectrometry, western blotting, and a 24-day cell culture experiment using osteoblast-like cells. The results of the ELISA testing, mass spectrometry, and western blotting all confirmed that TGF-β1 was the main growth factor in COLLOSS®E at 55 ng/mg. The results from the culture test showed that the cell proliferation, alkaline phosphatase activity, and matrix calcification were all drastically changed by the addition of COLLOSS®E, mirroring the effects of addition of TGF-β1. We conclude that COLLOSS®E is not only a rich source of TGFβ-1, but also contains the growth factors TGFβ-2, BMP-2, BMP-3, BMP-7, IGF-1, and possibly VEGF. Other growth factors might be present in COLLOSS®E, but were not identified due to inherent detection limits of the used ELISA and mass spectrometry techniques. The number of osteoinductive factors in COLLOSS®E causes a synergistic effect, explaining the new bone formation found in previously described in vivo studies, with much lower growth factor concentrations when compared with recombinant BMPs. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Journal of Biomedical Materials Research Part B Applied Biomaterials 04/2009; 89B(2):300 - 305. · 2.15 Impact Factor
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ABSTRACT: Up to the present time, bone transplants are commonly used to reconstruct bone defects. Recently, several bone substitutes have been suggested to overcome the disadvantages of the procedure of bone harvesting. However, research reveals that an autogenous bone graft is still the gold standard. To replicate the structure and function of natural bone, growth factors or even living, bone-forming cells can be added to enhance the formation of new bone. In that case, one speaks of cell-based tissue-substition. As an alternative distraction osteogenesis, a mechanical-based way of tissue engineering is suggested. In this procedure, tissue-generation takes place without the addition of external material. A combination of both tissue-substitution techniques, consisting of the addition of bone-replacement materials or growth factors during distraction osteogenesis, has also been evaluated in research on animals, although not with unequivocal results.
Nederlands tijdschrift voor tandheelkunde 07/2008; 115(6):297-304.
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ABSTRACT: This study was designed to examine the influence of integrin subunit-beta1 and subunit-beta3 on the behavior of primary osteoblast-like cells, cultured on calcium phosphate (CaP)-coated and non coated titanium (Ti). Osteoblast-like cells were incubated with specific monoclonal antibodies against integrin-beta1 and integrin-beta3 to block the integrin function. Subsequently, cells were seeded on Ti discs, either non coated or provided with a 2 microm carbonated hydroxyapatite coating using Electrostatic Spray Deposition. Results showed that on CaP coatings, cellular attachment was decreased after a pre-treatment with either anti-integrin-beta1 or anti-integrin-beta3 antibodies. On Ti, cell adhesion was only slightly affected after a pre-treatment with anti-integrin-beta3 antibodies. Scanning electron microscopy showed that on both types of substrate, cellular morphology was not changed after a pre-treatment with either antibody. With quantitative PCR, it was shown for both substrates that mRNA expression of integrin-beta1 was increased after a pre-treatment with either anti-integrin-beta1 or anti-integrin-beta3 antibodies. Furthermore, after a pre-treatment with either antibody, mRNA expression of integrin-beta3 and ALP was decreased, on both types of substrate. In conclusion, osteoblast-like cells have the ability to compensate to great extent for the blocking strategy as applied here. Still, integrin-beta1 and beta3 seem to play different roles in attachment, proliferation, and differentiation of osteoblast-like cells, and responses on CaP-coated substrates differ to non coated Ti. Furthermore, the influence on ALP expression suggests involvement of both integrin subunits in signal transduction for cellular differentiation.
Journal of Materials Science Materials in Medicine 03/2008; 19(2):861-8. · 2.32 Impact Factor
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ABSTRACT: This study evaluated in vitro the differences in morphological behaviour between fibroblast cultured on smooth and microgrooved substrata (groove depth: 0.5 mum, width: 1 mum), which were subjected to simulated microgravity. The aim of the study was to clarify which of these parameters was more dominant to determine cell behaviour. Morphological characteristics were investigated using scanning electron microscopy and fluorescence microscopy in order to obtain qualitative information on cell alignment. Expression of collagen type I, and alpha1-, beta1-, beta3-integrin were investigated by QPCR. Finally, immunoblotting was applied to visualise MAPK signalling pathways. Microscopy and image analysis showed that the fibroblasts aligned along the groove direction on all textured surfaces. On the smooth substrata, cells had spread out in a random fashion. The alignment of cells cultured on grooved surfaces under simulated microgravity, after 48 h of culturing appeared similar to those cultured at 1g, although cell shape was different. Analysis of variance proved that all main parameters: topography, gravity force, and time were significant. In addition, gene levels were reduced by simulated microgravity particularly those of beta3-integrin and collagen, however alpha-1 and beta-1 integrin levels were up-regulated. ERK1/2 was reduced in RPM, however, JNK/SAPK and p38 remained active. The members of the small GTPases family were stimulated under microgravity, particularly RhoA and Cdc42. The results are in agreement that application of microgravity to fibroblasts promotes a change in their morphological appearance and their expression of cell-substratum proteins through the MAPK intracellular signalling pathways.
Cell Motility and the Cytoskeleton 03/2008; 65(2):116-29. · 4.19 Impact Factor
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ABSTRACT: Nano-scale pattern templates have been manufactured in order to study the differences in cell behaviour between fibroblasts cultured on smooth and on grooved substrata. The pattern templates were made on silicon wafers using electron beam lithography in hydrogen silsesquioxane (HSQ) and subsequent reactive ion etching (RIE). These masters were replicated in polystyrene cell culture material using solvent casting. The replicas were assessed with atomic force microscopy (AFM). After seeding with fibroblasts, morphological charac-teristics were investigated using scanning electron microscopy (SEM) and light microscopy, in order to obtain qualitative and quantita-tive information on cell alignment. It appears that both groove depth and width determine the cellular alignment on patterns with a ridge/groove ratio of 1:1. On smooth substrata, cells always spread out in a random fashion. There appears to be a threshold groove barrier size of around 70–80 nm, above which random cell spreading is not possible anymore and contact guidance occurs. It is specu-lated that this threshold size may be associated with the size of contact molecules at the cell extensions, which grow and find anchoring spots preceding cell spread out and cell alignment.
02/2008;
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ABSTRACT: The aim of this study was to evaluate potential effects of DNA-coatings on calcium phosphate (CaP) nucleation from simulated body fluids (SBF) and subsequently the effects of DNA-coatings and SBF-immersed DNA coatings on the behavior of osteoblast-like cells. DNA-coatings demonstrated to enhance the nucleation and deposition of Cap from SBF compared to titanium controls. The behavior of osteoblast-like cells was affected on SBF-immersed DNA-coatings, showing an increased deposition of the extracellular matrix protein osteocalcin compared to titanium controls. These results indicate bone-bonding capacity of DNA-coatings, which needs to be confirmed using future animal experiments.
01/2008: pages 605-608;
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ABSTRACT: This study investigated the combined application of Transforming Growth Factor beta-1 (TGFbeta-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate osteogenic expression in vitro. TGFbeta-1 and BMP-2 fulfill specific roles in the formation of new bone. COLLOSS E, a bone-derived collagen product containing a variety of naturally occurring growth factors, was also used. Growth factors were administered to osteoblast-like cells from rat bone marrow (RBM). Proliferation and differentiation were monitored up to 24 days, by measuring total DNA content, alkaline phosphatase activity, and calcium content. Genetic expression of a set of differentiation markers at day 7 was measured by Q-PCR. Adding BMP-2 alone induced high proliferation rates, compared to the growth factor supplemented groups, and it induced high differentiation rates, compared to the control group. Adding TGFbeta-1 combined with BMP-2, TGFbeta-1 alone, or COLLOSS E resulted in a significant decrease in proliferation rate, but an increase in differentiation rate, compared to the control group. Additive or synergistic effects of application of TGFbeta-1 and BMP-2 were not observed. The observed effects of COLLOSS E mainly resembled those of TGFbeta-1 application alone. It can be concluded that BMP-2 is the most suitable candidate for osteogenic stimulation of RBM cells in these settings.
Journal of Biomedical Materials Research Part A 12/2007; 86(3):788-95. · 2.63 Impact Factor
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ABSTRACT: The differences in morphological behaviour between fibroblasts cultured on smooth and nanogrooved substrata (groove depth: 5-350 nm, width: 20-1000 nm) have been evaluated in vitro. The aim of the study was to clarify to what extent cell guidance occurs on increasingly smaller topographies. Pattern templates were made using electron beam lithography, and were subsequently replicated in polystyrene cell culture material using solvent casting. The replicates were investigated with atomic force microscopy (AFM). After seeding with fibroblasts, morphological characteristics were investigated using scanning electron microscopy (SEM) and light microscopy, in order to obtain qualitative and quantitative information on cell alignment. AFM revealed that the nanogroove/ridge widths were replicated perfectly, although at deeper levels the grooves became more concave. The smooth substrata had no distinguishable pattern other than a roughness amplitude of 1 nm. Interestingly, microscopy and image analysis showed that fibroblast after 4 h had adjusted their shape according to nanotopographical features down to cut-off values of 100 nm width and 75 nm depth. After 24 h culturing time, fibroblasts would even align themselves on groove depths as shallow as 35 nm. It appears depth is the most essential parameter in cellular alignment on groove patterns with a pitch ratio of 1:1. On the smooth substrata, cells always spread out in a random fashion. Analysis of variance (ANOVA) demonstrated that both main parameters, topography and culturing time, were significant. We conclude that fibroblast cells cultured on nanotopography experience a threshold feature size of 35 nm, below this value contact guidance does no longer exist.
Biomaterials 10/2007; 28(27):3944-51. · 7.40 Impact Factor
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ABSTRACT: This study investigated whether a novel ionogenic substance, containing amongst others zinc and rubidium (PHI-5; Dermagenics Inc, Memphis, TN, USA), could improve the healing of full-thickness skin wounds. Uniform wounds were created on the right flank of guinea pigs. Micro-grooved silicone rubber membranes, containing 0 (controls), 1.25, 5.00, or 10.00 microg PHI-5, were sutured onto this wound. Standardized digital wound photographs were made after 1, 3, and 6 weeks. Also, wound biopsies were taken after 3 and 6 weeks for histological and histomorphometrical evaluation. For all study groups, 6 animals were used. Analysis of the 1-week digital photographs showed that the surface area of the wounds decreased significantly, with an increasing PHI-5 concentration. No other differences were found in the wound photographs. Also, no differences were measured in histomorphometry at 3 and 6 weeks. Concluding, in our study model a single application of PHI-5 did have a significant positive influence on initial wound healing.
Journal of Materials Science Materials in Medicine 08/2007; 18(7):1449-56. · 2.32 Impact Factor
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ABSTRACT: This study describes the effect of multilayered DNA coatings on (i) the formation of mineralized depositions from simulated body fluids (SBF); and (ii) osteoblast-like cell behavior with and without pretreatment in SBF. DNA coatings were generated using electrostatic self-assembly, with poly-d-lysine or poly(allylamine hydrochloride) as cationic polyelectrolytes, on titanium substrates. Coated substrates and non-coated controls were immersed in SBF with various compositions. The deposition of calcium phosphate was enhanced on multilayered DNA coatings as compared with non-coated controls, and was dependent on the type of cationic polyelectrolyte used in the build-up of the DNA coatings. Further analysis showed that the depositions consisted of carbonated apatite. Non-pretreated DNA coatings were found to have no effect on osteoblast-like cell behavior compared with titanium controls. On the other hand, SBF-pretreatment of DNA coatings affected the differentiation of osteoblast-like cells through an increased deposition of osteocalcin. The results of this study are indicative of the bone-bonding capacities of DNA coatings. Nevertheless, future animal experiments are required to provide conclusive evidence for the bioactivity of DNA coatings.
Acta Biomaterialia 08/2007; 3(4):587-96. · 4.86 Impact Factor
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ABSTRACT: This study was performed to evaluate the basic biological response to deoxyribonucleic acid (DNA)-based coatings for soft tissue implants. To that end, in vitro experiments were used to study their cytocompatibility, and in vivo subcutaneous implantation studies with transponders in a rat model were performed to evaluate their histocompatibility. The DNA-based coatings were fabricated using the electrostatic self-assembly technique using cationic poly-D-lysine or poly-allylamine hydrochloride and anionic DNA. Noncoated substrates served as controls. In vitro, the behavior of primary rat dermal fibroblasts was assessed in terms of cell proliferation and morphology. Both types of multilayered DNA-coatings significantly increased rat dermal fibroblast proliferation without altering the morphological appearance of the cells. The tissue response to multilayered DNA-coatings was assessed using an in vivo rat model, in which transponders were inserted subcutaneously for 4 and 12 weeks. No macroscopic signs of inflammation or adverse tissue reactions were observed at implant retrieval. Histological analyses demonstrated a uniform tissue response to all types of implants. All implants were encapsulated in a fibrous tissue capsule without intervening inflammatory cells at the implant surface. Histomorphometrically, multilayered DNA-coatings induced fibrous tissue capsules with similar quality and thickness compared to noncoated controls. In addition, all fibrous tissue capsules showed similar expression of alpha-smooth muscle actin. This study demonstrates that multilayered DNA-coatings are cytocompatible and histocompatible, and justifies further research on their functionalization with biologically active compounds to modulate tissue responses.
Journal of Biomedical Materials Research Part B Applied Biomaterials 05/2007; 81(1):231-8. · 2.15 Impact Factor
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ABSTRACT: A pivotal factor to consider in the development of biomaterials and biomaterial coatings is the inflammatory response to these materials. The insertion of implants is followed by protein adsorption and subsequent interactions with cellular components of the biological surroundings, in which macrophages play a dominant role through the production of a myriad of signaling molecules. In view of this, the aims of the present study were to evaluate (i) gross protein adsorption to, and (ii) in vitro behavior of macrophages on novel biomaterial coatings, composed of poly-D-lysine (PDL) or poly(allylamine hydrochloride) (PAH) and DNA, and to compare these coatings with negative (noncoated glass) and positive controls (noncoated glass + LPS-stimulation). The results demonstrate that multilayered DNA-coatings do not affect gross protein adsorption compared to noncoated controls. Cell culture experiments showed that the attachment to, and viability and morphology of two types of macrophages cultured on multilayered DNA-coatings is comparable to noncoated controls. Still, macrophages repeatedly showed decreased secretion levels of the proinflammatory cytokine TNF-alpha on multilayered DNA-coatings, whereas no differences were observed in the secretion of IL-1beta, IL-10, and TGF-beta1. Appropriate animal studies are required to elucidate if these in vitro indications have clinical effects on the inflammatory and wound healing processes around implants.
Journal of Biomedical Materials Research Part A 04/2007; 80(3):612-20. · 2.63 Impact Factor
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ABSTRACT: This study evaluated in vitro the differences in morphological behaviour between fibroblast cultured on smooth and microgrooved substrata (groove depth: 0.5 microm, width: 1, 2, 5, and 10 microm), which were subjected to simulated microgravity. The aim of the study was to clarify which of these parameters was more dominant to determine cell behaviour. Morphological characteristics were investigated using scanning electron microscopy and fluorescence microscopy in order to obtain qualitative information on cell alignment and area. Confocal laser scanning microscopy visualised distribution of actin filaments and focal adhesion points. Finally, expression of collagen type I, fibronectin, and alpha1- and beta1-integrin were investigated by PCR. Microscopy and image analysis showed that the fibroblasts aligned along the groove direction on all textured surfaces. On the smooth substrata, cells had spread out in a random fashion. The alignment of cells cultured on grooved surfaces decreased under simulated microgravity, especially after 24 h of culturing. Cell surface area on grooved substrata were significantly smaller than on smooth substrata, but simulated microgravity on the grooved groups resulted in an enlargement of cell area. ANOVA was performed on all main parameters: topography, gravity force, and time. In this analysis, all parameters proved significant. In addition, gene levels were reduced by microgravity particularly those of beta1-integrin and fibronectin. From our data it is concluded that the fibroblasts primarily adjust their shape according to morphological environmental cues like substratum surface whilst a secondary, but significant, role is played by microgravity conditions.
Cell Motility and the Cytoskeleton 04/2007; 64(3):174-85. · 4.19 Impact Factor
