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  • 1.
    Flys, Olena
    et al.
    RISE - Research Institutes of Sweden, Safety and Transport, Measurement Science and Technology. Halmstad University, Sweden.
    Jarlemark, Per
    RISE - Research Institutes of Sweden, Safety and Transport, Measurement Science and Technology.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Stenlund, Patrik
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Rosen, B. -G
    Halmstad University, Sweden.
    Applicability of characterization techniques on fine scale surfaces2018In: Surface Topography: Metrology and Properties, ISSN 2051-672X, Vol. 6, no 3, article id 034015Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Granskog, Viktor
    et al.
    KTH Royal Institute of Technology, Sweden.
    García-Gallego, Sandra
    KTH Royal Institute of Technology, Sweden.
    von Kieseritzky, Johanna
    Karolinska Institutet, Sweden.
    Rosendahl, Jennifer
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Stenlund, Patrik
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Zhang, Yuning
    KTH Royal Institute of Technology, Sweden.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Lyvén, Benny
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Arner, Marianne
    Karolinska Institutet, Sweden.
    Håkansson, Joakim
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Malkoch, Michael
    KTH Royal Institute of Technology, Sweden.
    High-Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair2018In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 28, no 26, article id 1800372Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Karazisis, Dimitrios
    et al.
    University of Gothenburg, Sweden.
    Ballo, Ahmed M.
    University of Gothenburg, Sweden; University of British Columbia, Canada.
    Petronis, Sarunas
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden.
    Agheli, Hossein
    University of Gothenburg, Sweden.
    Emanuelsson, Lena
    University of Gothenburg, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    Omar, Omar
    University of Gothenburg, Sweden.
    The role of well-defined nanotopography of titanium implants on osseointegration: Cellular and molecular events in vivo2016In: International Journal of Nanomedicine, ISSN 1176-9114, E-ISSN 1178-2013, Vol. 11, p. 1367-1382Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Karazisis, Dimitrios
    et al.
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials. BIOMATCELL, Sweden.
    Agheli, Hossein
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Emanuelsson, Lena
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Norlindh, Birgitta
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Johansson, Anna
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Rasmusson, Lars
    RISE - Research Institutes of Sweden, ICT, SICS.
    Thomsen, Peter
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Omar, Omar
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    The influence of controlled surface nanotopography on the early biological events of osseointegration.2017In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 53, p. 559-571Article in journal (Refereed)
    Abstract [en]

    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 30nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12h, 1d and 3d. 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 1d, and triggered the expression of osteocalcin (OC) at 3d. 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 3d. 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.

    STATEMENT OF SIGNIFICANCE: 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.

  • 5.
    Kuna, V K
    et al.
    University of Gothenburg, Sweden.
    Padma, A M
    University of Gothenburg, Sweden.
    Håkansson, Joakim
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Nygren, J
    TATAA Biocenter, Sweden.
    Sjöback, R
    TATAA Biocenter, Sweden.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Sumitran-Holgersson, S
    University of Gothenburg, Sweden.
    Significantly accelerated wound healing of full-thickness skin using a novel composite gel of porcine acellular dermal matrix and human peripheral blood cells2017In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, no 2, p. 293-307Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Sjövall, Peter
    et al.
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SP – Sveriges Tekniska Forskningsinstitut / Funktionella material (KMf).
    Lausmaa, Jukka
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SP – Sveriges Tekniska Forskningsinstitut / Funktionella material (KMf).
    Petronis, Sarunas
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro2014In: International Journal of Nanomedicine, ISSN 1176-9114, E-ISSN 1178-2013, Vol. 9, no 1, p. 2499-2515Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Svensson, Sara
    et al.
    University of Gothenburg, Sweden.
    Trobos, Margarita
    University of Gothenburg, Sweden.
    Hoffman, Maria
    University of Gothenburg, Sweden.
    Norlindh, Birgitta
    University of Gothenburg, Sweden.
    Petronis, Sarunas
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Lausmaa, Jukka
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SP – Sveriges Tekniska Forskningsinstitut / Funktionella material (KMf).
    Suska, Felicia
    University of Gothenburg, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    A novel soft tissue model for biomaterial-associated infection and inflammation - Bacteriological, morphological and molecular observations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 41, p. 106-121Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Wells, James
    et al.
    National Physical Laboratory, UK; Physikalisch-Technische Bundesanstalt, Germany.
    Kazakova, Olga
    National Physical Laboratory, UK.
    Posth, Oliver
    Physikalisch-Technische Bundesanstalt, Germany.
    Steinhoff, Uwe
    Physikalisch-Technische Bundesanstalt, Germany.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Bogart, Lara
    Healthcare Biomagnetics Laboratory, UK.
    Southern, Paul
    Healthcare Biomagnetics Laboratory, UK.
    Pankhurst, Quentin
    Healthcare Biomagnetics Laboratory, UK.
    Johansson, Christer
    RISE - Research Institutes of Sweden, ICT, Acreo.
    Standardisation of magnetic nanoparticles in liquid suspension2017In: Journal of Physics D: Applied Physics, Vol. 50, no 383003, p. 1-25Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Wetterskog, E
    et al.
    Uppsala University, Sweden.
    Castro, A
    SOLVE Research and Consultancy AB, Sweden.
    Zeng, L
    Chalmers University of Technology, Sweden .
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.
    Heinke, D
    nanoPET Pharma GmbH, Germany.
    Olsson, E
    Chalmers University of Technology, Sweden .
    Nilsson, L
    Lund University, Sweden; SOLVE Research and Consultancy AB, Sweden.
    Gehrke, N
    nanoPET Pharma GmbH, Germany.
    Svedlindh, P
    Uppsala University, Sweden.
    Size and property bimodality in magnetic nanoparticle dispersions: single domain particles vs. strongly coupled nanoclusters2017In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 9, no 12, p. 4227-4235Article in journal (Refereed)
    Abstract [en]

    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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