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  • 1.
    Aarstad, Olav
    et al.
    NTNU Norwegian University of Science and Technology, Norway.
    Heggset, Ellinor B
    RISE - Research Institutes of Sweden (2017-2019), Bioeconomy, PFI.
    Pedersen, Ina Sander
    NTNU Norwegian University of Science and Technology, Norway.
    Björnöy, Sindre H.
    NTNU Norwegian University of Science and Technology, Norway.
    Syverud, Kristin
    RISE - Research Institutes of Sweden (2017-2019), Bioeconomy, PFI.
    Strand, Berit L.
    NTNU Norwegian University of Science and Technology, Norway.
    Mechanical properties of composite hydrogels of alginate and cellulose nanofibrils2017In: Polymers, E-ISSN 2073-4360, Vol. 9, no 8, article id 378Article in journal (Refereed)
    Abstract [en]

    Alginate and cellulose nanofibrils (CNF) are attractive materials for tissue engineering and regenerative medicine. CNF gels are generally weaker and more brittle than alginate gels, while alginate gels are elastic and have high rupture strength. Alginate properties depend on their guluronan and mannuronan content and their sequence pattern and molecular weight. Likewise, CNF exists in various qualities with properties depending on, e.g., morphology and charge density. In this study combinations of three types of alginate with different composition and two types of CNF with different charge and degree of fibrillation have been studied. Assessments of the composite gels revealed that attractive properties like high rupture strength, high compressibility, high gel rigidity at small deformations (Young’s modulus), and low syneresis was obtained compared to the pure gels. The effects varied with relative amounts of CNF and alginate, alginate type, and CNF quality. The largest effects were obtained by combining oxidized CNF with the alginates. Hence, by combining the two biopolymers in composite gels, it is possible to tune the rupture strength, Young’s modulus, syneresis, as well as stability in physiological saline solution, which are all important properties for the use as scaffolds in tissue engineering.

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  • 2.
    Abbasi Aval, Negar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Utilizing Biopolymers in 3D Tumor Modeling and Tumor Diagnosis2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cancer represents a significant global public health challenge and ranks as the second mostcommon cause of death in the United States. The onset of cancer entails an initial phasewhere cells lose their polarity and disconnect from the normal basement membrane, allowingthem to form distinct three-dimensional (3D) configurations that interact with adjacent cellsand the surrounding microenvironment. Cells grown in 2D monolayers demonstrate differentgene expression patterns and different activation of signaling pathways compared to cellscultivated within the natural structure of tumor tissue of the same cell type. Multicellulartumor spheroids (MCTS) are extensively investigated as a well-studied model of organotypiccancer. These spheroids are formed by tumor cells, either alone or in combination with othercell types, and they can be created with or without the application of supportive scaffolds.The MCTSs are also considered promising models for preclinical assessments of chemosensitivity.However, the creation of these tumor spheroids presents challenges, as not alltumor cell lines can consistently form regular spheroids.Cellulose nanofibrils (CNF) have become essential as a sustainable and environmentallyfriendly material. For example, thin films, with inherent mechanical properties, and flexibility,offer versatility across various applications. Also known for its biocompatibility and non-toxicnature, native CNF is a natural option to use. Its fibrous structure closely mimics the collagenmatrix in human tissue, showing potential as an effective scaffold for 3D cell culture. In thisregard, an innovative Layer-by-Layer (LbL) coating technique using CNF-polyelectrolytebilayers was investigated to generate spheroids. This method constructs bilayers of CNFand polyelectrolytes and can coat various surfaces. In this thesis, the first focus was ondemonstrating the spheroid formation capability using low molecular weight polyelectrolytesin LbL assembly. Secondly, an investigation was conducted involving embedding of LbLgrownspheroids in a decellularized extracellular matrix (ECM) aiming to determine howECM, possessing suitable mechanical characteristics, could influence the cancer stem celltraits in spheroids. Thirdly, the thesis demonstrated the utilization of LbL for capturing andreleasing of circulating tumor cells. Lastly, the shift from using low molecular weightpolyelectrolytes in the LbL assembly to high molecular weight counterparts and analyzingthe differences in spheroid formation abilities to assess the underlying differences inmolecular weights of the polyelectrolytes was explored. All-in-all, employing the CNF-basedLbL surface coating strategy explored in the thesis has proven to be promising for thedevelopment of spheroid models closely resembling in vivo conditions and holds significantpotential for applications in drug development.

  • 3.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Khati, Vamakshi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Influence of Decellularized Extra Cellular Matrix on 3D spheroids formed on Layer-by-Layer cellulose nanofibril/Polyelectrolytes coating as an in-vitro model for Hepatocellular CarcinomaManuscript (preprint) (Other academic)
  • 4.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Lahchaichi, Ekeram
    Fayazbakhsh, Farzaneh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Tudoran, Oana
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Evaluating the Impact of Positively Charged Polyelectrolyte Molecular Weightand Bilayer Number on Tumor Spheroid Formation in the Interaction with Negatively Charged Cellulose Nanofibrils in layer by layer assembly2023Manuscript (preprint) (Other academic)
  • 5.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Lahchaichi, Ekeram
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Tudoran, Oana
    Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. I. Chiricuta”, 400015 Cluj-Napoca, Romania.
    Fayazbakhsh, Farzaneh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Heuchel, Rainer
    Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, 17177 Stockholm, Sweden.
    Löhr, Matthias
    Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, 17177 Stockholm, Sweden.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Assessing the Layer-by-Layer Assembly of Cellulose Nanofibrils and Polyelectrolytes in Pancreatic Tumor Spheroid Formation2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 11Article in journal (Refereed)
    Abstract [en]

    Three-dimensional (3D) tumor spheroids are regarded as promising models for utilization as preclinical assessments of chemo-sensitivity. However, the creation of these tumor spheroids presents challenges, given that not all tumor cell lines are able to form consistent and regular spheroids. In this context, we have developed a novel layer-by-layer coating of cellulose nanofibril–polyelectrolyte bilayers for the generation of spheroids. This technique builds bilayers of cellulose nanofibrils and polyelectrolytes and is used here to coat two distinct 96-well plate types: nontreated/non-sterilized and Nunclon Delta. In this work, we optimized the protocol aimed at generating and characterizing spheroids on difficult-to-grow pancreatic tumor cell lines. Here, diverse parameters were explored, encompassing the bilayer count (five and ten) and multiple cell-seeding concentrations (10, 100, 200, 500, and 1000 cells per well), using four pancreatic tumor cell lines—KPCT, PANC-1, MiaPaCa-2, and CFPAC-I. The evaluation includes the quantification (number of spheroids, size, and morphology) and proliferation of the produced spheroids, as well as an assessment of their viability. Notably, our findings reveal a significant influence from both the number of bilayers and the plate type used on the successful formation of spheroids. The novel and simple layer-by-layer-based coating method has the potential to offer the large-scale production of spheroids across a spectrum of tumor cell lines.

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  • 6.
    Abdollahi, Farnoosh
    et al.
    Department of Dentistry, Kashan University of Medical Science, Kashan, Iran.
    Saghatchi, Mahshid
    School of Metallurgy & Materials Engineering, Iran University of Science and Technology, Tehran, Iran.
    Paryab, Amirhosein
    Department of Materials Science & Engineering, Sharif University of Technology, Tehran, Iran.
    Malek Khachatourian, Adrine
    Department of Materials Science & Engineering, Sharif University of Technology, Tehran, Iran.
    Stephens, Emma D.
    Department of Biomedical Engineering, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada, 2500 University Drive NW.
    Toprak, Muhammet
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Badv, Maryam
    Department of Biomedical Engineering, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada, 2500 University Drive NW; Libin Cardiovascular Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada, 3330 Hospital Drive NW.
    Angiogenesis in bone tissue engineering via ceramic scaffolds: A review of concepts and recent advancements2024In: Biomaterials Advances, ISSN 2772-9516, E-ISSN 2772-9508, Vol. 159, article id 213828Article, review/survey (Refereed)
    Abstract [en]

    Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies. Different routes to angiogenesis, including chemical induction through signaling molecules immobilized covalently or non-covalently, in situ secretion of angiogenic growth factors, and the degradation of inorganic scaffolds, are described. Physical induction mechanisms are also discussed, followed by a review of methods for fabricating bioactive ceramic scaffolds via microfabrication methods, such as photolithography and 3D printing. Finally, the strengths and weaknesses of the commonly used methodologies and future directions are discussed.

  • 7.
    Abiodun Daramola, Olamide
    et al.
    Centre for Chemico- and Biomedicinal Research (CCBR), Department of Chemistry, Faculty of Science, Rhodes University, Grahamstown, South Africa; Department of Chemical and Physical Sciences, Faculty of Natural Science, Walter Sisulu University, Private Bag XI, Mthatha, South Africa.
    Bazibuhe Safari, Justin
    Centre for Chemico- and Biomedicinal Research (CCBR), Department of Chemistry, Faculty of Science, Rhodes University, Grahamstown, South Africa; Department of Pharmacy, Faculty of Pharmaceutical Sciences and Public Health, Official University of Bukavu, Bukavu, Democratic Republic Congo.
    Adeniyi, Kayode Omotayo
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Siwe-Noundou, Xavier
    Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Gauteng, Pretoria, South Africa.
    Margaret Kirkpatrick Dingle, Laura
    Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Grahamstown, South Africa.
    Lesley Edkins, Adrienne
    Biomedical Biotechnology Research Unit (BioBRU), Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Grahamstown, South Africa.
    Foster Tseki, Potlaki
    Department of Chemical and Physical Sciences, Faculty of Natural Science, Walter Sisulu University, Private Bag XI, Mthatha, South Africa.
    Werner Maçedo Krause, Rui
    Centre for Chemico- and Biomedicinal Research (CCBR), Department of Chemistry, Faculty of Science, Rhodes University, Grahamstown, South Africa.
    Biocompatible liposome and chitosan-coated CdTe/CdSe/ZnSe multi-core-multi-shell fluorescent nanoprobe for biomedical applications2024In: Journal of Photochemistry and Photobiology A: Chemistry, ISSN 1010-6030, E-ISSN 1873-2666, Vol. 454, article id 115714Article in journal (Refereed)
    Abstract [en]

    Cadmium telluride (CdTe) semiconductor quantum dots (QDs) are brightly luminescent nanocrystals that have emerged as a new class of fluorescent probes for in vivo bioimaging and theranostic applications. CdTe QDs toxicity to normal human cells is minimized by coating with a less toxic ZnS and ZnSe shell forming a core–shell nanostructure. However, coating with ZnS or ZnSe shell is insufficient to prevent the leaching of toxic Cd metal ions. To further minimize toxicity, thiol dual capped CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were coated with nanoliposome or liposome vesicles (CdTe/CdSe/ZnSe@liposome) and chitosan nanoparticles (CdTe/CdSe/ZnSe@ChitNPs) and their biocompatibility on HeLa and Vero cells were investigated. Different spectroscopic and microscopic techniques were used to elucidate nanocomposites' optical, morphological, and physicochemical properties. The coating of CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were conducted at different formulations (F1, F2 and F3) and results from the fluorescence studies show that F3 demonstrated the best interaction for both liposome and ChitNPs composite. Exposure to 12 h UV illumination studies also reveals that CdTe/CdSe/ZnSe@liposome shows an enhancement in fluorescence compared to CdTe/CdSe/ZnSe@ChitNPs. The cytotoxicity of the formulations towards HeLa and Vero cells also depicted minimal toxicity compared to CdTe/CdSe/ZnSe QDs that shows much higher toxicity (IC50 = 0.09381 mg/ml). It was further observed that liposome coated multi-core-multi-shell QDs@F2 demonstrated lower toxicity (IC50 = 0.4364 mg/ml) compared to ChitNPs coated multi-core-multi-shell QDs@F2 (IC50 = 0.1618 mg/ml). Results from the florescence imaging studies reveal that CdTe/CdSe/ZnSe-multi-core-multi-shell QDs liposomes and ChitNPs composite retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus. This indicates the successful internalization of the QDs in the cytosol. Therefore, these results shows that coating CdTe multi-core-mutli-shell QDs with liposomes and ChitNPs produce better biocompatibility compared to uncoated multi-core–shell QDs. However, liposome coated CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots show better optical properties, photostability and biocompatibility compared to CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots with ChitNPs coating. These particles therefore show good promise in cell-labelling and drug delivery studies.

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  • 8.
    Addi, Simon
    et al.
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Hedayati-Khams, Arjang
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Poya, Amin
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Sjögren, Göran
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Interface gap size of manually and CAD/CAM-manufactured ceramic inlays/onlays in vitro.2002In: Journal of Dentistry, ISSN 0300-5712, E-ISSN 1879-176X, Vol. 30, no 1, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Objectives : To determine the fit of ceramic inlays manufactured using a recently introduced CAD/CAM-system (Decim) and of two types of laboratory-made heat-pressed ceramics (IPS Empress and Opc).

    Materials and methods : Extracted human premolars were prepared to receive mesio-occlusodistal (MOD) ceramic inlays, for which 10 Denzir, 10 IPS Empress, and 10 Opc were fabricated. The Denzir restorations were produced by the manufacturer of the CAD/CAM-system, and the IPS Empress and Opc by student dental technicians. Before luting the internal fit on the diestone models and on the premolars was determined using replicas. After luting on the premolars with a resin composite the marginal and internal fit were measured. The values were analyzed statistically using ANOVA and Scheffe's test at a significance level of p<0.05.

    Results : Before luting there were no significant differences ( p>0.05) in the internal gap width between the three systems studied when placed on their matching diestone models. When placed on the premolars a significant difference ( p<0.01) in the internal fit was seen between Empress and Opc before luting, whereas there were no significant differences ( p>0.05) between Empress and Denzir and between Opc and Denzir. Between the diestone models and the premolars there were significant differences ( p<0.01) in the internal fit, except for IPS Empress. After luting there were no significant differences ( p>0.05) between IPS Empress and Denzir, whereas the marginal gap width was significantly wider ( p<0.001) for Opc than for IPS Empress and Denzir. The internal fit was significantly ( p<0.001) wider for Opc than for IPS Empress, whereas there were no significant differences ( p>0.05) between IPS Empress and Denzir or between Opc and Denzir.

    Conclusion : After luting there were only slight differences in the fit between the restorations fabricated using the three different manufacturing techniques and ceramics. Therefore, long-term follow-up studies are needed to assess the clinical significance of the slight differences between the three systems.

  • 9.
    Afewerki, Samson
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Cambridge, MA 02139 USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Bassous, Nicole
    Northeastern Univ, Dept Chem Engn, Nanomed Lab, Boston, MA 02115 USA..
    Harb, Samarah
    Sao Paulo State Univ, Inst Chem, Araraquara, SP, Brazil..
    Palo-Nieto, Carlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Ruiz-Esparza, Guillermo U.
    Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Engn Med, Cambridge, MA 02139 USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Marciano, Fernanda R.
    UFPI Fed Univ Piaui, Dept Phys, Teresina, PI, Brazil..
    Webster, Thomas J.
    Northeastern Univ, Dept Chem Engn, Nanomed Lab, Boston, MA 02115 USA..
    Aguiar Furtado, Andre Sales
    UFPI Fed Univ Piaui, Dept Mat Engn, LIMAV Interdisciplinary Lab Adv Mat, BR-64049550 Teresina, PI, Brazil..
    Lobo, Anderson O.
    UFPI Fed Univ Piaui, Dept Mat Engn, LIMAV Interdisciplinary Lab Adv Mat, BR-64049550 Teresina, PI, Brazil.;MIT, Dept Chem, Cambridge, MA 02139 USA..
    Advances in dual functional antimicrobial and osteoinductive biomaterials for orthopaedic applications2020In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 24, article id 102143Article, review/survey (Refereed)
    Abstract [en]

    A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prosthesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.

  • 10.
    Ajalloueian, Fatemeh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zeiai, Said
    Fossum, Magdalena
    Hilborn, Jöns G.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 22, p. 5741-5748Article in journal (Refereed)
    Abstract [en]

    Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.

  • 11.
    Ajaxon, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Can Bone Void Fillers Carry Load?: Behaviour of Calcium Phosphate Cements Under Different Loading Scenarios2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Calcium phosphate cements (CPCs) are used as bone void fillers and as complements to hardware in fracture fixation. The aim of this thesis was to investigate the possibilities and limitations of the CPCs’ mechanical properties, and find out if these ceramic bone cements can carry application-specific loads, alone or as part of a construct. Recently developed experimental brushite and apatite cements were found to have a significantly higher strength in compression, tension and flexion compared to the commercially available CPCs chronOS™ Inject and Norian® SRS®. By using a high-resolution measurement technique the elastic moduli of the CPCs were determined and found to be at least twice as high compared to earlier measurements, and closer to cortical bone than trabecular bone. Using the same method, Poisson's ratio for pure CPCs was determined for the first time. A non-destructive porosity measurement method for wet brushite cements was developed, and subsequently used to study the porosity increase during in vitro degradation. The compressive strength of the experimental brushite cement was still higher than that of trabecular bone after 25 weeks of degradation, showing that the cement can carry high loads over a time span sufficiently long for a fracture to heal. This thesis also presents the first ever fatigue results for acidic CPCs, and confirms the importance of testing the materials under cyclic loading as the cements may fail at stress levels much lower than the material’s quasi-static compressive strength. A decrease in fatigue life was found for brushite cements containing higher amounts of monetite. Increasing porosity and testing in a physiological buffer solution (PBS), rather than air, also decreased the fatigue life. However, the experimental brushite cement had a high probability of surviving loads found in the spine when tested in PBS, which has previously never been accomplished for acidic CPCs. In conclusion, available brushite cements may be able to carry the load alone in scenarios where the cortical shell is intact, the loading is mainly compressive, and the expected maximum stress is below 10 MPa. Under such circumstances this CPC may be the preferred choice over less biocompatible and non-degradable materials.

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  • 12.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Acciaioli, Alice
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Lionello, Giacomo
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia (UPC).
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Baleani, Massimilliano
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique2017In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 74, p. 428-437Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) should ideally have mechanical properties similar to those of the bone tissue the material is used to replace or repair. Usually, the compressive strength of the CPCs is reported and, more rarely, the elastic modulus. Conversely, scarce or no data are available on Poisson's ratio and strain-to-crack-initiation. This is unfortunate, as data on the elastic response is key to, e.g., numerical model accuracy. In this study, the compressive behaviour of brushite, monetite and apatite cements was fully characterised. Measurement of the surface strains was done using a digital image correlation (DIC) technique, and compared to results obtained with the commonly used built-in displacement measurement of the materials testers. The collected data showed that the use of fixed compression platens, as opposed to spherically seated ones, may in some cases underestimate the compressive strength by up to 40%. Also, the built-in measurements may underestimate the elastic modulus by up to 62% as compared to DIC measurements. Using DIC, the brushite cement was found to be much stiffer (24.3 ± 2.3 GPa) than the apatite (13.5 ± 1.6 GPa) and monetite (7.1 ± 1.0 GPa) cements, and elastic moduli were inversely related to the porosity of the materials. Poisson's ratio was determined to be 0.26 ± 0.02 for brushite, 0.21 ± 0.02 for apatite and 0.20 ± 0.03 for monetite. All investigated CPCs showed low strain-to-crack-initiation (0.17–0.19%). In summary, the elastic modulus of CPCs is substantially higher than previously reported and it is concluded that an accurate procedure is a prerequisite in order to properly compare the mechanical properties of different CPC formulations. It is recommended to use spherically seated platens and measuring the strain at a relevant resolution and on the specimen surface.

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  • 13.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Acciaioli, Alice
    Lionello, Giacomo
    Ginebra, Maria-Pau
    Öhman, Caroline
    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.
    Baleani, Massimiliano
    Compressive strength increase of calcium phosphate bone cements is accompanied by a stiffness increase2016Conference paper (Other academic)
  • 14.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    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.
    The influence of porosity on the fatigue properties of brushite cement2016In: Biomaterials for tissue engineering models, 2016Conference paper (Other academic)
  • 15.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    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.
    Compressive fatigue properties of a high-strength, degradable calcium phosphate bone cement – influence of porosity and environmentManuscript (preprint) (Other academic)
  • 16.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Maazouz, Yassine
    Ginebra, Maria-Pau
    Öhman, Caroline
    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.
    Evaluation of a porosity measurement method for wet calcium phosphate cements2015In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 30, no 5, p. 526-536Article in journal (Refereed)
    Abstract [en]

    The porosity of a calcium phosphate cement is a key parameter as it affects several important properties of the cement. However, a successful, non-destructive porosity measurement method that does not include drying has not yet been reported for calcium phosphate cements. The aim of this study was to evaluate isopropanol solvent exchange as such a method. Two different types of calcium phosphate cements were used, one basic (hydroxyapatite) and one acidic (brushite). The cements were allowed to set in an aqueous environment and then immersed in isopropanol and stored under three different conditions: at room temperature, at room temperature under vacuum (300 mbar) or at 37􏰀C. The specimen mass was monitored regularly. Solvent exchange took much longer time to reach steady state in hydroxyapatite cements compared to brushite cements, 350 and 18 h, respectively. Furthermore, the immersion affected the quasi-static compressive strength of the hydroxyapatite cements. However, the strength and phase composition of the brushite cements were not affected by isopropanol immersion, suggesting that isopropanol solvent exchange can be used for brushite calcium phosphate cements. The main advantages with this method are that it is non-destructive, fast, easy and the porosity can be evaluated while the cements remain wet, allowing for further analysis on the same specimen. 

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  • 17.
    Ajaxon, Ingrid
    et al.
    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.
    Mechanical Properties of Brushite Calcium Phosphate Cements2017In: The World Scientific Encyclopedia of Nanomedicine and Bioengineering II: Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and Phototherapy: Volume 3: Design of Bioactive Materials for Bone Repair and Regeneration / [ed] Shi, D., Singapore: World Scientific Pte Ltd. , 2017Chapter in book (Refereed)
  • 18.
    Ajaxon, Ingrid
    et al.
    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.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 575079Article in journal (Refereed)
    Abstract [en]

    Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material’s physical changes over a relevant time frame. 

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    Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution
  • 19.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    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.
    Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition2017In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 3, article id 41Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials. 

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  • 20.
    Akinwekomi, Akeem Damilola
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Material Science.
    Akhtar, Farid
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Material Science.
    Tunability of mechanical and biodegradation properties of zinc-based biomaterial with calcium Micronutrient alloying2023In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 140, article id 105724Article in journal (Refereed)
    Abstract [en]

    Biodegradable metals are being investigated as temporary implants that dissolve safely in the body after bone regeneration. Zinc (Zn) has an intermediate biodegradation rate between magnesium and stainless steels, yet its degradation rate is too slow to function as a temporary orthopedic implant. Alloying with nutrient elements is considered a strategy to tune its mechanical properties and in vivo biodegradability. Zn/calcium (Zn/Ca) alloys (with 0.5, 1, and 2 wt% Ca) were processed by spark plasma sintering and their microstructure, mechanical, and biodegradation properties were investigated. Ca was distributed in the grain boundary regions of Zn due to its low miscibility in Zn. Furthermore, the corrosion rates of Zn/Ca alloys determined from linear polarization measurements (0.164–0.325 mm/yr) accelerated by at least 10% compared with pure sintered Zn (0.149 mm/yr) with simultaneous dissolution of Zn and Ca, as verified from X-ray diffraction analysis of the corrosion products. The alloy specimens exhibited hardness (52–58 HV) and compressive strength (93–119 MPa) comparable with those of human cortical and cancellous bones (49 HV; 90–209 MPa). This study demonstrated the tunability of the mechanical and biodegradation properties of Zn-based materials by alloying them with a nutrient element for potential application as temporary orthopedic implants.

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  • 21. Akyuz, Lalehan
    et al.
    Kaya, Murat
    Mujtaba, Muhammad
    Ilk, Sedef
    Sargin, Idris
    Salaberria, Asier M.
    Labidi, Jalel
    Cakmak, Yavuz S.
    Islek, Cemil
    Supplementing capsaicin with chitosan-based films enhanced the anti-quorum sensing, antimicrobial, antioxidant, transparency, elasticity and hydrophobicity2018In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 115, p. 438-446Article in journal (Refereed)
  • 22.
    Alarcon, E I
    et al.
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Vulesevic, B
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Argawal, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ross, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Bejjani, P
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Podrebarac, J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ravichandran, Ranjithkumar
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Phopase, Jaywant
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Suuronen, E J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.2016In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, no 12, p. 6484-6489Article in journal (Refereed)
    Abstract [en]

    Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

  • 23.
    Allardyce, Benjamin J.
    et al.
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Rajkhowa, Rangam
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Dilley, Rodney J.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    Xie, Zhigang
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Campbell, Luke
    Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3010, Australia..
    Keating, Adrian
    Univ Western Australia, Sch Mech & Chem Engn, Nedlands, WA 6009, Australia..
    Atlas, Marcus D.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Dept ENT, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Wang, Xungai
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations2016In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 64, p. 65-74Article in journal (Refereed)
    Abstract [en]

    The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100 mu m) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing. These membranes were tested alongside animal cartilage, currently the strongest available myringoplasty graft as well as paper, which is commonly used for simpler procedures. Silk membranes showed resonant frequencies within the human hearing range and a higher vibrational amplitude than cartilage, suggesting that silk may offer good acoustic energy transfer characteristics. Silk membranes were also highly resistant to simulated pressure changes in the middle ear, suggesting they can resist retraction, a common cause of graft failure resulting from chronic negative pressures in the middle ear. Part of this strength can be explained by the substantially higher modulus of silk films compared with cartilage. This allows for the production of films that are much thinner than cartilage, with superior acoustic properties, but that still provide the same level of mechanical support as thicker cartilage. Together, these in vitro results suggest that silk membranes may provide good hearing outcomes while offering similar levels of mechanical support to the reconstructed middle ear.

  • 24.
    Alloisio, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Solid Mechanics.
    Chatziefraimidou, Marina
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Solid Mechanics.
    Roy, Joy
    KI Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden..
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Solid Mechanics.
    Fracture of porcine aorta-Part 1: symconCT fracture testing and DIC2023In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 167, p. 147-157Article in journal (Refereed)
    Abstract [en]

    Tissue failure and damage are inherent parts of vascular diseases and tightly linked to clinical events. Additionally, experimental set-ups designed to study classical engineering materials are suboptimal in the exploration of vessel wall fracture properties. The classical Compact Tension (CT) test was augmented to enable stable fracture propagation, resulting in the symmetry-constraint Compact Tension (symconCT) test, a suitable set-up for fracture testing of vascular tissue. The test was combined with Digital Image Correlation (DIC) to study tissue fracture in 45 porcine aorta specimens. Test specimens were loaded in axial and circumferential directions in a physiological solution at 37 & DEG;C. Loading the aortic vessel wall in the axial direction resulted in mode I tissue failure and a fracture path aligned with the circumferential vessel direction. Circumferential loading resulted in mode I-dominated failure with multiple deflections of the fracture path. The aorta ruptured at a principal Green-Lagrange strain of approximately 0.7, and strain rate peaks that develop ahead of the crack tip reached nearly 400 times the strain rate on average over the test specimen. It required approximately 70% more external work to fracture the aorta by circumferential than axial load; normalised with the fracture surface, similar energy levels are, however, observed. The symconCT test resulted in a stable fracture propagation, which, combined with DIC, provided a set-up for the in-depth analysis of vascular tissue failure. The high strain rates ahead of the crack tip indicate the significance of rate effects in the constitutive description of vascular tissue fracture.

  • 25.
    Alshammari, Hatem
    et al.
    Malmö University, Faculty of Odontology (OD). University of Hail, Saudi Arabia.
    Bakitian, Fahad
    Umm Al-Qura University, Saudi Arabia.
    Neilands, Jessica
    Malmö University, Faculty of Odontology (OD).
    Andersen, Ole Zoffmann
    Elos Medtech, Denmark..
    Stavropoulos, Andreas
    Malmö University, Faculty of Odontology (OD). University of Geneva, Switzerland.
    Antimicrobial Properties of Strontium Functionalized Titanium Surfaces for Oral Applications, A Systematic Review2021In: Coatings, ISSN 2079-6412, Vol. 11, no 7, article id 810Article, review/survey (Refereed)
    Abstract [en]

    The aim of this systematic review was to assess the current scientific evidence of the antimicrobial potential of strontium (Sr) when used to functionalize titanium (Ti) for oral applications. Out of an initial list of 1081 potentially relevant publications identified in three electronic databases (MEDLINE via PubMed, Scopus, and Cochrane) up to 1 February 2021, nine publications based on in vitro studies met the inclusion criteria. The antimicrobial potential of Sr was investigated on different types of functionalized Ti substrates, employing different application methods. Nine studies reported on the early, i.e., 6-24 h, and two studies on the late, i.e., 7-28 days, antimicrobial effect of Sr, primarily against Staphylococcus aureus (S. aureus) and/or Escherichia coli (E. coli). Sr-modified samples demonstrated relevant early antimicrobial potential against S. aureus in three studies; only one of which presented statistical significance values, while the other two presented only the percentage of antimicrobial rate and biofilm inhibition. A relevant late biofilm inhibition potential against S. aureus of 40% and 10%-after 7 and 14 days, respectively-was reported in one study. Combining Sr with other metal ions, i.e., silver (Ag), zinc (Zn), and fluorine (F), demonstrated a significant antimicrobial effect and biofilm inhibition against both S. aureus and E. coli. Sr ion release within the first 24 h was generally low, i.e., below 50 mu g/L and 0.6 ppm; however, sustained Sr ion release for up to 30 days, while maintaining up to 90% of its original content, was also demonstrated. Thus, in most studies included herein, Sr-functionalized Ti showed a limited immediate (i.e., 24 h) antimicrobial effect, likely due to a low Sr ion release; however, with an adequate Sr ion release, a relevant antimicrobial effect, as well as a biofilm inhibition potential against S. aureus-but not E. coli-was observed at both early and late timepoints. Future studies should assess the antimicrobial potential of Ti functionalized with Sr against multispecies biofilms associated with peri-implantitis.

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  • 26.
    Amagat, Jordi
    et al.
    Department of Biological and Chemical Engineering, Aarhus University, Denmark; Sino-Danish College (SDC), University of Chinese Academy of Sciences, Beijing 101400, China.
    Müller, Christoph Alexander
    Department of Biological and Chemical Engineering, Aarhus University, Denmark.
    Jensen, Bjarke Nørrehvedde
    Department of Biological and Chemical Engineering, Aarhus University, Denmark.
    Xiong, Xuya
    Interdisciplinary Nanoscience Center, iNANO, Aarhus University, Denmark.
    Su, Yingchun
    KTH, School of Electrical Engineering and Computer Science (EECS), Electrical Engineering, Electronics and Embedded systems, Electronic and embedded systems. Department of Biological and Chemical Engineering, Aarhus University, Denmark.
    Christensen, Natasja Porskjær
    Department of Biological and Chemical Engineering, Aarhus University, Denmark.
    Le Friec, Alice
    Department of Biological and Chemical Engineering, Aarhus University, Denmark.
    Dong, Mingdong
    Interdisciplinary Nanoscience Center, iNANO, Aarhus University, Denmark.
    Fang, Ying
    CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People's Republic of China; CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
    Chen, Menglin
    Department of Biological and Chemical Engineering, Aarhus University, Denmark; Interdisciplinary Nanoscience Center, iNANO, Aarhus University, Denmark.
    Injectable 2D flexible hydrogel sheets for optoelectrical/biochemical dual stimulation of neurons2023In: Biomaterials Advances, ISSN 2772-9516, E-ISSN 2772-9508, Vol. 146, article id 213284Article in journal (Refereed)
    Abstract [en]

    Major challenges in developing implanted neural stimulation devices are the invasiveness, complexity, and cost of the implantation procedure. Here, we report an injectable, nanofibrous 2D flexible hydrogel sheet-based neural stimulation device that can be non-invasively implanted via syringe injection for optoelectrical and biochemical dual stimulation of neuron. Specifically, methacrylated gelatin (GelMA)/alginate hydrogel nanofibers were mechanically reinforced with a poly(lactide-co-ε-caprolactone) (PLCL) core by coaxial electrospinning. The lubricant hydrogel shell enabled not only injectability, but also facile incorporation of functional nanomaterials and bioactives. The nanofibers loaded with photocatatlytic g-C3N4/GO nanoparticles were capable of stimulating neural cells via blue light, with a significant 36.3 % enhancement in neurite extension. Meanwhile, the nerve growth factor (NGF) loaded nanofibers supported a sustained release of NGF with well-maintained function to biochemically stimulate neural differentiation. We have demonstrated the capability of an injectable, hydrogel nanofibrous, neural stimulation system to support neural stimulation both optoelectrically and biochemically, which represents crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.

  • 27.
    Aminlashgari, Nina
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Höglund, Odd V
    Borg, Niklas
    Hakkarainen, Minna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Degradation profile and preliminary clinical testing of a resorbable device for ligation of blood vessels2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 6, p. 6898-904Article in journal (Refereed)
    Abstract [en]

    A resorbable device for ligation of blood vessels was developed and tested in vitro to reveal the degradation profile of the device and to predict the clinical performance in terms of adequate mechanical support during a healing period of I week. In addition, preliminary clinical testing was performed that showed complete hemostasis and good tissue grip of renal arteries in five pigs. The device was made by injection molding of poly(glycolide-co-trimethylene carbonate) triblock copolymer, and it consisted of a case with a locking mechanism connected to a partly perforated flexible band. A hydrolytic degradation study was carried out for 7, 30 and 60 days in water and buffer medium, following the changes in mass, water absorption, pH and mechanical properties. A new rapid matrix-free laser desorption ionization-mass spectrometry (LDI-MS) method was developed for direct screening of degradation products released into the degradation medium. The combination of LDI-MS and electrospray ionization-mass spectrometry analyses enabled the comparison of the degradation product patterns in water and buffer medium. The identified degradation products were rich in trimethylene carbonate units, indicating preferential hydrolysis of amorphous regions where trimethylene units are located. The crystallinity of the material was doubled after 60 days of hydrolysis, additionally confirming the preferential hydrolysis of trimethylene carbonate units and the enrichment of glycolide units in the remaining solid matrix. The mechanical performance of the perforated band was followed for the first week of hydrolysis and the results suggest that sufficient strength is retained during the healing time of the blood vessels.

  • 28. An, Rong
    et al.
    Wu, Nanhua
    Gao, Qingwei
    Dong, Yihui
    Laaksonen, Aatto
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry. Luleå University of Technology, Sweden; ‘‘Petru Poni” Institute of Macromolecular Chemistry, Romania; Nanjing Tech University, China.
    Shah, Faiz Ullah
    Ji, Xiaoyan
    Fuchs, Harald
    Integrative studies of ionic liquid interface layers: bridging experiments, theoretical models and simulations2024In: Nanoscale Horizons, ISSN 2055-6764, E-ISSN 2055-6756Article, review/survey (Refereed)
    Abstract [en]

    Ionic liquids (ILs) are a class of salts existing in the liquid state below 100 degrees C, possessing low volatility, high thermal stability as well as many highly attractive solvent and electrochemical capabilities, etc., making them highly tunable for a great variety of applications, such as lubricants, electrolytes, and soft functional materials. In many applications, ILs are first either physi- or chemisorbed on a solid surface to successively create more functional materials. The functions of ILs at solid surfaces can differ considerably from those of bulk ILs, mainly due to distinct interfacial layers with tunable structures resulting in new ionic liquid interface layer properties and enhanced performance. Due to an almost infinite number of possible combinations among the cations and anions to form ILs, the diversity of various solid surfaces, as well as different external conditions and stimuli, a detailed molecular-level understanding of their structure-property relationship is of utmost significance for a judicious design of IL-solid interfaces with appropriate properties for task-specific applications. Many experimental techniques, such as atomic force microscopy, surface force apparatus, and so on, have been used for studying the ion structuring of the IL interface layer. Molecular Dynamics simulations have been widely used to investigate the microscopic behavior of the IL interface layer. To interpret and clarify the IL structure and dynamics as well as to predict their properties, it is always beneficial to combine both experiments and simulations as close as possible. In another theoretical model development to bridge the structure and properties of the IL interface layer with performance, thermodynamic prediction & property modeling has been demonstrated as an effective tool to add the properties and function of the studied nanomaterials. Herein, we present recent findings from applying the multiscale triangle experiment-simulation-thermodynamic modeling in the studies of ion structuring of ILs in the vicinity of solid surfaces, as well as how it qualitatively and quantitatively correlates to the overall ILs properties, performance, and function. We introduce the most common techniques behind experiment-simulation-thermodynamic modeling and how they are applied for studying the IL interface layer structuring, and we highlight the possibilities of the IL interface layer structuring in applications such as lubrication and energy storage. Integrative experiment-simulation-thermodynamic modeling is highly demanded for qualitatively and quantitatively correlating the ionic liquids interface layer structuring to the overall properties, performance, and function.

  • 29.
    Andersson, Marlene
    et al.
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Jia, Qiupin
    Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, P.R. China..
    Abella, Ana
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Lee, Xiau-Yeen
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Landreh, Michael
    Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK..
    Purhonen, Pasi
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden..
    Hebert, Hans
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden..
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Biomedical Engineering, Lund University, Lund, Sweden..
    Robinson, Carol V.
    Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK..
    Meng, Qing
    Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, P.R. China..
    Plaza, Gustavo R.
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Johansson, Jan
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.; Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.; Karolinska Institutet.
    Rising, Anna
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.;Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.; Karolinska Institutet.
    Biomimetic spinning of artificial spider silk from a chimeric minispidroin2017In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, no 3, p. 262-264Article in journal (Refereed)
    Abstract [en]

    Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.

  • 30.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.

    The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.

    By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.

    The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery

    .

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  • 31.
    Aronsson, Henrik
    Linköping University, The Department of Physics, Chemistry and Biology.
    Local Delivery of Bisphosphonates from FibMat Matrix2008Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    Improving the functionality and reducing revision rates are important driving forces in the development of orthopaedic implants. FibMat is a fibrinogen based matrix developed towards commercialisation by the company Optovent AB. This matrix can be coated on implants and act as a local drug delivery system for bisphosphonates (BPs). BPs are drugs inhibiting bone resorption, and applied with FibMat to improve stability of implants in bone, e.g. when fixing bone fractures. In this thesis, FibMat loaded with BP (FibMat/BP) was coated on stainless-steel screws and titanium screws in order to investigate some technology properties relevant to its clinical applicability. Bone-mimicking materials were used to study scrape-off effect upon insertion. The coagulation properties of fibrinogen as well as the structural properties of BPs were studied after exposure to gamma radiation.

    The screws were coated with FibMat and BP (alendronate and 14C-alendronate) using standard coupling techniques. The total amount and distribution of BP after insertion was measured by liquid scintillation and autoradiography. Coagulation assays were performed in order to determine the coagulation properties of fibrinogen, exposed to doses up to 35 kGy, mixed with thrombin. The structural properties of four different BPs (alendronate, pamidronate, zoledronate and ibandronate), exposed to doses up to 35 kGy were analysed by transmission infrared spectroscopy.

    The results show that FibMat/BP coating on porous stainless-steel screws is virtually unaffected by insertion into bone materials. The anodised, planar titanium screws are more affected by the insertion process, but an even BP distribution in the cancellous material is indicated. The coagulation assays show that gamma-irradiated fibrinogen has a slower coagulation process compared to non-irradiated fibrinogen and form interrupted network unable to clot. The chemical structures of the BPs seem unaffected by exposure to gamma irradiation. In conclusion, the FibMat/BP is a promising technology for local distribution of BP in conjunction with bone implants.

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  • 32.
    Arza, Carlos R.
    et al.
    Lund University;Centre for Analysis and Synthesis;SE-22100 Lund;Sweden.
    İlk, Sedef
    Ömer Halisdemir University;Central Research Laboratory;Niğde;Turkey.
    Demircan, Deniz
    Lund University;Centre for Analysis and Synthesis;SE-22100 Lund;Sweden.
    Zhang, Baozhong
    Lund University;Centre for Analysis and Synthesis;SE-22100 Lund;Sweden.
    New biobased non-ionic hyperbranched polymers as environmentally friendly antibacterial additives for biopolymers2018In: Green Chemistry, ISSN 1463-9262, E-ISSN 1463-9270, Vol. 20, no 6, p. 1238-1249Article in journal (Refereed)
  • 33.
    Asawa, Kenta
    et al.
    Univ Tokyo, Sch Engn, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Ishihara, Kazuhiko
    Univ Tokyo, Sch Engn, Dept Mat Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Tokyo, Sch Engn, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Cell Surface Functionalization with Heparin-Conjugated Lipid to Suppress Blood Activation2021In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 31, no 11, article id 2008167Article in journal (Refereed)
    Abstract [en]

    Organ transplantation leads to damage of the endothelial glycocalyx of the transplanted organ, and the activated endothelial surface induces thromboinflammation. The result is dysfunction of the transplanted organ, known as ischemia reperfusion injury (IRI). Long-term graft survival strongly depends on the regulation of IRI. Here the aim is to reconstruct the glycocalyx to regulate blood activation during IRI. Heparin-conjugated lipid (fHep-lipid) is synthesized with 0.6, 1.8, 2.7, 4.5, or 8.0 fragmented heparins per lipid to compare their anticoagulation activity. First, liposome and cells are modified with each fHep-lipid and the surface properties are evaluated. Then the hemocompatibility of the modified human mesenchymal stem cells (hMSCs) is examined in a loop model using human blood. The antithrombin-binding capacity and anti-factor Xa activity of the fHep-lipids depend on the number of conjugated heparins, with efficacy increasing with increasing number of heparins. The modified liposomes are highly negatively charged and show strong anti-factor Xa activity. In addition, the cell surfaces of human erythrocytes and hMSCs can be uniformly modified with fHep-lipid. The whole blood studies reveal that fHep-lipid on hMSCs can prevent generation of thrombin-antithrombin complexes, coagulation markers, and platelet aggregation, whereas unmodified hMSCs trigger activation of the platelet and coagulation systems.

  • 34.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Asawa, Kenta
    Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
    Yuuki, Inoue
    Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
    Ishihara, Kazuhiko
    Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
    Lindell, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Holmgren, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ryden, Anneli
    Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Almas Allé 8, 750 07 Uppsala, Sweden.
    Jensen-Waern, Marianne
    Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Almas Allé 8, 750 07 Uppsala, Sweden.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Department of Bioengineering, The University of Tokyo, Tokyo, Japan.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.
    Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models2019In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, no 5, article id 1800485Article in journal (Refereed)
    Abstract [en]

    Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.

  • 35.
    Asif, Sana
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Fromell, Karin
    Uppsala University.
    Gustafson, Elisabet
    Uppsala University Hospital.
    Barbu, Andreea
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet;Karolinska University Hospital.
    Nilsson, Bo
    Uppsala University.
    Teramura, Yuji
    Uppsala University;The University of Tokyo, Japan.
    Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 36.
    Atefyekta, Saba
    et al.
    Chalmers Univ Technol, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden.
    Blomstrand, Edvin
    Chalmers Univ Technol, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden.
    Rajasekharan, Anand K.
    Chalmers Univ Technol, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden.
    Svensson, Sara
    Univ Gothenburg, Dept Biomat, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.
    Trobos, Margarita
    Univ Gothenburg, Dept Biomat, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden; Univ Gothenburg, Ctr Antibiot Resistance Res CARe, SE-40530 Gothenburg, Sweden.
    Hong, Jaan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Webster, Thomas J.
    Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA.
    Thomsen, Peter
    Univ Gothenburg, Dept Biomat, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.
    Andersson, Martin
    Chalmers Univ Technol, Dept Chem & Chem Engn, SE-41296 Gothenburg, Sweden.
    Antimicrobial Peptide-Functionalized Mesoporous Hydrogels2021In: ACS Biomaterials Science & Engineering, E-ISSN 2373-9878, Vol. 7, no 4, p. 1693-1702Article in journal (Refereed)
    Abstract [en]

    Antimicrobial peptides (AMPs) are seen as a promising replacement to conventional antibiotics for the prevention of skin wound infections. However, due to the short half-life of AMPs in biological environments, such as blood, their use in clinical applications has been limited. The covalent immobilization of AMPs onto suitable substrates is an effective solution to create contact-killing surfaces with increased long-term stability. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was covalently attached to amphiphilic and ordered mesoporous Pluronic F127 hydrogels made of cross-linked lyotropic liquid crystals through 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. The AMP-hydrogels showed high antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), and multidrug-resistant Escherichia coli for up to 24 h. Furthermore, the AMP-hydrogels did not present any toxicity to human fibroblasts. The AMPs retained their antimicrobial activity up to 48 h in human blood serum, which is a significant increase in stability compared to when used in dissolved state. A pilot in vivo rat model showed 10–100× less viable counts of S. aureus on AMP-hydrogels compared with control hydrogels during the first 3 days of infection. Studies performed on human whole blood showed that blood coagulated more readily in the presence of AMP-hydrogels as compared to hydrogels without AMPs, indicating potential hemostatic activity. Overall, the results suggest that the combination of amphiphilic hydrogels with covalently bonded AMPs has potential to be used as antibacterial wound dressing material to reduce infections and promote hemostatic activity as an alternative to antibiotics or other antimicrobial agents, whose use should be restricted.

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  • 37.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Tenje, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Microsystems Technology.
    A microfluidics-based method for culturing osteoblasts on biomimetic hydroxyapatite2021In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 127, p. 327-337Article in journal (Refereed)
    Abstract [en]

    The reliability of conventional cell culture studies to evaluate biomaterials is often questioned, as in vitro outcomes may contradict results obtained through in vivo assays. Microfluidics technology has the potential to reproduce complex physiological conditions by allowing for fine control of microscale features such as cell confinement and flow rate. Having a continuous flow during cell culture is especially advantageous for bioactive biomaterials such as calcium-deficient hydroxyapatite (HA), which may otherwise alter medium composition and jeopardize cell viability, potentially producing false negative results in vitro. In this work, HA was integrated into a microfluidics-based platform (HA-on-chip) and the effect of varied flow rates (2, 8 and 14 µl/min, corresponding to 0.002, 0.008 and 0.014 dyn/cm2, respectively) was evaluated. A HA sample placed in a well plate (HA-static) was included as a control. While substantial calcium depletion and phosphate release occurred in static conditions, the concentration of ions in HA-on-chip samples remained similar to those of fresh medium, particularly at higher flow rates. Pre-osteoblast-like cells (MC3T3-E1) exhibited a significantly higher degree of proliferation on HA-on-chip (8 μl/min flow rate) as compared to HA-static. However, cell differentiation, analysed by alkaline phosphatase (ALP) activity, showed low values in both conditions. This study indicates that cells respond differently when cultured on HA under flow compared to static conditions, which indicates the need for more physiologically relevant methods to increase the predictive value of in vitro studies used to evaluate biomaterials.

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  • 38.
    Aulin, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Extracellular Matrix Based Materials for Tissue Engineering2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition.

    The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.

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  • 39. Azinas, S.
    et al.
    Bano, F.
    Torca, I.
    Bamford, D. H.
    Schwartz, G. A.
    Esnaola, J.
    Oksanen, H. M.
    Richter, R. P.
    Abrescia, N. G.
    Membrane-containing virus particles exhibit the mechanics of a composite material for genome protection2018In: Nanoscale, Vol. 10, no 16, p. 7769-7779Article in journal (Refereed)
  • 40.
    Bai, Xuan
    et al.
    Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Dept Cariol & Endodont, Chengdu 610041, Peoples R China..
    Liu, Wenjuan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science. Hunan Univ Sci & Technol, Sch Mat Sci & Engn, Xiangtan 411201, Peoples R China.;Hunan Univ Sci & Technol, Hunan Prov Key Lab Controllable Preparat & Funct, Xiangtan 411201, Peoples R China..
    Xu, Laijun
    Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Dept Cariol & Endodont, Chengdu 610041, Peoples R China..
    Ye, Qing
    Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Dept Cariol & Endodont, Chengdu 610041, Peoples R China..
    Zhou, Huasi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Berg, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Yuan, He
    Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China..
    Li, Jiyao
    Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Hosp Stomatol, Dept Cariol & Endodont, Chengdu 610041, Peoples R China..
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Sequential macrophage transition facilitates endogenous bone regeneration induced by Zn-doped porous microcrystalline bioactive glass2021In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 9, no 12, p. 2885-2898Article in journal (Refereed)
    Abstract [en]

    Macrophages play an important role in the immune microenvironment during bone healing, and sequential macrophage phenotypic transition could achieve superior osteogenic outcomes. Microcrystalline bioactive glasses (MCBGs) with osteoimmunomodulatory effects show potential in bone tissue regeneration. Zinc (Zn) has been approved to coordinate innate and adaptive immunity. Therefore, in this study, different amounts of ZnO were incorporated into microcrystalline bioactive glass to improve its immunomodulatory ability. The effect of Zn-MCBG ionic extracts on macrophage transition was studied, and the 5Zn-MCBG extracts could orchestrate sequential M1-to-M2 macrophage transition and promote the expression of proinflammatory and anti-inflammatory genes and cytokine expression to induce human bone marrow stromal cells (hBMSCs) osteogenic differentiation in vitro. Macroporous Zn-MCBG scaffolds containing mesopores were fabricated and showed good cell adhesion and feasible apatite formation when immersed in SBF in vitro. Furthermore, a rat calvarial defect model was used to confirm that the Zn-MCBG scaffold could modulate macrophage phenotypic transition and create a desirable osteogenic microenvironment to promote osteogenesis in vivo.

  • 41.
    Bajic, Andrej
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.
    Andersson, Brittmarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.
    Ossinger, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.
    Tavakoli, Shima
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Macromolecular Chemistry.
    Varghese, Oommen P.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Macromolecular Chemistry.
    Schizas, Nikos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics and Handsurgery.
    Physically and Chemically Crosslinked Hyaluronic Acid-Based Hydrogels Differentially Promote Axonal Outgrowth from Neural Tissue Cultures2024In: Biomimetics, E-ISSN 2313-7673, Vol. 9, no 3, article id 140Article in journal (Refereed)
    Abstract [en]

    Our aim was to investigate axonal outgrowth from different tissue models on soft biomaterials based on hyaluronic acid (HA). We hypothesized that HA-based hydrogels differentially promote axonal outgrowth from different neural tissues. Spinal cord sliced cultures (SCSCs) and dorsal root ganglion cultures (DRGCs) were maintained on a collagen gel, a physically crosslinked HA-based hydrogel (Healon 5®) and a novel chemically crosslinked HA-based hydrogel, with or without the presence of neurotrophic factors (NF). Time-lapse microscopy was performed after two, five and eight days, where axonal outgrowth was assessed by automated image analysis. Neuroprotection was investigated by PCR. Outgrowth was observed in all groups; however, in the collagen group, it was scarce. At the middle timepoint, outgrowth from SCSCs was superior in both HA-based groups compared to collagen, regardless of the presence of NF. In DRGCs, the outgrowth in Healon 5® with NF was significantly higher compared to the rest of the groups. PCR revealed upregulation of NeuN gene expression in the HA-based groups compared to controls after excitotoxic injury. The differences in neurite outgrowth from the two different tissue models suggest that axons differentially respond to the two types of biomaterials.

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  • 42.
    Balion, Zbigniev
    et al.
    Lithuanian Univ Hlth Sci, Inst Pharmaceut Technol, Sukileliu Ave 13, LT-50162 Kaunas, Lithuania.;Lithuanian Univ Hlth Sci, Neurosci Inst, Eiveniu Str 4, LT-50161 Kaunas, Lithuania..
    Cepla, Vytautas
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania.;Ctr Phys Sci & Technol, Dept Nanoengn, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Svirskiene, Natasa
    Lithuanian Univ Hlth Sci, Neurosci Inst, Eiveniu Str 4, LT-50161 Kaunas, Lithuania..
    Svirskis, Gytis
    Lithuanian Univ Hlth Sci, Neurosci Inst, Eiveniu Str 4, LT-50161 Kaunas, Lithuania..
    Druceikaite, Kristina
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Inokaitis, Hermanas
    Lithuanian Univ Hlth Sci, Inst Anat, Mickeviciaus 9, LT-43074 Kaunas, Lithuania..
    Rusteikaite, Justina
    Lithuanian Univ Hlth Sci, Inst Pharmaceut Technol, Sukileliu Ave 13, LT-50162 Kaunas, Lithuania..
    Masilionis, Ignas
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Stankeviciene, Gintare
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania.;Ctr Phys Sci & Technol, Dept Nanoengn, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Jelinskas, Tadas
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Ulcinas, Arturas
    Ctr Phys Sci & Technol, Dept Nanoengn, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Samanta, Ayan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Valiokas, Ramunas
    Ferentis UAB, Savanoriu 231, LT-02300 Vilnius, Lithuania.;Ctr Phys Sci & Technol, Dept Nanoengn, Savanoriu 231, LT-02300 Vilnius, Lithuania..
    Jekabsone, Aiste
    Lithuanian Univ Hlth Sci, Inst Pharmaceut Technol, Sukileliu Ave 13, LT-50162 Kaunas, Lithuania.;Lithuanian Univ Hlth Sci, Neurosci Inst, Eiveniu Str 4, LT-50161 Kaunas, Lithuania..
    Cerebellar Cells Self-Assemble into Functional Organoids on Synthetic, Chemically Crosslinked ECM-Mimicking Peptide Hydrogels2020In: Biomolecules, E-ISSN 2218-273X, Vol. 10, no 5, article id 754Article in journal (Refereed)
    Abstract [en]

    Hydrogel-supported neural cell cultures are more in vivo-relevant compared to monolayers formed on glass or plastic substrates. However, there is a lack of synthetic microenvironment available for obtaining standardized and easily reproducible cultures characterized by tissue-mimicking cell composition, cell-cell interactions, and functional networks. Synthetic peptides representing the biological properties of the extracellular matrix (ECM) proteins have been reported to promote the adhesion-driven differentiation and functional maturation of neural cells. Thus, such peptides can serve as building blocks for engineering a standardized, all-synthetic environment. In this study, we have compared the effect of two chemically crosslinked hydrogel compositions on primary cerebellar cells: collagen-like peptide (CLP), and CLP with an integrin-binding motif arginine-glycine-aspartate (CLP-RGD), both conjugated to polyethylene glycol molecular templates (PEG-CLP and PEG-CLP-RGD, respectively) and fabricated as self-supporting membranes. Both compositions promoted a spontaneous organization of primary cerebellar cells into tissue-like clusters with fast-rising Ca2+ signals in soma, reflecting action potential generation. Notably, neurons on PEG-CLP-RGD had more neurites and better synaptic efficiency compared to PEG-CLP. For comparison, poly-L-lysine-coated glass and plastic surfaces did not induce formation of such spontaneously active networks. Additionally, contrary to the hydrogel membranes, glass substrates functionalized with PEG-CLP and PEG-CLP-RGD did not sufficiently support cell attachment and, subsequently, did not promote functional cluster formation. These results indicate that not only chemical composition but also the hydrogel structure and viscoelasticity are essential for bioactive signaling. The synthetic strategy based on ECM-mimicking, multifunctional blocks in registry with chemical crosslinking for obtaining tissue-like mechanical properties is promising for the development of fast and well standardized functional in vitro neural models and new regenerative therapies.

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  • 43.
    Ballo, Ahmed
    et al.
    Gothenburg University.
    Omar, Omar
    Gothenburg Univerity.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Palmquist, Anders
    Gothenburg University.
    Dental Implant Surfaces Implant Dentistry - A Rapidly Evolving Practic: Physicochemical Properties, Biological Performance, and Trends2011In: Implant Dentistry: A Rapidly Evolving Practice / [ed] Ilser Turkyilmaz, INTECH , 2011Chapter in book (Refereed)
  • 44.
    Bang, Le T.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Filho, Luimar
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants2020In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 108, no 2, p. 429-438Article in journal (Refereed)
    Abstract [en]

    Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti-6Al-4V alloy through a hydrothermal treatment of previously NaOH-treated surfaces in calcium-citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170 degrees C for 3 hr. The coating was approx. 1 mu m thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated- and un-coated samples. However, the CaCO3 coating reduced by approx. 2-5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO3 and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO3 coating encourage further studies on this coating for clinical applications.

  • 45.
    Bano, Fouzia
    et al.
    CIC biomaGUNE, Donostia-San Sebastian, Spain.
    Banerji, Suneale
    Howarth, Mark
    Jackson, David G.
    Richter, Ralf P.
    A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 34176Article in journal (Refereed)
    Abstract [en]

    Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

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  • 46.
    Bano, Fouzia
    et al.
    CIC biomaGUNE, Donostia - San Sebastian, Spain.
    Carril, Mónica
    Di Gianvincenzo, Paolo
    Richter, Ralf P.
    Interaction of hyaluronan with cationic nanoparticles2015In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 31, no 30, p. 8411-8420Article in journal (Refereed)
    Abstract [en]

    The polysaccharide hyaluronan (HA) is a main component of peri- and extracellular matrix, and an attractive molecule for materials design in tissue engineering and nanomedicine. Here, we study the morphology of complexes that form upon interaction of nanometer-sized amine-coated gold particles with this anionic, linear, and regular biopolymer in solution and grafted to a surface. We find that cationic nanoparticles (NPs) have profound effects on HA morphology on the molecular and supramolecular scale. Quartz crystal microbalance (QCM-D) shows that depending on their relative abundance, cationic NPs promote either strong compaction or swelling of films of surface-grafted HA polymers (HA brushes). Transmission electron and atomic force microscopy reveal that the NPs do also give rise to complexes of distinct morphologies–compact nanoscopic spheres and extended microscopic fibers–upon interaction with HA polymers in solution. In particular, stable and hydrated spherical complexes of single HA polymers with NPs can be prepared when balancing the ionizable groups on HA and NPs. The observed self-assembly phenomena could be useful for the design of drug delivery vehicles and a better understanding of the reorganization of HA-rich synthetic or biological matrices.

  • 47.
    Bano, Fouzia
    et al.
    University of Liège, Department of Chemistry, Belgium.
    Sluysmans, D.
    Wislez, A.
    Duwez, A. -S
    Unraveling the complexity of the interactions of DNA nucleotides with gold by single molecule force spectroscopy2015In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 7, no 46, p. 19528-19533Article in journal (Refereed)
    Abstract [en]

    Addressing the effect of different environmental factors on the adsorption of DNA to solid supports is critical for the development of robust miniaturized devices for applications ranging from biosensors to next generation molecular technology. Most of the time, thiol-based chemistry is used to anchor DNA on gold – a substrate commonly used in nanotechnology – and little is known about the direct interaction between DNA and gold. So far there have been no systematic studies on the direct adsorption behavior of the deoxyribonucleotides (i.e., a nitrogenous base, a deoxyribose sugar, and a phosphate group) and on the factors that govern the DNA–gold bond strength. Here, using single molecule force spectroscopy, we investigated the interaction of the four individual nucleotides, adenine, guanine, cytosine, and thymine, with gold. Experiments were performed in three salinity conditions and two surface dwell times to reveal the factors that influence nucleotide–Au bond strength. Force data show that, at physiological ionic strength, adenine–Au interactions are stronger, asymmetrical and independent of surface dwell time as compared to cytosine–Au and guanine–Au interactions. We suggest that in these conditions only adenine is able to chemisorb on gold. A decrease of the ionic strength significantly increases the bond strength for all nucleotides. We show that moderate ionic strength along with longer surface dwell period suggest weak chemisorption also for cytosine and guanine.

  • 48.
    Bano, Fouzia
    et al.
    School of Biomedical Sciences, Faculty of Biological Sciences, School of Physics and Astronomy, Faculty of Mathematics and Physical Sciences, and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; CIC biomaGUNE, Biosurfaces Laboratory, Donostia-San Sebastian, Spain.
    Tammi, M. I.
    Kang, D. W.
    Harris, E. N.
    Richter, R. P.
    Single-molecule unbinding forces between the polysaccharide hyaluronan and its binding proteins2018In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 114, no 12, p. 2910-2922Article in journal (Refereed)
    Abstract [en]

    The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices.

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  • 49.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Montufar, Edgar
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Öhman, Caroline
    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.
    Fontecha, Pedro
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 79, p. 135-147Article in journal (Refereed)
    Abstract [en]

    There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.

  • 50.
    Basu, Alex
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Celma, Gunta
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ion-crosslinked nanocellulose hydrogels promote wound healing in vitro and in vivo2019In: Scandinavian Society for Biomaterials Conference 2019 / [ed] Scandinavian Society for Biomaterials, 2019Conference paper (Refereed)
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