| 1. |
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| 2. |
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| 3. |
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| 4. |
- Ballo, Ahmed, 1978, et al.
(författare)
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Nanostructured model implants for in vivo studies: influence of well-defined nanotopography on de novo bone formation on titanium implants
- 2011
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Ingår i: International Journal of Nanomedicine. - 1178-2013 .- 1176-9114. ; 6, s. 3415-28
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Tidskriftsartikel (refereegranskat)abstract
- An implantable model system was developed to investigate the effects of nanoscale surface properties on the osseointegration of titanium implants in rat tibia. Topographical nanostructures with a well-defined shape (semispherical protrusions) and variable size (60 nm, 120 nm and 220 nm) were produced by colloidal lithography on the machined implants. Furthermore, the implants were sputter-coated with titanium to ensure a uniform surface chemical composition. The histological evaluation of bone around the implants at 7 days and 28 days after implantation was performed on the ground sections using optical and scanning electron microscopy. Differences between groups were found mainly in the new bone formation process in the endosteal and marrow bone compartments after 28 days of implantation. Implant surfaces with 60 nm features demonstrated significantly higher bone-implant contact (BIC, 76%) compared with the 120 nm (45%) and control (57%) surfaces. This effect was correlated to the higher density and curvature of the 60 nm protrusions. Within the developed model system, nanoscale protrusions could be applied and systematically varied in size in the presence of microscale background roughness on complex screw-shaped implants. Moreover, the model can be adapted for the systematic variation of surface nanofeature density and chemistry, which opens up new possibilities for in vivo studies of various nanoscale surface-bone interactions.
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| 5. |
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| 6. |
- Briand, Elisabeth, 1979, et al.
(författare)
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Chemical Modifications of Au/SiO2 Template Substrates for Patterned Biofunctional Surfaces
- 2011
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 27:2, s. 678-685
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to create patterned surfaces for localized and specific biochemical recognition. For this purpose, we have developed a protocol for orthogonal and material-selective surface modifications of microfabricated patterned surfaces composed of SiO2 areas (100 mu m diameter) surrounded by Au. The SiO2 spots were chemically modified by a sequence of reactions (silanization using an amine-terminated silane (APTES), followed by amine coupling of a biotin analogue and biospecific recognition) to achieve efficient immobilization of streptavidin in a functional form. The surrounding Au was rendered inert to protein adsorption by modification by HS(CH2)(10)CONH-(CH2)(2)(OCH2CH2)(7)OH (thiol-OEG). The surface modification protocol was developed by testing separately homogeneous SiO2 and Au surfaces, to obtain the two following results: (i) SiO2 surfaces which allowed the grafting of streptavidin, and subsequent immobilization of biotinylated antibodies, and (ii) Au surfaces showing almost no affinity for the same streptavidin and antibody solutions. The surface interactions were monitored by quartz crystal microbalance with dissipation monitoring (QCM-D), and chemical analyses were performed by polarization modulation-reflexion absorption infrared spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS) to assess the validity of the initial orthogonal assembly of APTES and thiol-OEG. Eventually, microscopy imaging of the modified Au/SiO2 patterned substrates validated the specific binding of streptavidin on the SiO2/APTES areas, as well as the subsequent binding of biotinylated anti-rIgG and further detection of fluorescent rIgG on the functionalized SiO2 areas. These results demonstrate a successful protocol for the preparation of patterned biofunctional surfaces, based on microfabricated Au/SiO2 templates and supported by careful surface analysis. The strong immobilization of the biomolecules resulting from the described protocol is advantageous in particular for micropatterned substrates for cell-surface interactions.
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| 7. |
- Briand, Elisabeth, 1979, et al.
(författare)
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Combined QCM-D and EIS study of supported lipid bilayer formation and interaction with pore-forming peptides
- 2010
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 135:2, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- A novel set-up combining the quartz crystal microbalance with dissipation monitoring technique (QCM-D) and electrochemical impedance spectroscopy (EIS) under flow conditions was successfully used to follow supported lipid bilayer (SLB) formation on SiO(2). This study demonstrates the simultaneous detection, in real time, of both the electrical and the structural properties of the SLB. The combination of the two techniques provided novel insights regarding the mechanism of SLB formation: we found indications for an annealing process of the lipid alkyl chains after the mass corresponding to complete bilayer coverage had been deposited. Moreover, the interaction of the SLB with the pore-forming toxin, gramicidin D (grD) was studied for grD concentrations ranging from 0.05 to 40 mg L(-1). Membrane properties were altered depending on the toxin concentration. For low grD concentrations, the electrical properties of the SLB changed upon insertion of active ion channels. For higher concentrations, the QCM-D data showed dramatic changes in the viscoelastic properties of the membrane while the EIS spectra did not change. AFM confirmed significant structural changes of the membrane at higher grD concentrations. Thus, the application of combined QCM-D and EIS detection provides complementary information about the system under study. This information will be particularly important for the continued detailed investigation of interactions at model membrane surfaces
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| 8. |
- Dahlbom, Sixten, et al.
(författare)
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Analysis of per- and polyfluoroalkyl substances (PFAS) extraction from contaminated firefighting materials: Effects of cleaning agent, temperature, and chain-length dependencies
- 2024
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Ingår i: Emerging Contaminants. - 2405-6650 .- 2405-6642. ; 10:3, s. 100335-100335
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Tidskriftsartikel (refereegranskat)abstract
- This investigation delves into the extraction dynamics of 22 per- and polyfluoroalkyl substances from PFAS contaminated firefighting materials. Two distinct test sets were executed: one contrasting a commercial product with water following an elaborate decontamination procedure, and the other assessing seven washing agents on materials from firefighting installations, with one agent examined at 22 °C and 50 °C. A general tendency for improved desorption at the higher temperature was observed. Furthermore, a discernible influence of the cleaning agent's pH on the extraction of specific PFAS species was observed, elucidating the role of chemical environment in the extraction process. PFAS rebound was studied for a period of up to 157 days, this unveiled a gradual escalation in PFAS22 levels, indicative of a protracted desorption mechanism. Intriguingly, PFAS with abbreviated carbon chains (C4–C6) exhibit superior desorption efficiency compared to their elongated congeners, suggesting a chain-length-dependent decontamination potential. A comparative scrutiny between a commercially available cleaning product, featuring multiple washing and flushing steps, and a water-only treatment regimen underscores the potential efficacy of the former. This exhaustive investigation furnishes nuanced insights into PFAS extraction complexities, offering a foundation for informed decontamination strategies
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| 9. |
- de Peppo, Giuseppe Maria, et al.
(författare)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 10. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 11. |
- Flys, Olena, 1971-, et al.
(författare)
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Applicability of characterization techniques on fine scale surfaces
- 2018
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Ingår i: Surface Topography: Metrology and Properties. - Bristol : Institute of Physics Publishing (IOPP). - 2051-672X. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- In this study, several surface topographies typical for dental implants were evaluated by different measurement techniques. The samples were prepared by machine turning, wet chemical etching and electrochemical polishing of titanium discs. The measurement techniques included an atomic force microscope (AFM), coherence scanning interferometer (CSI) and a 3D stereo scanning electron microscope (SEM). The aim was to demonstrate and discuss similarities and differences in the results provided by these techniques when analyzing submicron surface topographies. The estimated surface roughness parameters were not directly comparable since the techniques had different surface spatial wavelength band limits. However, the comparison was made possible by applying a 2D power spectral density (PSD) function. Furthermore, to simplify the comparison, all measurements were characterized using the ISO 25178 standard parameters. Additionally, a Fourier transform was applied to calculate the instrument transfer function in order to investigate the behavior of CSI at different wavelength ranges. The study showed that 3D stereo SEM results agreed well with AFM measurements for the studied surfaces. Analyzed surface parameter values were in general higher when measured by CSI in comparison to both AFM and 3D stereo SEM results. In addition, the PSD analysis showed a higher power spectrum density in the lower frequency range 10-2-10-1 μm-1 for the CSI compared with the other techniques.
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| 12. |
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| 13. |
- Granskog, Viktor, et al.
(författare)
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High-Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair
- 2018
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 28:26
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Tidskriftsartikel (refereegranskat)abstract
- The use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self-etch primers. Validation of the adhesive strength is conducted on wet bone substrates and accomplished via fiber-reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bond strength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K-wires and match metal plates and screw implants.
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| 14. |
- Håkansson, Joakim, 1975, et al.
(författare)
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Individualized tissue-engineered veins as vascular grafts: A proof of concept study in pig
- 2021
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 15:10, s. 818-830
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Tidskriftsartikel (refereegranskat)abstract
- Personalized tissue engineered vascular grafts are a promising advanced therapy medicinal product alternative to autologous or synthetic vascular grafts utilized in blood vessel bypass or replacement surgery. We hypothesized that an individualized tissue engineered vein (P-TEV) would make the body recognize the transplanted blood vessel as autologous, decrease the risk of rejection and thereby avoid lifelong treatment with immune suppressant medication as is standard with allogenic organ transplantation. To individualize blood vessels, we decellularized vena cava from six deceased donor pigs and tested them for cellular removal and histological integrity. A solution with peripheral blood from the recipient pigs was used for individualized reconditioning in a perfusion bioreactor for seven days prior to transplantation. To evaluate safety and functionality of the individualized vascular graft in vivo, we transplanted reconditioned porcine vena cava into six pigs and analyzed histology and patency of the graft at different time points, with three pigs at the final endpoint 4-5 weeks after surgery. Our results showed that the P-TEV was fully patent in all animals, did not induce any occlusion or stenosis formation and we did not find any signs of rejection. The P-TEV showed rapid recellularization in vivo with the luminal surface covered with endothelial cells. In summary, the results indicate that P-TEV is functional and have potential for use as clinical transplant grafts.
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| 15. |
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| 16. |
- Jenndahl, L., et al.
(författare)
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Personalized tissue-engineered arteries as vascular graft transplants : A safety study in sheep
- 2022
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Ingår i: Regenerative Therapy. - : Japanese Society of Regenerative Medicine. - 2352-3204. ; 21, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cardiovascular disease often need replacement or bypass of a diseased blood vessel. With disadvantages of both autologous blood vessels and synthetic grafts, tissue engineering is emerging as a promising alternative of advanced therapy medicinal products for individualized blood vessels. By reconditioning of a decellularized blood vessel with the recipient's own peripheral blood, we have been able to prevent rejection without using immunosuppressants and prime grafts for efficient recellularization in vivo. Recently, decellularized veins reconditioned with autologous peripheral blood were shown to be safe and functional in a porcine in vivo study as a potential alternative for vein grafting. In this study, personalized tissue engineered arteries (P-TEA) were developed using the same methodology and evaluated for safety in a sheep in vivo model of carotid artery transplantation. Five personalized arteries were transplanted to carotid arteries and analyzed for safety and patency as well as with histology after four months in vivo. All grafts were fully patent without any occlusion or stenosis. The tissue was well cellularized with a continuous endothelial cell layer covering the luminal surface, revascularized adventitia with capillaries and no sign of rejection or infection. In summary, the results indicate that P-TEA is safe to use and has potential as clinical grafts.
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| 17. |
- Jonsson, Magnus, 1981, et al.
(författare)
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Locally Functionalized Short-Range Ordered Nanoplasmonic Pores for Bioanalytical Sensing
- 2010
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 82:5, s. 2087-2094
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Tidskriftsartikel (refereegranskat)abstract
- Nanoplasmonic sensors based on short-range ordered nano-holes in thin metal films and discrete metal nanoparticles are known to provide similar sensing performance. However, a perforated metal film is unique in the sense that the holes can be designed to penetrate through the substrate, thereby also fulfilling the role of nanofluidic channels. This paper presents a bioanalytical sensing concept based on short-range ordered nanoplasmonic pores (diameter 150 nm) penetrating through a thin (around 250 nm) multilayer membrane composed of gold and silicon nitride (SiN) that is Supported on a Si wafer. Also, a fabrication scheme that enables parallel production of multiple (more than 50) separate sensor chips or more than 1000 separate nanoplasmonic membranes on it single wafer is presented. Together with the localization of the sensitivity to within such short-range ordered nanoholes, the structure provides it two-dimensional nanofluidic network, sized in the order of 100 x 100 mu m(2), with nanoplasmon active regions localized to each individual nanochannel. A material-specific surface-modification scheme was developed to promote specific binding of target molecules on the optically active gold regions only, while suppressing nonspecific adsorption on SiN. Using this protocol, and by monitoring the temporal variation in the plasmon resonance of the structure, we demonstrate flow-through nanoplasmonic sensing of specific biorecognition reactions with a signal-to-noise ratio of around 50 at a temporal resolution below 190 ms. With flow, the uptake was demonstrated to be at least 1 order of magnitude faster than under stagnant conditions, while still keeping the sample consumption at a minimum.
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| 18. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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Molecular Response to Nanopatterned Implants in the Human Jaw Bone
- 2021
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Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 7:12, s. 5878-5889
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Tidskriftsartikel (refereegranskat)abstract
- Implant surface modification by nanopatterning is an interesting route for enhancing osseointegration in humans. Herein, the molecular response to an intentional, controlled nanotopography pattern superimposed on screw-shaped titanium implants is investigated in human bone. When clinical implants are installed, additional two mini-implants, one with a machined surface (M) and one with a machined surface superimposed with a hemispherical nanopattern (MN), are installed in the posterior maxilla. In the second-stage surgery, after 6-8 weeks, the mini-implants are retrieved by unscrewing, and the implant-adherent cells are subjected to gene expression analysis using quantitative polymerase chain reaction (qPCR). Compared to those adherent to the machined (M) implants, the cells adherent to the nanopatterned (MN) implants demonstrate significant upregulation (1.8- to 2-fold) of bone-related genes (RUNX2, ALP, and OC). No significant differences are observed in the expression of the analyzed inflammatory and remodeling genes. Correlation analysis reveals that older patient age is associated with increased expression of proinflammatory cytokines (TNF-alpha and MCP-1) on the machined implants and decreased expression of proosteogenic factor (BMP-2) on the nanopatterned implants. Controlled nanotopography, in the form of hemispherical 60 nm protrusions, promotes gene expressions related to early osteogenic differentiation and osteoblastic activity in implant-adherent cells in the human jaw bone.
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| 19. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 136, s. 279-290
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Tidskriftsartikel (refereegranskat)abstract
- The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.
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| 20. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The influence of controlled surface nanotopography on the early biological events of osseointegration
- 2017
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 53, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- The early cell and tissue interactions with nanopatterned titanium implants are insufficiently described in vivo. A limitation has been to transfer a pre-determined, well-controlled nanotopography to 3D titanium implants, without affecting other surface parameters, including surface microtopography and chemistry. This in vivo study aimed to investigate the early cellular and molecular events at the bone interface with screw-shaped titanium implants superimposed with controlled nanotopography. Polished and machined titanium implants were firstly patterned with 75-nm semispherical protrusions. Polished and machined implants without nano-patterns were designated as controls. Thereafter, all nanopatterned and control implants were sputter-coated with a 30 nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12 h,1 d and 3 d. In one group, the implants were unscrewed and the implant-adherent cells were analyzed using quantitative polymerase chain reaction. In another group, implants with surrounding bone were harvested en bloc for histology and immunohistochemistry. The results showed that nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1), at 1 d, and triggered the expression of osteocalcin (DC) at 3 d. This was in parallel with a relatively lower number of recruited CD68-positive macrophages in the tissue surrounding the nanopatterned implants. Moreover, a higher proportion of newly formed osteoid and woven bone was found at the nanopatterned implants at 3 d. It is concluded that nanotopography, per se, attenuates the inflammatory process and enhances the osteogenic response during the early phase of osseointegration. This nanotopography-induced effect appeared to be independent of the underlying microscale topography. This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 21. |
- Karazisis, Dimitrios, et al.
(författare)
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The role of well-defined nanotopography of titanium implants on osseointegration : Cellular and molecular events in vivo
- 2016
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Ingår i: International Journal of Nanomedicine. - : Dove Medical Press Ltd.. - 1176-9114 .- 1178-2013. ; 11, s. 1367-1382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods: Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results: Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/μm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion: The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and osteoclastic (CatK) genes. Immunostaining and elemental analyses show higher osteogenic activity at the Nano implant. It is concluded that an implant with the present range of well-defined nanocues attenuates the inflammatory response while enhancing mineralization during osseointegration.
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| 22. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo
- 2016
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Ingår i: International Journal of Nanomedicine. - : Informa UK Limited. - 1178-2013 .- 1176-9114. ; 11, s. 1367-1381
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods: Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results: Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79 +/- 6 nm), and distribution (31 +/- 2 particles/mu m(2)). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-alpha, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion: The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-alpha) and osteoclastic (CatK) genes. Immunostaining and elemental analyses show higher osteogenic activity at the Nano implant. It is concluded that an implant with the present range of well-defined nanocues attenuates the inflammatory response while enhancing mineralization during osseointegration.
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| 23. |
- Knutsen, Maja, et al.
(författare)
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Oxygenated Nanocellulose - A Material Platform for Antibacterial Wound Dressing Devices
- 2021
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 4:10, s. 7554-7562
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Tidskriftsartikel (refereegranskat)abstract
- Both carboxylated cellulose nanofibrils (CNF) and dissolved oxygen (DO) have been reported to possess antibacterial properties. However, the combination for use as wound dressings against biofilm infections in chronic wounds is less known. The present study reports the development of oxygenated CNF dispersions that exhibit strong antibacterial effect. Carboxylated CNF dispersions with different oxidation levels were oxygenated by the OXY BIO System and tested for antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. The results reveal that the higher oxidation level of the CNFs, the better antibacterial effect. Scanning electron microscopy of bacterial biofilms revealed that a potential mechanism of action of the CNFs is the formation of a network surrounding and entrapping the bacteria. This effect is further potentiated by the oxygenation process. A CNF sample (concentration 0.6 wt %) that was oxygenated to a DO level of 46.4 mg/L demonstrated a strong antibacterial effect against S. aureus in vivo using a mouse model of surgical site infection. The oxygenated CNF dispersion reduced the bacterial survival by 71%, after 24 h treatment. The potent antibacterial effect indicates that oxygenated nanocellulose is a promising material for antibacterial wound dressings. © 2021 The Authors.
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| 24. |
- Kuna, Vijay Kumar, 1987, et al.
(författare)
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Significantly accelerated wound healing of full-thickness skin using a novel composite gel of porcine acellular dermal matrix and human peripheral blood cells
- 2017
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Ingår i: Cell Transplantation. - : Cognizant Communication Corporation. - 0963-6897 .- 1555-3892. ; 26:2, s. 293-307
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report the fabrication of a novel composite gel from decellularized gal-gal-knockout porcine skin and human peripheral blood mononuclear cells (hPBMC) for full-thickness skin wound healing. Decellularized skin extracellular matrix (ECM) powder was prepared via chemical treatment, freeze-drying and homogenization. The powder was mixed with culture medium containing hyaluronic acid to generate a pig skin gel (PSG). The effect of the gel in regeneration of full-thickness wound was studied in nude mice. We found significantly accelerated wound closure already on day 15 in animals treated with PSG only or PSG+hPBMC as compared to untreated and hyaluronic acid treated controls (p<0.05). Addition of the hPBMC to the gel resulted in marked increase of host blood vessels as well as the presence of human blood vessels. At day 25, histologically, the wounds in animals treated with PSG only or PSG+hPBMC were completely closed as compared to controls. Thus, the gel facilitated generation of new skin with well arranged epidermal cells and restored bilayer structure of the epidermis and dermis. These results suggest that porcine skin ECM gel together with human cells may be a novel and promising biomaterial for medical applications especially for patients with acute and chronic skin wounds.
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| 25. |
- Landberg, Göran, 1963, et al.
(författare)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
-
Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
-
Tidskriftsartikel (refereegranskat)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 26. |
- Landberg, Göran, et al.
(författare)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
-
Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 27. |
- Newman, Diane K, et al.
(författare)
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Intermittent catheterization with single- or multiple-reuse catheters : clinical study on safety and impact on quality of life
- 2020
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Ingår i: International Urology and Nephrology. - : Springer Science and Business Media LLC. - 0301-1623 .- 1573-2584. ; 19:1, s. 1-153
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Intermittent catheterization (IC) is a proven effective long-term bladder management strategy for individuals who have lower urinary tract dysfunction. This study provides clinical evidence about multiple-reuse versus single-use catheterization techniques and if catheter choice can have an impact on health-related quality of life (HRQoL).METHOD: A prospective, multi-center, clinical trial studied patients who currently practiced catheter reuse, and who agreed to prospectively evaluate single-use hydrophilic-coated (HC) (i.e. LoFric) catheters for 4 weeks. A validated Intermittent Self-Catheterization Questionnaire (ISC-Q) was used to obtain HRQoL. Reused catheters were collected and studied with regard to microbial and debris contamination.RESULTS: The study included 39 patients who had practiced IC for a mean of 10 years, 6 times daily. At inclusion, all patients reused catheters for a mean of 21 days (SD = 48) per catheter. 36 patients completed the prospective test period and the mean ISC-Q score increased from 58.0 (SD = 22.6) to 67.2 (SD = 17.7) when patients switched to the single-use HC catheters (p = 0.0101). At the end of the study, 83% (95% CI [67-94%]) preferred to continue using single-use HC catheters. All collected reused catheters (100%) were contaminated by debris and 74% (95% CI [58-87%]) were contaminated by microorganisms, some with biofilm.CONCLUSION: Single-use HC catheters improved HRQoL and were preferred over catheter reuse among people practicing IC. Catheter multiple-reuse may pose a potential safety concern due to colonization by microorganisms as well as having reduced acceptance compared to single use.TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT02129738.
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| 28. |
- Ohlsson, Gabriel, 1982, et al.
(författare)
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A miniaturized flow reaction chamber for use in combination with QCM-D sensing
- 2010
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Ingår i: Microfluidics and Nanofluidics. - : Springer Science and Business Media LLC. - 1613-4990 .- 1613-4982. ; 9:4-5, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- A miniaturized flow chamber for quartz crystal microbalance with dissipation monitoring (QCM-D) has been developed. The main purpose was to reduce the total liquid sample consumption during an experiment, but also to gain advantages with respect to kinetics and mass transport by reducing the boundary diffusion layer. The bottom of the flow chamber is a QCM-D sensor surface, on which a polydimethylsiloxane spacer ring, fabricated onto a poly(methyl methacrylate) lid, is placed symmetrically around the QCM-D electrode (diameter similar to 10 mm). The spacer ring defines the inner chamber height (typically 40-50 mu m) and provides sealing. Through the lid, there are inlet and outlet channels. The typical chamber volume is in the range of 2.5-3.5 mu l (with a 10 mu l dead volume). In flow mode, we have operated the cell at flow rates of 6-50 mu l/min, i.e., volume turnovers of 2-17 per min. As a model system, to test the microcell, the formation of supported phospholipid bilayers on a SiO2 surface was studied. For comparison, the same process was studied in a commercially available QCM-D equipment with significantly larger total volume (by a factor of 20). The decrease in effective sample consumption to produce a bilayer on the sensor surface in the chamber was approximately proportional to the decrease in chamber volume. Smaller volume also reduced the liquid exchange time. Potential improvements of the chamber include further optimization of the flow profile and, in addition, further miniaturization by decreasing the chamber height and the sensor radius.
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| 29. |
- Panagiotis Tasiopoulos, Christos, et al.
(författare)
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Surface Functionalization of PTFE Membranes Intended for Guided Bone Regeneration Using Recombinant Spider Silk
- 2020
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 3:1, s. 577-583
-
Tidskriftsartikel (refereegranskat)abstract
- Alveolar bone loss is usually treated with guided bone regeneration, a dental procedure which utilizes a tissue-separation membrane. The barrier membrane prevents pathogens and epithelial cells to invade the bone augmentation site, thereby permitting osteoblasts to deposit minerals and build up bone. This study aims at adding bioactive properties to otherwise inert PTFE membranes in order to enhance cell adherence and promote proliferation. A prewetting by ethanol and stepwise hydration protocol was herein employed to overcome high surface tension of PTFE membranes and allow for a recombinant spider silk protein, functionalized with a cell-binding motif from fibronectin (FN-silk), to self-assemble into a nanofibrillar coating. HaCaT and U-2 OS cells were seeded onto soft and hard tissue sides, respectively, of membranes coated with FN-silk. The cells could firmly adhere as early as 1 h post seeding, as well as markedly grow in numbers when kept in culture for 7 days. Fluorescence and scanning electron microscopy images revealed that adherent cells could form a confluent monolayer and develop essential cell-cell contacts during 1 week of culture. Hence, functionalized PTFE membranes have a potential of better integration at the implantation site, with reduced risk of membrane displacement as well as exposure to oral pathogens.
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| 30. |
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| 31. |
- Petronis, Sarunas, 1972
(författare)
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Functionalized Biomaterial Surfaces by Micro- and Nanofabrication
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the field of biomaterials, well-defined nano- and micropatterns or features at material surfaces can serve both as models for investigating material-biosystem interactions and as functional features for inducing, hindering or measuring specific bioreactions or biologic responses. Important bioreactions include protein adsorption and conformation, cell attachment and function, and adhesion and function of organized tissues or whole organisms. In this thesis, several studies are presented where the following functionalized materials have been micro- or nanopatterned and evaluated in biological systems: (1) Silicon substrates with patterned silver nanoparticles for probing biomolecule detection via SERS; (2) titania ceramic substrates with micro-cavities for culturing liver cells in vitro with preserved phenotype; (3) elastic silicone coatings with micro-pyramids and riblets to prevent marine biofouling by barnacle attachment; (4) silicon and epoxy model porous substrates containing interconnecting microchannels to investigate cell attachment and spreading as a function of substrate porosity; (5) silicon substrates with standing cantilevers for investigation of mechanical cell-substrate interactions. In all these studies, the main task was to achieve a well-controlled and systematic variation of the most relevant surface microscopic characteristics (chemical, topographical or mechanical), in order to tune or optimize the surfaces for their best functional performance, or to gain phenomenological understanding of how microscopic surface properties influence physical or biological interactions at surfaces. Electron beam lithography, photolithography and micro-replication techniques (such as injection molding, embossing and casting) were used to pattern biological test substrates on nanometer and micrometer length scales. Geometrical parameters and surface morphology of microfabricated surfaces were evaluated by scanning electron microscopy and stylus profilometry. Several surface sensitive techniques (x-ray photoelectron spectroscopy, Auger electron spectroscopy, secondary ion mass spectroscopy, contact angle measurements) were used to characterize chemical composition and wettability of the surfaces. Micromechanical characteristics of fabricated flexible structures were probed using atomic force microscopy in "force calibration" mode. It is demonstrated that the lithographic and replication methods used are excellent tools for preparing well-controlled micro- and nanopatterned surfaces in several materials. By systematically varying parameters of such patterns, mechanisms involved in such diverse areas as surface enhanced Raman scattering and marine biofouling have been proposed or verified. In addition, these patterning methods offer the possibility to design cell culture substrates that enhance the preservation of cell phenotype, or, alternatively, intentionally modify their behavior. The latter led to the discovery and development of a new way to measure and map the lateral forces exerted by cells on material surfaces in vitro.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Pfeiffer, Indriati, 1974, et al.
(författare)
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Vesicle Adsorption and Phospholipid Bilayer Formation on Topographically and Chemically Nanostructured Surfaces
- 2010
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 114:13, s. 4623-4631
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the influence of combined nanoscale topography and surface chemistry on lipid vesicle adsorption and supported bilayer formation on well-controlled model surfaces. To this end, we utilized colloidal lithography to nanofabricate pitted Au-SiO2 surfaces, where the top surface and the walls of the pits consisted of silicon dioxide whereas the bottom of the pits was made of gold. The diameter and height of the pits were fixed at 107 and 25 nm, respectively. Using the quartz crystal microbalance with dissipation monitoring (QCM-D) technique and atomic force microscopy (AFM), we monitored the processes occurring upon exposure of these nanostructured surfaces to a solution of extruded unilamellar 1-palmitolyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles with a nominal diameter of 100 nm. To scrutinize the influence of surface chemistry, we studied two cases: (1) the bare gold surface at the bottom of the pits and (2) the gold passivated by biotinamidocaproyl-labeled bovine serum albumin (BBSA) prior to vesicle exposure. As in our previous work on pitted silicon dioxide surfaces, we found that the pit edges promote bilayer formation on the SiO2 surface for the vesicle size used here in both cases. Whereas in the first case we observed a slow, continuous adsorption of intact vesicles onto the gold surface at the bottom of the pits, the presence of BBSA in the second case prevented the adsorption of intact vesicles into the pits. Instead, our experimental results, together with free energy calculations for various potential membrane configurations, indicate the formation of a continuous, supported lipid bilayer that spans across the pits. These results are significantly important for various biotechnology applications utilizing patterned lipid bilayers and highlight the power of the combined QCM-D/AFM approach to study the mechanism of lipid bilayer formation on nanostructured surfaces.
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| 36. |
- Rosendahl, Jennifer, et al.
(författare)
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3D printed nanocellulose scaffolds as a cancer cell culture model system
- 2021
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Ingår i: Bioengineering. - : MDPI AG. - 2306-5354. ; 8:7
-
Tidskriftsartikel (refereegranskat)abstract
- Current conventional cancer drug screening models based on two-dimensional (2D) cell culture have several flaws and there is a large need of more in vivo mimicking preclinical drug screening platforms. The microenvironment is crucial for the cells to adapt relevant in vivo characteristics and here we introduce a new cell culture system based on three-dimensional (3D) printed scaffolds using cellulose nanofibrils (CNF) pre-treated with 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO) as the structural material component. Breast cancer cell lines, MCF7 and MDA-MB-231, were cultured in 3D TEMPO-CNF scaffolds and were shown by scanning electron microscopy (SEM) and histochemistry to grow in multiple layers as a heterogenous cell population with different morphologies, contrasting 2D cultured mono-layered cells with a morphologically homogenous cell population. Gene expression analysis demonstrated that 3D TEMPO-CNF scaffolds induced elevation of the stemness marker CD44 and the migration markers VIM and SNAI1 in MCF7 cells relative to 2D control. T47D cells confirmed the increased level of the stemness marker CD44 and migration marker VIM which was further supported by increased capacity of holoclone formation for 3D cultured cells. Therefore, TEMPO-CNF was shown to represent a promising material for 3D cell culture model systems for cancer cell applications such as drug screening. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 37. |
- Stangegaard, M., et al.
(författare)
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A biocompatible micro cell culture chamber (microCCC) for the culturing and on-line monitoring of eukaryote cells
- 2006
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Ingår i: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 6:8, s. 1045-1051
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that a polymeric (PMMA) chip with medium perfusion and integrated heat regulation provides sufficiently precise heat regulation, pH-control and medium exchange to support cell growth for weeks. However, it was unclear how closely the cells cultured in the chip resembled cells cultured in the culture flask. In the current study, gene expression profiles of cells cultured in the chip were compared with gene expression profiles of cells cultured in culture flasks. The results showed that there were only two genes that were differently expressed in cells grown in the cell culture chip compared to cell culture flasks. The cell culture chip could without further modification support cell growth of two other cell lines. Light coming from the microscope lamp during optical recordings of the cells was the only external factor identified, that could have a negative effect on cell survival. Low grade light exposure was however compatible with optical recordings as well as cell viability. These results strongly indicate that a cell culture chip could be constructed that allowed for on-line optical recording of cellular events without affecting the cell culturing condition compared to cell cultured in culture flasks incubated in a dark and CO 2 conditioned incubator. © The Royal Society of Chemistry 2006.
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| 38. |
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| 39. |
- Sul, Young-Taeg, 1960, et al.
(författare)
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Characteristics of the surface oxides on turned and electrochemically oxidized pure titanium implants up to dielectric breakdown: the oxide thickness, micropore configurations, surface roughness, crystal structure and chemical composition.
- 2002
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Ingår i: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:2, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Titanium implants have been used widely and successfully for various types of bone-anchored reconstructions. It is believed that properties of oxide films covering titanium implant surfaces are of crucial importance for a successful osseointegration, in particular at compromized bone sites. The aim of the present study is to investigate the surface properties of anodic oxides formed on commercially pure (c.p.) titanium screw implants as well as to study 'native' oxides on turned c.p. titanium implants. Anodic oxides were prepared by galvanostatic mode in CH3COOH up to the high forming voltage of dielectric breakdown and spark formation. The oxide thicknesses, measured with Auger electron spectroscopy (AES), were in the range of about 200-1000 nm. Barrier and porous structures dominated the surface morphology of the anodic film. Quantitative morphometric analyses of the micropore structures were performed using an image analysis system on scanning electron microscopy (SEM) negatives. The pore sizes were
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| 40. |
- Svanström, Andreas, et al.
(författare)
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Optimized alginate-based 3D printed scaffolds as a model of patient derived breast cancer microenvironments in drug discovery
- 2021
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Ingår i: Biomedical Materials (Bristol). - : IOP Publishing Ltd. - 1748-6041 .- 1748-605X. ; 16:4
-
Tidskriftsartikel (refereegranskat)abstract
- The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting of a 3D grid containing periostin and hydroxyapatite. Breast cancer cell lines (MCF7 and MDA-MB-231) produced similar phenotypes and gene expression levels of cancer stem cell, epithelial-mesenchymal transition, differentiation and proliferation markers when cultured on 3DPS and PDS, contrasting conventional 2D cultures. Importantly, cells cultured on 3DPS and PDS showed scaffold-specific responses to cytotoxic drugs (doxorubicin and 5-fluorouracil) that were different from 2D cultured cells. In conclusion, the data presented support the use of a tunable alginate-based 3DPS as a tumor model in breast cancer drug discovery. © 2021 The Author(s). Published by IOP Publishing Ltd.
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| 41. |
- Svensson, Sara, 1981, et al.
(författare)
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A novel soft tissue model for biomaterial-associated infection and inflammation - Bacteriological, morphological and molecular observations
- 2015
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 41, s. 106-121
-
Tidskriftsartikel (refereegranskat)abstract
- Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.
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| 42. |
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| 43. |
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| 44. |
- Thorarinsdottir, Hulda R, et al.
(författare)
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Biofilm formation on three different endotracheal tubes : a prospective clinical trial
- 2020
-
Ingår i: Critical Care. - : NLM (Medline). - 1364-8535 .- 1466-609X. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. METHODS: We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. RESULTS: High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14-15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06-0.59], p = 0.005, and OR 0.34 [95% CI 0.13-0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17-1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. CONCLUSION: High-grade biofilm formation on ETTs was associated with development of VAP. Compared to the uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation. Further research on methods to prevent, monitor, and manage biofilm occurrence is needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02284438 . Retrospectively registered on 21 October 2014.
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| 45. |
- Tymchenko, Nina, 1977, et al.
(författare)
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A novel cell force sensor for quantification of traction during cell spreading and contact guidance
- 2007
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Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 93, s. 335-345
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we present a ridged, microfabricated, force sensor that can be used to investigate mechanical interactions between cells exhibiting contact guidance and the underlying cell culture substrate, and a proof-of-function evaluation of the force sensor performance. The substrates contain arrays of vertical pillars between solid ridges that were microfabricated in silicon wafers using photolithography and deep reactive ion etching. The spring constant of the pillars was measured by atomic force microscopy. For time-lapse experiments, cells were seeded on the pillared substrates and cultured in an on-stage incubator on a microscope equipped with re. flected differential interference contrast optics. Endothelial cells (ECs) and. broblasts were observed during attachment, spreading, and migration. Custom image analysis software was developed to resolve cell borders, cell alignment to the pillars and migration, displacements of individual pillars, and to quantify cell traction forces. Contact guidance classifi. cation was based on cell alignment and movement angles with respect to microfabricated ridges, as well as cell elongation. In initial investigations made with the ridged cell force sensor, we have observed contact guidance in ECs but not in. broblast cells. A difference in maximal amplitude of mechanical forces was observed between a contact-guided and non-contact-guided, but mobile, EC. However, further experiments are required to determine the statistical significance of this observation. By chance, we observed another feature of cell behavior, namely a reversion of cell force direction. The direction of forces measured under rounded. broblast cells changed from outwards during early cell attachment to inwards during further observation of the spreading phase. The range of forces measured under. broblasts (up to 138 nN) was greater than that measured in EC (up to 57 nN), showing that the rigid silicon sensor is capable of resolving a large range of forces, and hence detection of differences in traction forces between cell types. These observations indicate proof-of-function of the ridged cell force sensor to induce contact guidance, and that the pillared cell force sensor constructed in rigid silicon has the necessary sensitivity to detect differences in traction force vectors between different cell phenotypes and morphologies.
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| 46. |
- Wells, James, et al.
(författare)
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Standardisation of magnetic nanoparticles in liquid suspension
- 2017
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Ingår i: Journal of Physics D: Applied Physics. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 50:383003, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation,spanning a large number of industry sectors from imaging and actuation based applicationsin biomedicine and biotechnology, through large-scale environmental remediation uses suchas water purification, to engineering-based applications such as position-controlled lubricantsand soaps. Continuous advances in their manufacture have produced an ever-growing rangeof products, each with their own unique properties. At the same time, the characterisation ofmagnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpretthe measurement data. In many cases, the stringent requirements of the end-user technologiesdictate that magnetic nanoparticle products should be clearly defined, well characterised,consistent and safe; or to put it another way—standardised. The aims of this document areto outline the concepts and terminology necessary for discussion of magnetic nanoparticles,to examine the current state-of-the-art in characterisation methods necessary for the mostprominent applications of magnetic nanoparticle suspensions, to suggest a possible structurefor the future development of standardisation within the field, and to identify areas and topicswhich deserve to be the focus of future work items. We discuss potential roadmaps for thefuture standardisation of this developing industry, and the likely challenges to be encounteredalong the way.
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| 47. |
- Wetterskog, Erik, et al.
(författare)
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Size and property bimodality in magnetic nanoparticle dispersions : single domain particles vs. strongly coupled nanoclusters
- 2017
-
Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 9:12, s. 4227-4235
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Tidskriftsartikel (refereegranskat)abstract
- The widespread use of magnetic nanoparticles in the biotechnical sector puts new demands on fast and quantitative characterization techniques for nanoparticle dispersions. In this work, we report the use of asymmetric flow field-flow fractionation (AF4) and ferromagnetic resonance (FMR) to study the properties of a commercial magnetic nanoparticle dispersion. We demonstrate the effectiveness of both techniques when subjected to a dispersion with a bimodal size/magnetic property distribution: i.e., a small superparamagnetic fraction, and a larger blocked fraction of strongly coupled colloidal nanoclusters. We show that the oriented attachment of primary nanocrystals into colloidal nanoclusters drastically alters their static, dynamic, and magnetic resonance properties. Finally, we show how the FMR spectra are influenced by dynamical effects; agglomeration of the superparamagnetic fraction leads to reversible line-broadening; rotational alignment of the suspended nanoclusters results in shape-dependent resonance shifts. The AF4 and FMR measurements described herein are fast and simple, and therefore suitable for quality control procedures in commercial production of magnetic nanoparticles.
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| 48. |
- Österberg, Klas, 1966, et al.
(författare)
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Personalized tissue-engineered veins - long term safety, functionality and cellular transcriptome analysis in large animals
- 2023
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Ingår i: Biomaterials Science. - : NLM (Medline). - 2047-4830 .- 2047-4849. ; 11:11, s. 3860-3877
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Tidskriftsartikel (refereegranskat)abstract
- Tissue engineering is a promising methodology to produce advanced therapy medicinal products (ATMPs). We have developed personalized tissue engineered veins (P-TEV) as an alternative to autologous or synthetic vascular grafts utilized in reconstructive vein surgery. Our hypothesis is that individualization through reconditioning of a decellularized allogenic graft with autologous blood will prime the tissue for efficient recellularization, protect the graft from thrombosis, and decrease the risk of rejection. In this study, P-TEVs were transplanted to vena cava in pig, and the analysis of three veins after six months, six veins after 12 months and one vein after 14 months showed that all P-TEVs were fully patent, and the tissue was well recellularized and revascularized. To confirm that the ATMP product had the expected characteristics one year after transplantation, gene expression profiling of cells from P-TEV and native vena cava were analyzed and compared by qPCR and sequencing. The qPCR and bioinformatics analysis confirmed that the cells from the P-TEV were highly similar to the native cells, and we therefore conclude that P-TEV is functional and safe in large animals and have high potential for use as a clinical transplant graft.
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