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  • 1.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Carter, Sarah-Sophia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Bone Cement Embedded in a Microfluidic Device2018Conference paper (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) have a great potential in the treatment of bone disorders due to their excellent biocompatibility. Although CPCs are promising when implanted in vivo, there is poor correlation between in vitro and in vivo studies. This could be because most conventional in vitro systems lack a 3D architecture, or dynamic conditions (i.e. a continuous refreshment stream). The aim of this work is to embed CPCs into a microfluidic system and evaluate ion and protein exchange at different flow rates.

  • 2.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Evaluation of Ionic Interactions of Bone Cement-on-Chip2019Conference paper (Other academic)
    Abstract [en]

    INTRODUCTION: Biomaterials are synthetic materials that can be incorporated into the body to replace an impaired physiological function. Apatite calcium phosphate cements (CPCs), used for bone regeneration, give calcium-deficient hydroxyapatite (CDHA) as an end-product after a dissolution-precipitation reaction during fabrication. CDHA has a tendency to uptake calcium and release phosphate into cell culture medium. Potentially, this leads to depletion of calcium ions in solution, which can be detrimental to cell survival. The aim of this work is to embed CDHA in a microfluidic system and evaluate ion exchange at different flow rates.

    METHODS: CPC paste was cast into a 0.8mm pocket within a Polydimethylsiloxane (PDMS, cured at 60°C for 2h) mould. CPCs were set in 0.9% w/v NaCl at 37°C for 10 days resulting in CDHA. The PDMS containing the CDHA was then bonded to glass, leaving a 0.5mm channel gap. Minimum Essential Media (MEM, 1ml) was pumped through the channel at low (2µl/min), medium (8µl/min) and high (14µl/min) flow rates. A CDHA disc (ø=15mm, h=2mm) was immersed in MEM (1ml) at static conditions (0µl/min) for 24h. Stock Media was taken as control. Calcium and phosphorus concentrations were analysed using Inductively Coupled Plasma Optical Emission Spectroscopy.

    RESULTS & CONCLUSIONS: CDHA was successfully embedded in a microfluidic chip (Fig. 1A). Observed [Ca] and [P] levels were closer to levels in stock MEM at higher flow rates (Fig. 1B). We anticipate that osteoblast viability will improve when grown under flow, as opposed to static conditions, due to continuous replenishment of cell medium.

  • 3.
    Blasi Romero, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Barbe, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties2019Conference paper (Other academic)
  • 4.
    Canal, Cristina
    et al.
    Technical University of Catalonia.
    Pastorino, David
    Technical University of Catalonia.
    Mestres, Gemma
    Technical University of Catalonia.
    Schuler, Philipp
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Relevance of microstructure for the early antibiotic release of fresh and pre-set calcium phosphate cements2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 9, p. 8403-8412Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction.The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of a-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.

  • 5.
    Carlsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Treerattrakoon, Kiatnida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lopez, Alejandro
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vitro and in vivo response to low-modulus PMMA-based bone cement2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 594284Article in journal (Refereed)
    Abstract [en]

    The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.

  • 6.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Atif, Abdul
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Lanekoff, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tailoring the biocompatibility of the elastomer PDMS for on-chip applications2018Conference paper (Refereed)
  • 7.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Atif, Abdul Raouf M.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Lanekoff, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Improving the biocompatibility of PDMS by improving its curing time and temperature2018Conference paper (Other academic)
  • 8.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Cruz, Javier
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Towards the development of a microfluidic tool to assess the biological properties of biomaterials for bone regeneration2018Conference paper (Refereed)
  • 9.
    Carter, Sarah-Sophia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Moreira, Milena
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration2019Conference paper (Other academic)
    Abstract [en]

    Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration

     

    Sarah-Sophia D. Carter1, Hugo Nguyen2, Milena Moreira1, Maria Tenje1, and Gemma Mestres1

    1Department of Engineering Sciences, Science for Life Laboratory, Uppsala University, Sweden

    2Department of Engineering Sciences, Uppsala University, Sweden

     

    Introduction

    Before entering the clinic, biomaterials need to be thoroughly evaluated, which requires accurate in vitro models. In this work, we have developed a microfluidic device that could be used to assess the biological properties of biomaterials, in a more in vivo-like environment than what is currently possible.

     

    Methods

    Our device consists of a polydimethylsiloxane (PDMS, Sylgard 184) microfluidic channel (l= 6 mm, w= 2 mm, h= 200 µm) and a titanium disc (Ti6Al4V, at bottom), held together by an additively manufactured fixture (Fig. 1A). PDMS was cured overnight at 65°C on a silicon wafer master. Once the microchannel and titanium disc were positioned, MC3T3-E1 pre-osteoblast-like cells were seeded (50,000 cells/cm2). After 5 hours incubation under standard culture conditions, flow was started (2 μl/min). As a control, MC3T3-E1 cells were seeded onto plain titanium discs off-chip. Cell viability and morphology were assessed after 20 hours by calcein-AM/propidium iodide (PI), staining live and dead cells respectively.

     

    Results and discussion

    Figure 1B and 1C show calcein-AM/PI stained MC3T3-E1 cells cultured on-chip and figure 1D shows the control, MC3T3-E1 cells cultured off-chip. The potential to culture cells in our chip was confirmed by the presence of a majority of viable cells (green) with a similar morphology as the control sample. The reason for the increased amount of dead cells (red) on-chip compared to the control needs to be further examined, which requires longer-term experiments.

    Conclusion

    We have set the first steps towards a microfluidic tool for the assessment of biological properties of biomaterials.

  • 10.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lan, Weihua
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Cytotoxicity of modified glass ionomer cement on odontoblast cells2016In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 27, no 7, article id 116Article in journal (Refereed)
    Abstract [en]

    Recently a modified glass ionomer cement (GIC) with enhanced bioactivity due to the incorporation of wollastonite or mineral trioxide aggregate (MTA) has been reported. The aim of this study was to evaluate the cytotoxic effect of the modified GIC on odontoblast-like cells. The cytotoxicity of a conventional GIC, wollastonite modified GIC (W-mGIC), MTA modified GIC (M-mGIC) and MTA cement has been evaluated using cement extracts, a culture media modified by the cement. Ion concentration and pH of each material in the culture media were measured and correlated to the results of the cytotoxicity study. Among the four groups, conventional GIC showed the most cytotoxicity effect, followed by W-mGIC and M-mGIC. MTA showed the least toxic effect. GIC showed the lowest pH (6.36) while MTA showed the highest (8.62). In terms of ion concentration, MTA showed the largest Ca2+ concentration (467.3 mg/L) while GIC showed the highest concentration of Si4+ (19.9 mg/L), Al3+ (7.2 mg/L) and Sr2+ (100.3 mg/L). Concentration of F- was under the detection limit (0.02 mg/L) for all samples. However the concentrations of these ions are considered too low to be toxic. Our study showed that the cytotoxicity of conventional GIC can be moderated by incorporating calcium silicate based ceramics. The modified GIC might be promising as novel dental restorative cements.

  • 11.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lan, Weihua
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vitro cytotoxicity of dental cements on odontoblast cells2016Conference paper (Refereed)
  • 12.
    D’Elía, Noelia L.
    et al.
    Universidad Nacional del Sur, Argentina.
    Rial Silva, Ramon
    Universidad Santiago de Compostela, Spain.
    Sartuqui, Javier
    Universidad Nacional del Sur, Argentina.
    Ercoli, Daniel
    Planta Piloto de Ingeniería Química – PLAPIQUI (UNS-CONICET), Argentina.
    Ruso, Juan
    Universidad Santiago de Compostela, Spain.
    Messina, Paula
    Universidad Nacional del Sur, Argentina.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alginate - hydroxyapatite composites for guided bone regeneration: rheology and tensile strength2019Conference paper (Other academic)
  • 13.
    Diez-Escudero, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Liu, Yuling
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lançon, Victorine
    KTH Royal Institute of Technology, Stockholm.
    Widhe, Mona
    KTH Royal Institute of Technology, Stockholm.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Hedhammar, My
    KTH Royal Institute of Technology, Stockholm.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Recombinant silk with calcium phosphates as macroporous bone scaffolds2019Conference paper (Refereed)
  • 14. Espanol, Montse
    et al.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Luxbacher, Thomas
    Ginebra, Maria-Pau
    The Role of Porosity on the Z-Potential of Calcium Phosphate Cements2014Conference paper (Refereed)
  • 15. Espanol, Montserrat
    et al.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Luxbacher, Thomas
    Dory, Jean-Baptiste
    Ginebra, Maria-Pau
    Impact of Porosity and Electrolyte Composition on the Surface Charge of Hydroxyapatite Biomaterials2016In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 8, no 1, p. 908-917Article in journal (Refereed)
    Abstract [en]

    The success or failure of a material when implanted in the body is greatly determined by the surface properties of the material and the host tissue reactions. The very first event that takes place after implantation is the interaction of soluble ions, molecules and proteins from the biological environment with the material surface leading to the formation of an adsorbed protein layer that will later influence cell attachment. In this context, the particular topography and surface charge of a material become critical as they influence the nature of the proteins that will adsorb. However, very limited information is available on the surface charge of porous substrates. Only until very recently was the determination of the zeta potential on porous membranes accurately determined. The goal of this work was to implement the previous findings for the determination of the zeta potential of a series of porous hydroxyapatite (HA) substrates and to assess how porosity affects the measurements. In addition, studies using various electrolytes were also performed to prove how the specific affinity of certain ions for HA can further impact surface charge. The results showed that all materials exhibited very similar external surface charge (approximately −23 mV), consistent with their almost identical topographies. However, the presence of interconnected pores underneath the sample surface resulted in an additional internal zeta potential that varied with the porosity content. Measurements with different electrolytes confirmed the selectivity of divalent ions for HA underlying the importance of testing biomaterials using relevant electrolytes.

  • 16.
    Gallinetti, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Universitat Politècnica de Cataluny; Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain .
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Canal, Cristina
    Universitat Politècnica de Catalunya; Barcelona Research Center in Multiscale Science and Engineering.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Universitat Politècnica de Catalunya; Barcelona Research Center in Multiscale Science and Engineering.
    A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement2017In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 75, p. 495-503Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are extensively used as synthetic bone grafts, but their poor toughness limits their use to non-load-bearing applications. Reinforcement through introduction of fibers and yarns has been evaluated in various studies but always resulted in a decrease in elastic modulus or bending strength when compared to the CPC matrix. The aim of the present work was to improve the interfacial adhesion between fibers and matrix to obtain tougher biocompatible fiber-reinforced calcium phosphate cements (FRCPCs). This was done by adding a polymer solution to the matrix, with chemical affinity to the reinforcing chitosan fibers, namely trimethyl chitosan (TMC). The improved wettability and chemical affinity of the chitosan fibers with the TMC in the liquid phase led to an enhancement of the interfacial adhesion. This resulted in an increase of the work of fracture (several hundred-fold increase), while the elastic modulus and bending strength were maintained similar to the materials without additives. Additionally the TMC-modified CPCs showed suitable biocompatibility with an osteoblastic cell line.

  • 17. Gallinetti, Sara
    et al.
    Mestres, Gemma
    Persson, Cecilia
    Canal, Cristina
    Ginebra, Maria-Pau
    A new approach for fibre reinforced calcium phosphate cements2014Conference paper (Refereed)
  • 18.
    Ginebra, Maria-Pau
    et al.
    Technical University of Catalonia.
    Montserrat, Espanol
    Technical University of Catalonia.
    Montufar, Edgar Benjamin
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering.
    Perez, Roman A
    Mestres, Gemma
    Technical University of Catalonia.
    New processing approaches in calcium phosphate cements and their applicationsin regenerative medicine2010In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 6, no 8, p. 2863-2873Article, review/survey (Refereed)
    Abstract [en]

    The key feature of calcium phosphate cements (CPCs) lies in the setting reaction triggered by mixing oneor more solid calcium phosphate salts with an aqueous solution. Upon mixture, the reaction takes placethrough a dissolution–precipitation process which is macroscopically observed by a gradual hardening ofthe cement paste. The precipitation of hydroxyapatite nanocrystals at body or room temperature, and the fact that those materials can be used as self-setting pastes, have for many years been the most attractivefeatures of CPCs. However, the need to develop materials able to sustain bone tissue ingrowth and be capable of delivering drugs and bioactive molecules, together with the continuous requirement from surgeons to develop more easily handling cements, has pushed the development of new processing routes that can accommodate all these requirements, taking advantage of the possibility of manipulating the self-setting CPC paste. It is the goal of this paper to provide a brief overview of the new processing developments in the area of CPCs and to identify the most significant achievements.

  • 19.
    Jocic, Simonne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cross-linked gelatin/agarose conjugate as a thermostable and biocompatible microfluidic material2016Conference paper (Refereed)
  • 20.
    Jocic, Simonne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab. Lund University, Dept. Biomedical Engineering, Lund 221 00, Sweden.
    Fabrication of user-friendly and biomimetic 1,1′-carbonyldiimidazole cross-linked gelatin/agar microfluidic devices2017In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 76, p. 1175-1180Article in journal (Refereed)
    Abstract [en]

    We have developed a straightforward technique for fabricating user-friendly and biomimetic microfluidic devices out of a gelatin/agar gel cross-linked with 1,1′-carbonyldiimidazole. The fabrication procedure requires only inexpensive starting materials such as glass capillaries and wires to mold 3D cylindrical channels into the gel with the possibility of achieving channel diameters of 375 μm and 1000 μm. We demonstrate that the channel absent of gel injury can retain fluid within its dimensions for at least 7 h. We also show that the device material does not autofluoresce nor provide hindrances with fluorescent imaging. A discussion of the chemical linkage identities of cross-linked gelatin/agar is included via ATR-FTIR studies. Crosslinking of the gelatin/agar is further confirmed by the lack of a gel to sol transition at physiological temperature as assessed by DSC measurements. SEM micrographs that demonstrate the 100 nm mean pore width of the cross-linked gelatin/agar are provided. This device is considered biomimetic because it represents components present in the natural extracellular matrix such as collagen and proteoglycans in the form of cross-linked gelatin/agar.

  • 21. Lee, Bryan
    et al.
    Samantha, Ho
    Gemma, Mestres
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Marjam, Karlsson Ott
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Philip, Koshy
    Kathryn, Grandfield
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Dual-Topography Electric Discharge Machining of Titanium to Improve Biocompatibility2016In: Surface and Coatings Technology, ISSN 0257-8972, Vol. 296, p. 149-156Article in journal (Refereed)
    Abstract [en]

    Surface modifications of titanium are widespread in an effort to improve the osseointegration capabilities of the metal for orthopaedic and dental applications. Here, electrical discharge machining (EDM) was used to create modified, notably, dual-topography surfaces on titanium. By swapping conventional copper electrodes for a titanium electrode and water dielectric, modified surfaces free of trace element contaminants were produced. Three surfaces were produced by varying the peak currents at 10 A, 29 A and a uniquely hierarchical multi current combination of 29 A followed by 2.4 A. The physicochemical properties of these surfaces were analyzed by scanning electron microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and Auger Spectroscopy. These revealed the topography of the modified surfaces and a titanium oxide layer that was markedly thicker on the EDM samples compared to controls. In vitro cell testing was carried out with osteoblast-like MC3T3-E1 cells. Cell differentiation was increased in all EDM modified surfaces compared to controls and early differentiation was promoted on the dual-topography surface. The present study suggests the promise of dual-topography surfaces created using EDM for implant applications.

  • 22.
    Lopez, Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ferguson, SJ
    Helgason, B
    Persson, Cecilia
    Mechanical and in vitro evaluation of low-modulus bone cement - Osteopal®V modified with linoleic acid2012Conference paper (Refereed)
  • 23. Lu, Xi
    et al.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Effati, Pedram
    Pal Singh, V
    Poon, JF
    Engman, Lars
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Novel selenium- and tellurium-based antioxidants as modulators of inflammatory response2015Conference paper (Refereed)
  • 24.
    Lu, Xi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Effati, Pedram
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Singh, VP
    Poon, J
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Novel selenium- and tellurium-based antioxidants as modulators of inflammatory response2015In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 29, no Supp.1, p. 33-33Article in journal (Refereed)
  • 25.
    Lu, Xi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Singh, Vijay Pal
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Effati, Pedram
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Poon, Jia-Fei
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Engman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Marjam, Karlsson Ott
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity2017In: Antioxidants, E-ISSN 2076-3921, Vol. 6, no 13, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2 -induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

  • 26. Luxbacher, Thomas
    et al.
    Espanol, Montse
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    The effect of porosity on the zeta potential of calcium phosphate cements2014In: BioNanoMaterials, ISSN 2193-066X, Vol. 15, no Supp.1, p. S46-Article in journal (Other academic)
  • 27. Luxbacher, Thomas
    et al.
    Espanol, Montse
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Ginebra, Maria-Pau
    The effect of porosity on the zeta potential of calcium phosphate cements2014Conference paper (Refereed)
  • 28.
    López, Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ferguson, Stephen J
    Swiss Federal Institute of Technology.
    Helgason, Benedikt
    Swiss Federal Institute of Technology.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mechanical and in vitro evaluation of low-modulus bone cement - Osteopal®V modified with linoleic acid2013In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262Article in journal (Refereed)
  • 29.
    López, Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ferguson, Stephen J.
    ETH Zurich.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Helgason, Benedikt
    ETH Zurich.
    Compressive mechanical properties and cytocompatibility of bone-compliant, linoleic acid-modified bone cement in a bovine model2014In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 32, p. 245-256Article in journal (Refereed)
    Abstract [en]

    Adjacent vertebral fractures are a common complication experienced by osteoporosis patients shortly after vertebroplasty. Whether these fractures are due to the bone cement properties, the cement filling characteristics or to the natural course of the disease is still unclear. However, some data suggests that such fractures might occur because of an imbalance in the load distribution due to a mismatch between the elastic modulus (E) of the bone-cement composite, and that of the vertebral cancellous bone. In this study, the properties of bone-compliant linoleic acid-modified bone cements were assessed using a bovine vertebroplasty model. Two groups of specimens (cement-only and bone-cement composites), and four subgroups comprising bone cements with elastic moduli in the range of 870-3500 MPa were tested to failure in uniaxial compression. In addition, monomer release as well as time and concentration-dependent cytocompatibility was assessed through the cement extracts using a Saos-2 cell model. Composites augmented with bone-compliant cements exhibited a reduction in E despite their relatively high bone volume fraction (BVF). Moreover, a significant positive correlation between the BVF and the E for the composites augmented with 870 MPa modulus cements was found. This was attributed to the increased relative contribution of the bone to the mechanical properties of the composites with a decrease in E of the bone cement. The use of linoleic acid reduced monomer conversion resulting in six times more monomer released after 24 h. However, the cytocompatibility of the bone-compliant cements was comparable to that of the unmodified cements after the extracts were diluted four times. This study represents an important step towards introducing viable bone-compliant bone cements into vertebroplasty practice.

  • 30. Manso, S
    et al.
    Mestres, G
    Ginebra, MP
    de Belie, N
    Segura, I
    Aguado, A
    Development of a low pH cementitious material to enlarge bioreceptivity2014In: Construction and Building Materials, Vol. 54, p. 485-495Article in journal (Refereed)
  • 31. Mas-Moruno, Carles
    et al.
    Espanol, Montserrat
    Montufar, Edgar-Benjamin
    Mestres, Gemma
    Aparicio, Conrado
    Gil, Francisco-Javier
    Ginebra, Maria-Pau
    Bioactive Ceramic and Metallic Surfaces for Bone Engineering (Chapter 12)2013In: Biomaterials Surface Science / [ed] Taubert A, Mano JF, Rodríguez-Cabello JC, Wiley-VCH , 2013Chapter in book (Other academic)
  • 32.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Abdolhosseini, M.
    Bowles, W.
    Huang, S. -H.
    Aparicio, C.
    Gorr, S.-U.
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Antimicrobial properties and dentin bonding strength of magnesium phosphate cements2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 9, p. 8384-8393Article in journal (Refereed)
    Abstract [en]

    The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH4H2PO4, NaH2PO4 or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH4PO46H2O) when NH4H2PO4 was used or an amorphous magnesium sodium phosphate when NaH2PO4 was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners.

  • 33. Mestres, Gemma
    et al.
    Aguilera, Fatima Sanchez
    Manzanares, Norbert
    Sauro, Salvatore
    Osorio, Raquel
    Toledano, Manuel
    Ginebra, Maria-Pau
    Novel magnesium phosphate cements for endodontic applications with improved long-term sealing ability2011In: International Endodontic Journal, Vol. 47, p. 127-139Article in journal (Refereed)
  • 34. Mestres, Gemma
    et al.
    Castano, Oscar
    Navarro, Melba
    Almirall, Amasel
    Ginebra, Maria-Pau
    Planell, Josep-Anton
    Micro and nanostructure evolution study of novel injectable calcium phosphate cements prepared by ceramic and sol-gel processes2007In: Tissue Engineering, Vol. 13, no 7, p. 1726-Article in journal (Refereed)
  • 35.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Espanol, Montse
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Immune responses to topographically different calcium phosphate cements2013In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 26, no Supp.2, p. 19-19Article in journal (Other academic)
  • 36. Mestres, Gemma
    et al.
    Espanol, Montse
    Persson, Cecilia
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Impoverishment of media by bioactive hydroxyapatite hinders cell proliferation2015Conference paper (Refereed)
  • 37.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Espanol, Montse
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Impoverishment of media by bioactive hydroxyapatite hinders cell proliferation2015In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 29, no Suppl.1, p. 36-36Article in journal (Refereed)
  • 38.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Espanol, Montse
    Persson, Cecilia
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Inflammatory response to calcium phosphate cements with patterned surfaces2013Conference paper (Refereed)
  • 39. Mestres, Gemma
    et al.
    Espanol, Montserrat
    Persson, Cecilia
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Inflammatory Response to Calcium Phosphate Cements with Patterned Surfaces2013Conference paper (Refereed)
  • 40.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Espanol, Montserrat
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Inflammatory response to nano- and microstructured hydroxyapatite2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0120381Article in journal (Refereed)
    Abstract [en]

    The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal mor- phologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the ef- fect of supplementing the extracts with calcium ions and/or proteins was investigated. Mac- rophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate’s microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate- like crystals substrates compared to the almost non-existent release on needle-like sub- strates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials. 

  • 41.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Espanol, Montserrat
    Department of Engineering Sciences and Metallurgy, Technical University of Catalonia, Diagonal 647, 08028 Barcelona, Spain.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Department of Biomedical Engineering, Lund University, Box 118, 221 00 Lund, Sweden.
    Ott, Marjam
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of Biocompatibility and Release of Reactive Oxygen Species of Aluminum Oxide-Coated Materials2016In: ACS Omega, ISSN 2470-1343, Vol. 1, no 4, p. 706-713Article in journal (Refereed)
    Abstract [en]

    Surface properties of biomaterials can strongly influence biomaterial−host interactions. For this reason, coating processes open a wide range of possibilities to modulate the fate of a biomaterial in the body. This study evaluates the effect of a coating material intended for drug delivery capsules on biocompatibility and the release of reactive oxygen species (ROS), that is, respiratory burst in macrophages that indicates acute inflammation. In parallel with a new approach to develop drug-delivery capsules by directly coating solid-state drug particles, in this study, glass slides and silicon nanoparticles (NPs) were coated with aluminum oxide (Al2O3) using atomic layer deposition. Different sizes of NPs (20 and 310 nm) were suspended at different concentrations (10, 100, and 1000 μg/mL) and were evaluated. The homogeneous coating of slides was proved using X-ray photoelectron spectroscopy, and the coating on NP was observed using transmission electron microscopy. Human dermal fibroblasts and human osteoblasts were able to proliferate on the coated slides and in the presence of a suspension of coated NPs (20 and 310 nm) at a low concentration (10 μg/mL). The macrophages released ROS only when in contact with NPs at a concentration of 1000 μg/mL, where the 20 nm NPs caused a higher release of ROS than the 310 nm NPs. This study shows that Al2O3 coatings do not affect the cells negatively and that the cell viability was compromised only when in contact with a high concentration (1000 μg/mL) of smaller (20 nm) NPs. 

  • 42.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fernandez-Yague, Marc Antoni
    Technical University of Catalonia (UPC).
    Pastorino, David
    Technical University of Catalonia.
    Montufar, Edgar Benjamin
    Brno University of Technology.
    Canal, Cristina
    Technical University of Catalonia.
    Manzanares-Céspedes, Maria-Cristina
    University of Barcelona.
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    In vivo efficiency of antimicrobial inorganic bone grafts in osteomyelitis Treatments2019In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, p. 84-95Article in journal (Refereed)
    Abstract [en]

    The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 μm vs. macroporosity, i.e. >5 μm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.

    The full text will be freely available from 2020-11-28 11:07
  • 43. Mestres, Gemma
    et al.
    Ginebra, Maria-Pau
    Magnesium phosphate cements for clinical applications: Suitable for endodontic applications2014Book (Other academic)
  • 44.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Novel magnesium phosphate cements with high early strength and antibacterial properties2011In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, p. 1853-1861Article in journal (Refereed)
    Abstract [en]

    Magnesium phosphate cements (MPCs) have been extensively used as fast setting repair cements in civil engineering. They have properties that are also relevant to biomedical applications, such as fast setting, early strength acquisition and adhesive properties. However, there are some aspects that should be improved before they can be used in the human body, namely their highly exothermic setting reaction and the release of potentially harmful ammonia or ammonium ions. In this paper a new family of MPCs was explored as candidate biomaterials for hard tissue applications. The cements were prepared by mixing magnesium oxide (MgO) with either sodium dihydrogen phosphate (NaH2PO4) or ammonium dihydrogenphosphate (NH4H2PO4), or an equimolar mixture of both. The exothermia and setting kinetics of the new cement formulations were tailored to comply with clinical requirements by adjusting the granularity of the phosphate salt and by using sodium borate as a retardant. The ammonium-containing MPC resulted in struvite (MgNH4PO46H2O) as the major reaction product, whereas the MPC prepared with sodium dihydrogenphosphate resulted in an amorphous product. Unreacted magnesium oxide was found in all the formulations.The MPCs studied showed early compressive strengths substantially higher than that of apatitic calcium phosphate cements. The Na-containing MPCs were shown to have antibacterial activity against Streptococcus sanguinis, which was attributed to the alkaline pH developed during the setting reaction.

  • 45.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Kugiejko, Karol
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Effect of Setting Time on Drug Release from a Brushite Cement2014Conference paper (Refereed)
  • 46.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Kugiejko, Karol
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pastorino, David
    Unosson, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Tech Univ Catalonia UPC, Dept Mat Sci & Met, Biomat Biomech & Tissue Engn Grp, Barcelona 08028, Spain.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement2016In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 58, p. 88-96Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions.They can be applied by minimally invasive surgery and can also be used as drug delivery systems.Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest.However, previous studies have commonly evaluated the drug release using pre-set cements only.Therefore, the aim of this work was to determine if the time elapsed from cement preparation untilimmersion in the solution (3 min for fresh cements, and 1 h and 15 h for pre-set cements) had aninfluence on its physical properties, and correlating these to the drug release profile. Simvastatin wasselected as a model drug, while brushite cement was used as drug carrier. This study quantified howthe setting of a material reduces the accessibility of the release media to the material, thus preventingdrug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements toa sustained release for pre-set cements.

  • 47.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Le Van, Clemence
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Silicon-stabilized a-tricalcium phosphate and its use in a calcium phosphate cement: Characterization and cell response2012In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 8, no 3, p. 1169-1179Article in journal (Refereed)
    Abstract [en]

    a-Tricalcium phosphate (a-TCP) is widely used as a reactant in calcium phosphate cements. This work aims at doping a-TCP with silicon with a two-fold objective. On the one hand, to study the effect of Si addition on the stability and reactivity of this polymorph. On the other, to develop Si-doped cements and to evaluate the effect of Si on their in vitro cell response. For this purpose a calcium-deficient hydroxyapatite was sintered at 1250 C with different amounts of silicon oxide. The high temperature polymorpha-TCP was stabilized by the presence of silicon, which inhibited reversion of the b?a transformation, whereas in the Si-free sample a-TCP completely reverted to the b-polymorph. However, the b–a transformation temperature was not affected by the presence of Si. Si–a-TCP and its Si-free counterpart were used as reactants for a calcium phosphate cement. While Si–a-TCP showed faster hydrolysis to calcium deficient hydroxyapatite, upon complete reaction the crystalline phases, morphology and mechanical properties of both cements were similar. An in vitro cell culture study, in which osteoblast-like cells were exposed to the ions released by both materials, showed a delay in cell proliferation in both cases and stimulation of cell differentiation, more marked for the Si-containing cement. These results can be attributed to strong modification of the ionic concentrations in the culture medium by both materials. Ca depletion from the medium was observed for both cements, whereas continuous Si release was detected for the Si-containing cement.

  • 48.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Perez, Roman A.
    Universitat Internacional de Catalunya (Spain).
    d'Elía, Noelia
    Universidad Nacional del Sur (Argentina).
    Barbe, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Advantages of microfluidic systems for studying cell-biomaterial interactions: focus on bone regeneration applications2019In: Biomedical Physics & Engineering Express, ISSN 2057-1976, Vol. 5, no 3, article id 032001Article, review/survey (Refereed)
    Abstract [en]

    The poor correlation between in vitro and in vivo studies emphasises the lack of a reliable methodology for testing the biological properties of biomaterials in the bone tissue regeneration field. Moreover, the success of clinical trials is not guaranteed even with promising results in vivo. Therefore, there is a need for a more physiologically relevant in vitro model to test the biological properties of biomaterials. Microfluidics, which is a field concerning the manipulation and control of liquids at the submillimetre scale, can use channel geometry, cell confinement and fluid flow to recreate a physiological-like environment. This technology has already proven to be a powerful tool in studying the biological response of cells in defined environments, since chemical and mechanical inputs as well as cross-talk between cells can be finely controlled. Moving a step further in complexity, biomaterials can be integrated into microfluidic systems to evaluate biomaterial-cell interactions. The biomaterial- microfluidics combination has the potential to produce more physiologically relevant models to better screen the biological interactions established between biomaterials and cells. This review is divided into two main sections. First, several possible cell-based assays for bone regeneration studies in microfluidic systems are discussed. Second, and the ultimate goal of the review, is to discuss how the gap between in vitro and in vivo studies can be shortened by bridging the biomaterials and microfluidics fields.

    The full text will be freely available from 2020-04-06 08:51
  • 49. Mestres, Gemma
    et al.
    Santos, Carlos
    Engman, Lars
    Persson, Cecilia
    Karlsson Ott, Marjam
    Scavenging effect of Trolox released from brushite cements2014Conference paper (Refereed)
  • 50.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Santos, Carlos F
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Scavenging effect of Trolox released from brushite cements2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 11, p. 459-466Article in journal (Refereed)
    Abstract [en]

    In this study a brushite cement was doped with the chain-breaking antioxidant Trolox. The effect of the antioxidant on the physical properties of the cement was evaluated and the release of Trolox was monitored by UV spectroscopy. The ability of the Trolox set free to scavenge reactive oxygen species (ROS) released by macrophages was determined in vitro using a luminol-amplified chemiluminescence assay. Trolox did not modify the crystalline phases of the set cement, which mainly formed crystalline brushite after 7days in humid conditions. The setting time, compressive strength and morphology of the cement also remained unaltered after the addition of the antioxidant. Trolox was slowly released from the cement following a non-Fickian transport mechanism and nearly 64% of the total amount was released after 3days. Moreover, the capacity of Trolox to scavenge the ROS released by macrophages increased in a dose-dependent manner. Trolox-loaded cements are expected to reduce some of the first harmful effects of acute inflammation and can thus potentially protect the surrounding tissue during implantation of these as well as other materials used in conjunction.

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