BIOFILMS RESEARCH CENTER FOR BIOINTERFACES€¦ · happy that Michael Braian became Swedish champion in explaining his research and won the competition Forskar Grand Prix organized

BIOFILMSRESEARCH CENTER FOR BIOINTERFACES

AnnuAl RepoRt 2014

MALMÖ UNIVERSITYBIOFILMS – RESEARCH CENTER FOR BIOINTERFACES

Biofilms – Research Center for Biointerfaces

Annual Report 2014

Biofilms – Research Center for Biointerfaces (BRCB) is a translational research center

covering four research groups within

three faculties at Malmö University. The

core strengths of the Center are our broad

expertise, spanning the whole range from

theoretical modelling to clinical sciences,

and our long experience in working with

industry and relating to their needs. The

general aim of research activities at the

Center is to understand, predict and control

material/cell/tissue interactions with medical,

dental, food and environmental applications.

BRCB aims to become a regional site for

a creative biomedical technology environ

ment in the Öresund region, facilitating

collaboration between academic research,

higher education and industry, based on

pharmaceutical technology, biotechnology

and medical technology. Together, they

form a key area that offers significant

commercial growth potential. We are

striving to become a prime entry point

for regional industry seeking translational

academic expertise in the biomedical

technology field.

CENTER MISSION STATEMENT

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Annual Report 2014

DIRECTOR’S REpORT 4

NEwS 2014 5

wORkSHOpS AND CONFERENCES ORgANISED By THE CENTER

10

RESEARCH HIgHLIgHTS 12

LIST OF CENTER MEMBERS 26

LIST OF RESEARCH ACTIvITIES

30

SCIENTIFIC INSTRuMENTATION AND EquIpMENT

34

COLLABORATIvE pARTNERS OF THE CENTER

41

pHD THESES SupERvISED By CENTER MEMBERS

47

LIST OF puBLICATIONS AT THE CENTER FROM 2014

50

CONTRIBuTIONS TO AND pARTICIpATION IN CONFERENCES AND wORkSHOpS

57

front illustration: Histological section of the bone to implant interface (Johansson p., Jimbo R., kjellin p., Currie F., Chrcanovic B., wennerberg A.Johansson, Biomechanical evaluation and surface characterization of a nano-modified surface on pEEk implants: a study in the rabbit tibia, Int J Nanomedicine. 2014 Aug 14;9:3903–11)

CONTENTS

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Annual Report 2014

DIRECTOR’S REpORT

2014 was a busy year for the Center and operations developed positively on many fronts. The administration staff at the Center and the Biomedical Sciences Research Group are both now in place in the new laboratory facilities adjacent to Medeon Science Park in Malmö and they are fully immersed in establishing a biomedical technology arena that will facilitate collaboration between academic research, higher education and industry. The goal is to create an innovation centre where researchers, students and entrepreneurs work side by side and share equipment and laboratories.

It has also been a year with the focus on PhD dissertations. Magnus Falk, Deyar Mahmood, Marjan Dorkhan, Ramesh Chowdhart, Anton Fagerström, Peter Lamberg, and Vida Krikstolaityte (Vilnius University), all successfully defended their PhD theses during the year. We are especially proud that Yana Znamenskaya’s thesis from 2013 “Effect of Hydration on Thermodynamic, Rheological and Structural Properties of Mucin” was awarded a prize at Malmö University’s Annual Ceremony in 2014 and that Marjan Dorkhan’s thesis “Effect of surface characteristics on cellular adherence and activity” was awarded the prize for the thesis of the year at the Faculty of Odontology. We are also happy that Michael Braian became Swedish champion in explaining his research and won the competition Forskar Grand Prix organized by the Swedish Research Council, Formas, Forte and VINNOVA.

When it comes to cooperation with industry, 2014 has been an exciting year. We successfully established new research collaborations with both local and inter national industrial

companies and enhanced research collaboration with Camurus AB and CR Competence AB by appointing Justas Barauskas and Tobias Haltur as adjunct researchers.

During 2014, we had a portfolio of 33 re search projects and collaborated with 33 different companies. We produced around 90 scientific publications in peerreviewed scientific journals and researchers at the Center actively contributed to the national and international research communities through involvement in organising international meetings, including the 15th International Conference on Electroanalysis, the 8th International Conference on Molecular Imprinting and the 10th Annual Workshop of Biofilms – Research Center for Biointerfaces. Other contributions to the research community have been made through membership of editorial and scientific advisory boards and as guest editors for highly reputed inter national journals, such as ‘Acta Biomaterialia’, ‘International Journal of Prosthodontics and Restorative Dentistry’, ‘American Journal of Dentistry, ‘ScienceJet’, ‘PeerJ’, Biosensors and Bioelectronics, and ‘Nonlinear Analysis: Modelling and Control’.

Finally, I would like to thank all those with whom we have worked for their invaluable contribution during the past year as well as Malmö University for its consistent support. I would also like to thank the Knowledge Foundation, the Swedish Research Council, the Borrow Foundation, the Swedish Laryng Foundation, the European Commission, the Skåne Region, the Crafoord Foundation, the British Medical Research Council and the Gustaf Th. Ohlsson Foundation who have funded our research.

Anna Holmberg, Director Biofilms

– Research Center for Biointerfaces

Interview with Michael Braian at http://www.tv4.se/nyhetsmorgon/klipp/han-vann-forskar-grand-prix-tack-vare-3d-t%C3%A4nder-3019489

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Annual Report 2014

NEwS 2014

The new BRCB premises are bursting with activity now that researchers and students from the Department of Biomedical Science and the Center administration staff have moved in. The laboratories, which are adjacent to Medeon Science Park, are wellequipped with advanced instruments and firstrate analytical equipment. The researchers now have access to instruments such as AFM, DSC, Ellipsometers, LCMS, NMR, SEM, Sorption Calorimeter, In vitro Diffusion Equipment and QCMD.

“Our aim is to create an innovation centre where students, researchers, entrepreneurs

and companies work side by side, sharing equipment and laboratories,” said Anna Holmberg, Director.

“We hope to achieve our goal of becoming a regional meeting point and a creative environment for biomedical technology in the Öresund region, facilitating collaboration between academia, higher education and industry, based on pharmaceutical techno logy, biotechnology and medical technology. We are striving to become a prime entry point for regional industry seeking translational academic expertise in the biomedical technology field.”

new pRemises set to become An innovAtion centRe

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Annual Report 2014

3. new ReseARch will incReAse knowledge of AtheRoscleRosisResearcher Marité Cárdenas Gómez at the Department of Biomedical Science has been granted SEK 8 million by the Swedish Research Council for a new research project, ‘Lipoprotein structure in the bulk and at the surface of vessel wall components’.

“We will study the structure of different lipoprotein particles. Lipoprotein is a biochemical assembly that contains both proteins

and lipids. The particles will be studied in solution and at the interface with the vessel wall,” she said.

By increasing knowledge of the structure and what takes place when lipoprotein is bound at the vessel wall, researchers hope to eventually come one step closer to developing diagnostics and treatment for atherosclerosis.

thesis of the YeAR 2014

Yana Znamenskaya was one of the prize winners at 2014 Annual Awards Ceremony, receiving the Thesis of the Year Award.

“I am very happy and proud to be honoured with the thesis of the year,” said Yana Znamenskaya. “The Department of Biomedical Science is an incredible research environment with high scientific standards and broad research field! I have had a great and professional supervision during my PhD study; without it nothing would be possible!”

THESIS ABOUT MUCUS

Yana Znamenskaya’s thesis “Effect of Hydration on Thermodynamic, Rheological and Structural Properties of Mucin” is focused on understanding of how the properties of the mucus change under different conditions, which is relevant for biomaterial coatings and drug delivery applications.

INCREASED RISk OF DISEASE

Mucus is a hydrated layer covering the epi thelium and is found in all internal tracts in the body – in the nose, mouth, stomach and intestines for example. One of its most essential functions is to protect the under lying tissue against dehydration, thus explaining why it contains large amounts of water. However, if the mucus comes into contact with dry air over a long period, it begins to dehydrate, reducing its protective properties and increasing the risk of disease.

MUCIN – A COMpLEx MOLECULE

In order to understand how mucus works,

Yana Znamenskaya made a study of its components. “The main component that is responsible for the protective properties of mucus is mucin, a complex molecule that we know very little about. This applies in particular to the very limited knowledge we have of how its properties are affected by hydration.”

“To investigate the fundamental properties of native tissues, especially how the highly hydrated layer covering mucosal surfaces of our body is affected by changes in ambient condition, I have studied how the mucin system is affected when the level of hydration and the temperature are changed.

SEVERAL AREAS OF USE

Yana Znamenskaya employed a whole series of methods and techniques in her research and she presents what are termed hydration curves, which describe how much water mucin can uptake at different hydration levels and temperatures. She also shows the conditions under which the transition from a glassy to an elastic state takes place.

“It is a complex system and we still have a great deal to learn although I hope that my research will be of use, for example, in enhancing transmucosal drug delivery and coatings of biomaterials.”

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Annual Report 2014

ReseARch cAn contRibute to the eARlY discoveRY of dementiAProfessor Börje Sellergren has been granted funds by the Swedish Research Council for a research project dealing with diagnostic tools for neurodegenerative disease markers. The research involves developing tools for analysing lipidbased and proteinbased biomarkers in order to identify patients with cognitive neurological diseases before symptoms appear.

Apart from their wellknown structural function as a primary component in cell membranes, lipids have a whole range of biological functions and it has been shown that their existence in body fluids could reflect specific disorders, such as Alzheimer’s disease. However, at present there is an absence of practical methods for measuring these biomarkers clinically.

As part of an ongoing project, the research group has developed a highly sensitive method for the detection of very low lipid levels. In the new project, they will be able to use this method for the analysis of bioactive lipids in order to identify new biomarkers and to develop a specific, sensitive and rapid testing method for bloodbased lipid biomarkers.

“The aim is to develop new methods for the analysis of these biomarkers and for these methods to be brought into clinical use,” said Börje Sellergren. “The opportunity to reliably discover clinically accepted biomarkers for small vessel diseases and Alzheimer’s disease in the blood instead of cerebral fluid would simplify diagnostic procedures considerably. This would cut costs and involve fewer and less invasive interventions for the patient.”

Together with her research colleagues, Marité Cárdenas Gómez will produce biomimetic surfaces – surfaces that are designed using a special technique to represent biological surfaces. The researchers will attach different components from the vessel wall, which

is similar to cell membrane, to the surfaces. “We will then expose the biomimetic surfaces to lipoprotein to understand the nature of the interaction between lipoprotein particles and the biological surfaces.”

4.

Between seven and ten per cent of the population have periodontitis or caries, for which treatments are expensive and often applied at an advanced stage. Now Biofilms Research Center for Biointerfaces at Malmö University has received SEK 4.8 million from the KK Foundation to find new methods of attacking the problem at a much earlier stage.

“The film which forms on the teeth, both above and below the gumline, is really nothing other than a dense accumulation of bacteria”, says Gunnel Svensäter, Professor of Oral Health at the Faculty of Odontology at Malmö University.

“The bacteria above the gumline, on the part of the teeth exposed to the oral cavity, cause

caries. The bacteria below the gum cause periodontitis, that is inflammation and breakdown of the gums and bone, which slowly leads to loosening of the teeth”.

Currently, visits to the dentists mainly involve mechanically removing accumulated plaque and mending holes in the teeth. Treatment of caries and periodontitis is very expensive. Gunnel Svensäter hopes that the study, planned to run for four years and expected to generate at least six or seven research articles, will lead to completely new approaches.

“The study aims to find different tools to counteract the buildup of plaque before it takes off and to combat caries and periodontitis. It is about changing the conditions for

on the hunt foR oRgAnic methods AgAinst cARies And peRiodontitis

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Annual Report 2014

How do you get a substance to penetrate the skin, a substance which can heal and do good? To get it through our barrier against the outside world, but not so far that it is transported away by the blood – enabling it to remain where its effects are needed? This is what Biofilms – Research Center for Biointerfaces at Malmö University is investigating in a new research project funded by the KK Foundation.

The outermost layer of the skin is only ten microns thick and yet it is the main barrier between the body and its surroundings. In total, skin is half a millimetre thick and its most important functions include protecting us against cold and dehydration. But sometimes, for example if we have eczema, we want the skin to absorb a pharmaceutical substance in a cream or ointment we apply to the exact spot we want to treat.

“What we are going to investigate is how to make it easier for the drug molecules to penetrate and then stay in the location where they can be useful”, explains Johan Engblom, who is a reader in Pharmaceutical Technology in charge of this research field at Biofilms – Research Center for Biointerfaces.

“The major challenge is to get the substance through the stratum corneum, the outermost layer of the skin which forms blisters when the skin is rubbed sore. It is often said that this layer accounts for approximately 80 per cent of the barrier properties. It consists of dead, flattened cells, whereas the underlying layer consists of living tissue. This is the level at which we want the substance to remain and be absorbed, rather than transported away from the site by the blood to affect the rest of the body”, says Johan Engblom.

This is precisely the advantage of allowing drugs to be absorbed through the skin: the parts of the body where the drug is not needed are not involved in the treatment through blood circulation or digestion, which limits the risk of sideeffects. The amount of active substance needed is also reduced when the drug is delivered through the skin instead of via the blood.

The project originates from research work conducted by Johan Engblom’s doctoral students and postdocs at Malmö University. The project has received SEK 4.8 million from the KK Foundation and partners are pharmaceutical companies Emeriti Pharma, Galenica

objective: to stAY just within the skin’s pRotective bARRieR

the bacteria. The bacteria which cause caries thrive in a low pH environment, i.e. an acid environment, and those which cause periodontitis do well in nutritious environments. In addition, the biofilms in which the caries and periodontitis are born have completely separate ecologies – they survive on different nutrients, have very different compositions, different physicalchemical conditions and different access to oxygen and nutrition”.

“What we want to find is an organic treatment; we will be investigating a number of substances which can change the environment for the bacteria and make it more alkaline and lean. These are the keys we are looking for”, says Gunnel Svensäter.

Naturally, it will take some time before the

market gets to see the results of the study in the form of a dietary supplement which can be taken to prevent caries and periodontitis. The study will be followed by a patenting process. The project is being carried out together with Lundbased companies Enzymatica AB and A1M Pharma. There are plans for both laboratory experiments and a clinical pilot study. “We have already worked together with Enzymatica and can see that both they and A1M Pharma are very well suited to our activities – they maintain a high academic standard and have a solid basis in our world”, says Gunnel Svensäter.

In addition to the project manager Gunnel Svensäter, the participants from Malmö University are Julia Davies, Claes Wickström, Mikael Sonesson and Jessica Neilands.

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Annual Report 2014

AB and Bioglan AB. Gothenburg University is also in the group behind the application.

In fact the pharmaceutical substances involved are of secondary importance; the object of the investigation is how molecules with different chemical properties can more easily get to where they are needed.

“We have chosen a fatsoluble and a watersoluble model substance. These molecules can go different ways – it’s quite possible that a larger door will be opened for the watersoluble molecule than for the fatsoluble one, or vice versa. Most pharmaceutical molecules have oil properties, i.e. they are fatsoluble, whereas most creams are watersoluble.

Oil and water don’t mix. This is central to much of what we do here at the research centre. To simplify somewhat, creams are usually drops of oil in water, together with an emulsifier which makes the consistency smooth. But water drops in oil make the cream more like an ointment. Ointments are stickier and not as manageable as creams. There is more demand for creams. Gels consist largely of water which evaporates on application to the skin. Ointment, cream or gel – often a

company can choose to produce a variant of each with the same pharmaceutical substance, in order to cover a larger market segment. We are working with all three variants, but creams are the most common”.

Johan Engblom observes that the research network which is now being established in southern Sweden is strong and competitive, and will connect chemistry and medicine more closely. The project has been underway since March and will run for three years. From Malmö University, the participants are Johan Engblom, Tautgirdas Ruzgas, Peter Falkman, Cathrine Albèr and a new postdoc. Further participants are Henri Hansson and Anna Karin Morén from Galenica, Birgitta Svensson and Torbjörn Sund from Bioglan, David Gustafsson and Tomas Fex from Emeriti Pharma, and Marica Ericson from Gothenburg University. The project is expected to generate at least six research publications.

“We have a formalised timetable, but as with all scientific studies, new issues are bound to arise along the way and the lessons we learn from them will obviously affect the paths we choose in the project”, says Johan Engblom.

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Annual Report 2014

wORkSHOpS AND CONFERENCES ORgANISED BY THE CENTER

The Center held the 10th Annual Work

shop in October. The focus this year was

Nanomedicine and the event attracted

more than 90 participants from different

universities as well as industry. Read more

about the workshop in the article below.

The 15th International Conference on

Electroanalysis was held at Malmö

University on June 11–15, 2014. These

biannual conferences have become

recognised worldwide as distinguished

electroanalytical meetings within the

framework of the European Society for

Electroanalytical Chemistry. The confer

ence covered virtually every aspect of

modern as well as classical electroanalysis,

ranging from theoretical approaches to

practical applications in different fields.

The conference attracted around 230

participants from all over the world and

was organised by Malmö University in

collaboration with Uppsala University,

the Technical University of Denmark

and Lund University. Tautgirdas Ruz

gas, Thomas Arnebrant and Sergey

Shleev were members of the organizing

committee.

http://eseac2014.com/

Börje Sellergren, who is coordinating

the EU FP7 Marie Curie Initial Training

Network PEPMIP – Robust affinity mate

rials for applications in proteomics and

diagnostics, organised the Lipidomics,

Proteomics and related technologies work

shop at Malmö University in November.

Also worth mentioning is the interview with Sergey Shleev in the TV programme TV4 Nyheterna:http://www.tv4.se/nyheterna/klipp/ny-k%C3%A4lla-f%C3%B6r-elektrisk-energi-presenteras-p%C3%A5-konferens-i-malm%C3%B6-2658757

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Annual Report 2014

Each year, Biofilms – Research Centre for Biointerfaces holds a workshop aimed at researchers, industry and other stakeholders in life science and biomedicine. This year’s theme was nanomedicine – the use of nanotechnology in medical applications.

nAnomedicine in focus At AnnuAl woRkshop

Ulrik B Nielsen is CSO at Merrimack

Pharmaceuticals in Boston and one of the

founders of the company: “It has been

a very interesting workshop and with

excellent speakers. This is the first time

I’ve attended and I realise exactly how

valuable this workshop is for those of us

who work in the industry.”

Applications in diagnostics and treatment

The workshop was held for the first time at

Medeon, which is located beside the new

premises of Biofilms – Research Centre for

Biointerfaces and offered a whole range

of lectures and presentations in the field

of nanomedicine.

“Nanomedicine is about how nanotech

nology can be used for different medical

applications in order to diagnose or treat

patients. It is naturally extremely pleasing

to see such interest in the workshop and

that we have so many thought provoking

speakers,” said Anna Holmberg, Director

of Biofilms – Research Centre for Bio

interfaces.

pROMINENT SpEAkERS

During the workshop, prominent speakers

and representatives from industry spoke

on a variety of subjects, including how

different types of nanostructures and

nanoparticles can be used for implants

and drug delivery – across the skin, for

example.

“It is an extremely exciting programme

and a number of the presentations will

be of direct benefit to me in my work

on drug delivery,” said Louise Bastholm

Jensen from Leo Pharma.

MEASURINg SIgNALS IN THE BRAIN

Ulrik B Nielsen, Merrimack Pharma

ceuticals, spoke about his work with dif

ferent cancer therapies. The company has

several new treatments that will shortly

be brought to market. Professor Jens

Schouenborg from Lund University spoke

about the design of implantable electronic

interfaces for the brain. The aim is to be

able to connect the brain to a computer.

NANOSTRUCTURES

OFFER BETTER IMpLANTS

Representatives from Malmö University

included Professor Ann Wennberg, who

spoke about how nanostructures can

improve osseointegration. Professor

Tautgirdas Ruzgas spoke about a new

method for studying the absorption of

substances, such as drugs, across the skin.

“The presentations were incredibly

inspiring and are strongly linked to our

studies. I have acquired many new

ideas,” said Sviram Thoppe Rajendra, a

Master’s student at Biomedical Methods

and Technology, who was supported in

his view by fellow programme member

Linn Stenfelt.

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Annual Report 2014

Different physicochemical properties (e.g. adsorption kinetics, thickness, viscoelasticity, mechanical stability, etc.) of adsorbed salivary pellicles depend on different factors including the properties (charge, roughness, wettability, surface chemistry, etc.) of the substratum. Whether these differences in physicochemical properties are a result of differences in the composition or in the organization of the pellicles is unknown. We have approached this by investigating pellicles eluted from substrata of different but wellcharacterized wettabilities by means of SDSPAGE. The resulting gels have been analyzed by various staining technique as well as immunoblotting procedures [1].

Whereas some compositional differences were observed, the stained SDSPAGE gels reveal a similar compositional pattern for the pellicles harvested from substrates of different wettability. In CBB stained gels (Fig. 1a), the more intense bands, i.e. those corresponding to MWs of ≈ 190 kDa, 56-59 kDa and 18 kDa, were found for all the investigated pellicles. Blotting experiments (Fig. 1b) suggested that the double band observed between 56-59 kDa could be attributed to amylases, specifically to the nonglycosylated and glycosylated isoforms. Blotting experiments also attributed the band observed at ≈ 18 kDa to cystatins. PAS stained SDSPAGE gels (Fig. 1c) of all the eluted samples demonstrated positive

glycoprotein bands at high MW (> 400 kDa, close to the wells of gels) and at a MW of ≈ 180 kDa. It is reasonable to attribute the high MW band to MUC5B and the 180 kDa band to MUC7.

Thus, our results showed that substratum hydrophobicity did not have a major impact on pellicle composition. In all substrata, the major pellicle components were found to be cystatins, amylases and large glycoproteins, presumably mucins. It is enlightening to discuss our results in terms of the wellaccepted twolayer model for salivary pellicles. This model states that, on most types of substrate, pellicles consist of an inner thin dense layer (which would be formed mainly by proteins of relatively low MW) and an outer thick diffuse layer (mainly composed of mucins). Our results showing the presence of mucins in all pellicles support their presence in the outer layer. Cystatins and amylases (in this order), will diffuse to the substrate faster than mucins because of having a lower MW being, therefore, the major components of the inner dense layer. In this scheme, substrate wettability will mainly affect the nature and magnitude of the forces driving the adsorption of the components of the inner layer and, subsequently, their orientation. In [1] it is discussed how this simple scheme would account for most of the physicochemical properties reported for salivary pellicles.

RESEARCH HIgHLIgHTS

influence of substRAtum hYdRophobicitY on sAlivARY pellicles: oRgAnizAtion oR composition?

[1] Aroonsang W., Sotres J., ElSchich Z., Arnebrant T., Lindh L. 2014. Influence of substratum hydrophobicity on salivary pellicles: organization or composition? Biofouling, 30: 1123-1132.

contact: [email protected]

1.

figure 1. a) Representative CBB-250-stained SDS-pAgE gels of pellicles harvested from substrates characterized by different water contact angles, . b) Representative illustration of immunoblots of the same pellicles as in a) probed with antibodies against amylase and cystatin-S. c) Representative pAS-stained SDS-pAgE gels of the same pellicles as in a). figure 2. Simplified scheme proposed for salivary pellicles.

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Annual Report 2014

selection of multispecies heAlth-AssociAted biofilms using sAlivA As A nutRient souRceOral microbial biofilms support host defences by preventing colonization by exogenous pathogenic microbes. The integrity of mucosal surfaces relies, in part, on the ability of the hostderived mucus layer to aid colonization of commensal bacterial biofilms. In oral microbial biofilms (supragingival dental plaque) salivary proteins serve as a major ecological determinant of the composition of the microbial community, enables adhesion and growth, and are the major continuously available source of nutrients. To yield nutri

ents, the degradation of complex substrates, including salivary mucins, requires an arsenal of glycosidases and proteases. Several bacterial species, which possess complementary patterns of glycosidases and proteases, catabolize glycoproteins through a concerted action. In order to study how saliva and the oral bacterial community interact and how this interaction influences the composition and phenotype of the oral biofilm, supragingival plaque was grown in bacteria free human whole saliva as described below.


Supragingival plaque samples were taken from healthy subjects and grown in 50% saliva for up to 7 days in 5% CO2. The microbial composition and enzymatic profile was determined after 0-, 2-, 5- and 7 days of growth. Similar changes in the microbial biofilms and enzymatic profiles were seen in three experiments. In all experiments, the enzymatic activity of galactosidase, galactosaminidase and glucosaminidase was increased and the enzymatic activity of glucosidase decreased

over 7 days. The sialidase and fucosidase activity remained the same. At the same time the protease activity increased. Hence, the enzyme profile of the biofilm changes due to the altered nutritional environment. This also indicates that the bacteria degrades and uses salivary mucins and proteins as nutrients. The saliva environment also seemed to select the growth of Actinomyces species and Capnocytophaga species.

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Annual Report 2014

Mucins represent the major macromolecule comprising the mucus gels or glycalyx on the epithelial cell membranes. Biological functions of mucus gels are known to range from the protection of underlying tissues against external insult, mechanical stress, and pathogens to cell signal transduction. Inspired from their protective biological functions, mucins started to attract interest as coating materials for implants and biomedical devices.

We have investigated the mechanical stability of adsorbed mucin films (specifically bovine submaxillary mucin films) by means of an atomic force microscope operated in the friction force spectroscopy mode [1]. This methodology provides the strength of the adsorbed films in terms of the forces needed for breaking and removing them. More specifically, we have investigated how this stability depend on the pH of the ambient medium and on the wettability of the substrate. Our results showed that, for all studied pHs, mucin films formed on hydrophobic substrates are significantly stronger than those formed on hydrophilic substrates. Moreover, mucin films, formed on both hydrophobic and hydrophilic substrates, probed at acidic conditions are significantly stronger than those probed at neutral pH conditions.

These results have important implications not only for the understanding of the mechanical behavior of mucus gels and artificial mucin coatings, but for the understanding of salivary lubrication mechanism as well. Saliva has attracted an increasing interest as a waterbased biological lubricant due to its unique property of lubricating almost any type of surface. Salivary lubrication is attributed to the film of nanometric dimensions that forms immediately upon contact of saliva with any type of surface, i.e. the acquired pellicle. Mucins are one of the pellicle components shown to have a major impact of the friction reduction properties of the pellicle [2]. But a good lubricant not only reduces friction but must resist wear as well. A comparison (Fig. 1) between our results on the mechanical stability of mucins with those previously obtained on salivary films [2] reveals that, on hydrophilic substrates, saliva forms significantly stronger films than mucins do. This relationship also holds for films formed on hydrophobic substrates at neutral pH, while mucin films are stronger than salivary ones when formed on hydrophobic substrates at acidic conditions. Therefore, it is obvious that salivary lubrication, i.e. its ability to reduce friction and wear, results from the synergistic action of several of its components.

[1] Sotres J., Madsen J.B., Arnebrant T., Lee S. 2014. Adsorption and nanowear properties of bovine submaxillary mucin films on solid surfaces: Influence of solution pH and substrate hydrophobicity. J. Colloid Interface Sci. 428: 242-250.[2] Lindh L., Aroonsang W., Sotres J., Arnebrant T. 2014. Salivary Pellicles in Saliva, Monographs in Oral Science, 24: 30-39.


mechAnicAl stAbilitY of mucin films: implicAtions on sAlivARY lubRicAtion

3.

figure 1. Load forces needed to completely remove salivary and mucin (BSM) films. Comparisons are shown for films formed on model hydrophilic and hydrophobic substrates, and for neutral and acidic pH conditions.

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Annual Report 2014

4.

Periimplantitis is a biofilminduced destructive inflammatory process that, over time, results in loss of supporting bone around an osseointegrated dental implant. Inflammation is accompanied by an increased tissue proteolysis instrumental in driving bone destruction. Bacterial biofilms at periimplantitis sites have been reported to be dominated by Gramnegative anaerobic rods such as Fusobacterium, Porphyromonas, Prevotella and Tannerella with a proteolytic metabolism, as well as anaerobic streptococci. The hypothesis of this study was that a high pro-tease activity would be detected in samples of periimplant fluid from periimplantitis patients.

The microbial composition and level of protease activity in samples of periimplant biofluid from 25 implant patients with healthy support tissues and 25 patients with periimplantitis were compared. Microbial composition was studied using culture techniques and protease activity was determined using FITClabeled casein.

There was a pronounced interindividual variation in the microbial composition in both groups. Fusobacterium, Porphyromonas, Prevotella and Tannerella, anaerobic genera that all have been implicated in periimplant

disease, were found in both groups. However, the prevalence of Porphyromonas/Prevotella was significantly higher in the periimplantitis group than in the unaffected group. The most striking finding was that strictly anaerobic streptococci were almost exclusively found in the periimplantitis group (Fig 1)

The mean protease activity in the periimplant biofluid was about twice as high in the periimplantitis group as in the healthy group. The level of protease activity could not be correlated to the presence of any specific bacterial species. Instead, we propose that the presence of proteolytic bacterial phenotypes and high levels of protease activity in the periimplant biofluids may be a predictive factor for disease progression in periimplantitis. Further longitudinal studies are however required to determine whether assessment of protease activity could serve as a useful complement to other methods to identify patients at risk of progressive tissue destruction.

peRiimplAntitis, bActeRiAl species And pRoteolYtic phenotYpes

Project partners: J. Neilands, C. Wickström, B. Kinnby, J. R. Davies, J. Hall, B. Friberg and G. Svensäter

contact: gunnel.svensä[email protected]

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Annual Report 2014

plAsminogen ActivAtoR inhibitoR tYpe 2 inhibits pRoteolYtic ActivitY of A multi-species bActeRiAl consoRtium

The plasminogen activator inhibitor PAI2 (SerpinB2) has been called the most enigmatic serine protease inhibitor (serpin) because it lacks an obvious endogenous target protease. Among cells producing PAI2 are macrophages and keratinocytes in skin and mucosa. PAI2 is rapidly induced by LPS. Thus, PAI2 may have evolved as a part of the defense against bacteria. The highest level of PAI2 has been found in the gingiva, an area characterized by the presence of a resident microflora that is important for oral health. An increased accumulation of bacteria leads to an inflammatory response, resulting in an increased flow of gingival fluid initiating an ecological shift. The results is an increased nutrient supply for bacteria dependent on peptides as their source of energy. In addition to degrading proteins for growth, bacterial proteases act as virulence factors, causing tissue damage and modulation of the host defense. No previous studies have demonstrated inhibition of bacterial proteases by PAI2. The aim of the present study was therefore to study possible interactions between PAI2 and proteases produced by bacteria in a multi species consortium resembling the resident microflora at subgingival sites.

A ninespecies bacterial consortium characteristic of periodontal pathology was grown for 7 days until a high proteolytic activity was expressed. The proteolytic activity of the culture supernatants was assayed using FITClabeled casein and that of the biofilm bacteria by confocal microscopy using fluorescent substrates. We found that PAI2 readily inhibits proteolytic activity in the supernatants from these bacteria (Fig 1) as well as surfaceassociated protease activity (Fig 2). This supports the hypothesis that PAI2 is present in epithelium as a defense barrier against proteaseproducing bacteria. This may be a future approach to treatment of destructive periodontal inflammation.

5.

Project partners: J. Neilands and B. Kinnby


figure 2. protease activity visualized through blue fluorescence.

control +pai-2

figure 1.

17


Annual Report 2014

Plasminogen is a major plasma protein and the zymogen of the broad spectrum protease plasmin. Plasmin activity leads to tissue degradation, both directly and indirectly through activation of metalloproteinases. Infected tooth root canals, as a consequence of the inflammatory response and eventual necrosis, contain tissue fluid and blood components. These will coat the root canal walls and act as conditioning films that allow bacterial biofilms to grow and be a potential source for hematogenic spread of bacteria.

We investigated the effect of in vitro surface conditioning with human plasminogen on the initial adhesion of bacteria. Four bacterial species, L. salivarius, E. faecalis, A. naeslundii, and S. gordonii, isolated from dental root canals, and three other oral streptococci (S. anginosus, S. oralis, and S. sanguinis) were grown in albumin or plasminogencoated flow chambers and studied by confocal laser scanning microscopy using the cell viability staining LIVE/DEAD and 16S rRNA fluorescence in situ hybridization (FISH).

A. naeslundii, L. salivarius and in particular S. gordonii showed a higher initial adhesion to the plasminogencoated surfaces. E. faecalis did not show any preference for plasminogen (Fig 1). Fourspecies biofilms cultured for 96h showed that streptococci increased in proportion with time (Fig 2). Further experiments aimed at studying different streptococcal strains. All these adhered more to plasminogencoated surfaces than to albumincoated control surfaces (Fig 3). Plasminogen is thus an important plasma component for the initial adhesion of oral bacteria, in particular streptococci. This binding may contribute to their spread locally as well as to distant organs or tissues.

plAsminogen coAting incReAses initiAl Adhesion of oRAl bActeRiA to in vitRo suRfAces

6.

Project partners: B. Kinnby and L. E. Chávez de Paz


figure 1.

figure 3.

figure 2.

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Annual Report 2014

AmpeRometRic monitoRing of dRug penetRAtion thRough skin

7.

Transdermal drug delivery represents an attractive alternative to oral delivery especially when poor drug absorption or enzymatic degradation in the gastrointestinal tract or liver is a problem. From the first transdermal patch for treating motion sickness approved by the FDA in 1979, to the most recently approved patch for migraine (Sumatriptan), a total of more than 20 drugs with transdermal delivery have been commercialized so far.

The progress in developing transdermal drug delivery devices and methods to a great extend depends on the understanding properties of stratum corneum (SC). Stratum corneum (SC), the outermost thin layer of the skin, represents the major resistance to transdermal drug delivery. Characterizing the electrical properties of the skin in combination with penetration investigations can help the evaluation of the drug transport mechanisms across skin [1]. Penetration of compounds through SC or whole skin membranes is often studied by

exploiting flow through diffusion cells or Franz cells. However, dynamics of penetration is difficult to study using Franz cell based method. At the department of Biomedical Sciences we have developed amperomentric invitro methods for monitoring penetration of biologically active compounds through skin membranes, Fig. 1. Skin membrane is fixed on the top of chemically modified electrode and penetration of the appropriate compound is registered as electrode current. By using this method penetration dynamics of biologically active compounds possessing very different properties has been studied. Specifically, the electrochemical method was elaborated to monitor dynamics of penetration of quercetin, hydrogen peroxide and ascorbic acid. The methodology allows the study of penetration from solution as well as from pharmaceutical creams. From realtime measurements of electrode current, fluxes and diffusion coefficients of mentioned compounds in skin membranes have been estimated [2].

figure 1. (Left) photos of skin membranes-covered electrodes and schematic presentation of the electrode construction. (Right) Dynamics of penetration of different compounds through skin membrane recorded as alectrode current vs time dependencies. The penetration of quercetin and ascorbic acid was studied from soluti on, hydrogen peroxide from 1% containing peroxide cream.

[1] S. Björklund, T. Ruzgas, A. Nowacka, I. Dahi, D. Topgaard, E. Sparr, and J. Engblom. Skin membrane electrical impedance properties under the influence of a varying water gradient. Biophys. J. (2013), 104, 2639-2650.

[2] H. Gari, J. Rembiesa, I. Masilionis, N. Vreva, B. Svensson, T. Sund, H. Hansson, A. K. Morén, M. Sjöö, M. Wahlgren, J. Engblom, and T. Ruzgas. Amperometric In Vitro Monitoring of Penetration through Skin Membrane. Electroanalysis, (2015), 27, 111 – 117.


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Annual Report 2014

Humectants belong to a group of hydrophilic compounds frequently used in skin care products with the aim to diminish the clinical symptoms of skin dryness. The biochemical and biophysical mechanisms by which humectants interact with the skin barrier are far from fully understood. Increased understanding of such mechanisms can enhance the possibilities to tailor skin care products for various skin abnormalities.

We have focused on two low molecular weight humectants (glycerol and urea) and their interactions with water, as well as their effects on the barrier properties of the outermost layer of the skin, stratum corneum (SC). Addition of urea, glycerol or PEG1500 to aqueous formulations inevitably lowers the water activity of the formulation, which in turn affects the SC permeability when these formulations are applied on the skin. In contrast to low molecular weight humectants, like urea and glycerol, it was concluded that PEG1500 does not penetrate the skin barrier

due to size exclusion [1]. Moreover, it was shown that skin permeability of the model drug metronidazole decreases upon addition of PEG1500 to the formulation, while high skin permeability was maintained with addition of urea or glycerol despite a lower water activity of these formulations [2].

Confocal Raman microspectroscopy revealed formation of large water inclusions in fully hydrated SC after 24 h exposure to a pure buffer solution. Addition of urea was shown to promote the formation of these inclusions, while no inclusions could be detected in presence of PEG1500 (i.e. in less hydrated skin) [3]. A similar approach as used in vitro was employed in vivo to explore the effect of hydration and humectants on skin permeability. It was shown that the water activity of the applied formulation has a marked effect on the barrier properties and that urea and glycerol have the ability to improve skin hydration even at reduced water activity of the applied formulation [4].

effects of wAteR ActivitY And low moleculAR weight humectAnts on skin peRmeAbilitY And hYdRAtion dYnAmics

8.

[1] Björklund S, Engblom J, Thuresson K and Sparr E, A water gradient can be used to regulate drug transport across skin, J Control Release, 143: 2, (2010) 191-200

[2] Björklund S, Engblom J, Thuresson K and Sparr E, Glycerol and urea can be used to increase skin permeability in reduced hydration conditions, Eur J Pharm Sci, 50 (2013) 638–645

[3] Albèr C, Brandner BD, Björklund S, Billsten P, Corkery RW and Engblom J. Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy. Biochimica et Biophysica Acta 1828 (2013) 2470–2478.

[4] Albèr C, BuraczewskaNorin I, Kocherbitov V, Saleem S, Lodén M and Engblom J. Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics – a doubleblind, randomized and controlled study. International Journal of Cosmetic Science 36 (2014), 412-418.


20


Annual Report 2014

Mass spectrometry (MS) methods are in high demand in the field of clinical proteomics providing sensitive, reproducible and specific biomarker quantification. They represent the highthroughput option in clinical analysis limiting the false positive rate and enhancing the specificity of diagnostic assays. Such precise quantification tools need to be selective to analyze complex clinical samples where occurrence of high abundant protein and low biomarker expression limits the dynamic range. Improvements have been achieved by adopting highresolution MS and new strategies in sample cleanup such as immuno extraction techniques. Immunoaffinity coupled with MS has been demonstrated to be highly effective in biomarker determination.

In spite of the efficiency of immunobased methods, the generation of high quality antibodies is costly and timeconsuming which commonly hampers the development of analytical methods for clinical routine diagnosis. Indeed, methods which entirely avoid the use of antibodies are of growing importance in the bioanalysis field.

An alternative approach intended to mimic antibody specificity is represented by Molecularly Imprinted Polymers (MIP), commonly referred to as plastic antibodies. These artificial receptors, with affinity recognition sites able to recognize target molecules by a lock and key mechanism, have been used extensively as sample preparation tools in small molecule analysis. This contrasts with the few reports describing assays or enrichment of biomacromolecular targets. This can be ascribed to added complexity in generating the corresponding receptors in terms of template stability and scarcity, conformational matching and mass transfer limitations. In order to demonstrate and compare these two affinitybased enrichment techniques in massspectrometry based assays, we have here focused on assays for Pro Gastrin Releasing Peptide (ProGRP), a well established biomarker for the highly metastatic cancers form, small cell lung cancer (SCLC). Early detection is crucial for positive treatment outcomes and new diagnostic modalities for SCLC biomarker determination assume absolute importance.

AntibodY-fRee biomARkeR deteRminAtion: exploRing moleculARlY impRinted polYmeRs foR pRo-gAstRin ReleAsing peptide

9.

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Annual Report 2014

[1] Qader, A. A.; Urraca, J.; Torsetnes, S. B.; Tönnesen, F.; Reubsaet, L.; Sellergren, B. Peptide imprinted receptors for the determination of the small cell lung cancer associated biomarker progastrin releasing peptide. J. Chromatogr. A. 2014, 1370, 56-62.

[2] Rossetti, C.; Qader, A. A.; Halvorsen, T. G.; Sellergren, B.; Reubsaet, L. Antibodyfree biomarker determination : exploring molecularly imprinted polymers for progastrin releasing Peptide. Anal. Chem. 2014, 86, 12291–12298


Absolute quantification of ProGRP by MS was formerly investigated by the means of its signature peptide, NLLGLIEAK, a unique proteotypic nonapeptide detectable with high signal intensity. The aim of this work was to develop an alternative enrichment strategy in targeted proteomics exploring MIP based peptide capture. In contrast to MIPs targeting proteins the imprinting of peptides obviates the need for labile and expensive proteinaceous templates and is compatible with a wide range of solvents, monomers and elevated temperatures. Apart from synthetic ease this approach moreover allows a direct comparison with the increasingly popular methods relying on immunobased peptide capture. We have identified polymers prepared using the hydrophobic crosslinker divinilbenzene (DVB) and the functional monomer N(2aminoethyl) methacrylamide hydrochloride (EAMA) imprinted with N and C protected forms of the

signature peptide of ProGRP (NLLGLIEAK) to display particularly promising recognition properties [1]. Polymers prepared using this combination exhibited significant imprinting, yielding higher peptide recovery in the MIP extract when compared with the respective nonimprinted polymer. With this as starting point we have here developed novel peptide imprinted thin film composite beads and used them in conjunction with tandem mass spectrometry (MS/MS) in the bottomup workflow for absolute quantification [2]. A selectivity study was performed by evaluating both imprinted and nonimprinted polymers with respect to retention behavior of the target peptide (NLLGLIEAK) and other, nontarget, peptides. Ultimately the MIP’s potential in analysis of biological samples was demonstrated with respect to affinity and selectivity by applying the developed protocol to ProGRP fortified serum sample.

22


Annual Report 2014

The critical advances in the fuel cell and capacitors technologies enabled the development of a new kind of devices, hybrid electric power devices, viz. selfcharging supercapacitors or, in other words, chargestoring fuel cells. Scientifically a dualfunction electrode, viz. a discrete electrode concurrently manifesting electrocatalytic and chargestorage features, is disclosed.

Hybrid electric power device is a combination of an electrochemical capacitor and a fuel cell in a singular indivisible module. To create efficient devices, which can be miniaturised

even down to the nm scale and used for shorttime highcurrent and longtime lowcurrent practical applications, both elements (capacitive and electrocatalytic) were built from nano(bio)composite materials. Energy storing parts were built from the conducting organic polymer (e.g. polyaniline (PANI), polypyrrole (PPy))/carbon nanotube (CNT) nanocomposites immobilised on the surface of gold or graphite electrodes. Energy generating parts of hybrid electric power devices were based on nonbiological (organic (PANI) or inorganic (platinum (Pt)) or biological (redox enzymes) catalysts (see figure below) [1].

hYbRid electRic poweR devices foR simultAneous geneRAtion And stoRAge of electRic poweR

The work has been supported financially

by the Swedish Research Council (2013-

6006) and by the Russian Foundation for

Basic Research (13-04-12083 ofi_m).

[1] Pankratov, D., Blum, Z., Shleev, S. Hybrid electric power biodevices. ChemElectroChem. 2014, 1, 1798-1807.

[2] D. Pankratov, Z. Blum, D. Suyatin, V. Popov, S. Shleev. Selfcharging electrochemical biocapacitor, ChemElectroChem 2014, 2, 343-346.

[3] D. Pankratov, P. Falkman, Z. Blum, S. Shleev. A hybrid electric power device for simultaneous generation and storage of electric energy. Energy Environ. Sci. 2014, 7, 989-993.


(Left) Self-charging biosupercapacior, (Right) Charge-storing fuel cell.

Operating in a pulsed power mode, hybrid electric power device s based on biological [2] and nonbiological [3] catalysts provided a maximum power density of 1.2 mW cm –2 and 1.4 mW cm –2 at 0.38 V, respectively. Thus, the power output was improved by a factor of around 100 in comparison to fuel cells based on the same catalysts.

Several niches for practical applications of these new devices can be envisaged, depending on the fuels and oxidants used. Hybrid electric power devices are able to act as supercapacitors, efficiently amassing large amounts of electric energy in a short time, and concurrently act as fuel cells, continuously supplying electric power, converted directly from chemical energy.

10.

23


Annual Report 2014

Degradable starch microspheres are used for drug delivery and also as a medical device for acceleration of wound healing by promoting hemostasis. In both applications hydrationdependent properties are essential for effective functioning of the microspheres. In a KKfunded project “Carbohydrate polymer – water interactions: sorption, porosity and rheology” we study effects of hydration on properties of starch microspheres and other carbohydrate systems.

In particular we investigated effects of crosslinks on properties of starch microparticles. Isothermal sorption calorimetry showed that crosslinks prevent crystallization of starch, which follows from the absence of crystallization peak, see figure below. The

isothermal glass transition is clearly seen in both materials, crosslinking shifts it to higher water contents. The absence of crystallization improves hygroscopicity of the particles, which is important for application as a medical device. The crystallization of acidhydrolyzed starch in the absence of crosslinks produces different crystalline structures depending on hydration levels, as is evident from synchrotron radiation Xray data obtained at MAXLAB. The Xray data treated using concept of fractals, also provided information on evolution of the microparticle surface and polymer chain properties as function of hydration. Based on results from several experimental methods we constructed temperaturecomposition phase diagrams of several starch materials.

hYdRAtion induced phenomenA in stARch micRopARticles

Carlstedt, J., Wojtasz, J., Fyhr, P., Kocherbitov, V. (2014) Hydration and the phase diagram of acid hydrolyzed potato starch. Carbohydrate Polymers, 112, 569–577

Wojtasz, J., Carlstedt, J., Fyhr, P., Kocherbitov, V. Hydration and swelling of amorphous crosslinked starch microspheres. Submitteda


SEM: starch microspheres (dried) Sorption calorimetry: black curve – starch microspheres, red curve – acid hydrolyzed starch

11.

24


Annual Report 2014

Polyether ether ketone (PEEK) is today frequently used as a biomaterial in different medical operations due to its excellent mechanical and chemical properties. However, the untreated surface of PEEK is bioinert, hydrophobic and does not osseointegrate in its pure form. The aim of this study was to evaluate a nano CaP coated PEEK with

respect to enhanced osseointegration. The control implants were uncoated PEEK screws. Evaluation of material characteristics and evaluation of removal torque as a measure of osseointegration were performed. The results demonstrated a CaP coating did not influence the mechanical properties of PEEK but did enhance the osseointegration.

biomechAnicAl evAluAtion And suRfAce chARActeRizAtion of A nAno-modified suRfAce on peek implAnts: A studY in the RAbbit tibiA

Mean values and standard deviation of removal torque (Ncm) at both healing periods.

Histological section of one deceased rabbit after 3 weeks of healing

Johansson P., Jimbo R., Kjellin P., Currie F., Chrcanovic B., Wennerberg A.Johansson, Biomechanical evaluation and surface characterization of a nanomodified surface on PEEK implants: a study in the rabbit tibia, Int J Nanomedicine. 2014 Aug 14;9:3903-11


12.

SEM images of coated pEEk at 80k magnification (A) and 10k magnification (B) and uncoated pEEk at 80k magnification (C) and 10k magnification (D)

A B

C D

25


Annual Report 2014

osteoconductive potentiAl of mesopoRous titAniA implAnt suRfAces loAded with mAg-nesium: An expeRimentAl studY in the RAbbit

background and aim: Mesoporous coatings enable incorporation of functional substances and sustainedly release them at the implant site. One bioactive substance that can be incorporated in mesoporous is magnesium, which is strongly involved in

bone metabolism and in osteoblast interaction. The aim of this project was to evaluate the effect of incorporation of magnesium into mesoporous coatings of oral implants on osseointegration.results of the animal study:

Published articles related to this project:

[1] Local release of magnesium from mesoporous TiO2 coatings stimulates the periimplant expression of osteogenic markers and improves osteoconductivity in vivo., Galli S, Naito Y, Karlsson J, He W, Miyamoto I, Xue Y, Andersson M, Mustafa K, Wennerberg A, Jimbo R. Acta Biomater. 2014 Dec;10(12):5193-201.

[2] Osteoconductive Potential of Mesoporous Titania Implant Surfaces Loaded with Magnesium: An Experimental Study in the Rabbit., Galli S, Naito Y, Karlsson J, He W, Andersson M, Wennerberg A, Jimbo R., Clin Implant Dent Relat Res. 2014

contact: [email protected], [email protected]

conclusion and future perspectives: It can be said that the effect of magnesium is significant to bone regeneration when appropriate carriers are selected. The results of the current project show that the magnesium enhanced osseointegration. The mechanisms

of the influence of magnesium and its longer effects needs to be investigated in future studies, however, the magnesium releasing biomaterial have the potential to improve the bone integrating medical devices.

13.

figure 1. Removal Torque testing (RTq) showed that the mesoporous coated implants loaded with magnesium presented significantly higher biomechanical bonding to the bone in a rabbit tibia model.

figure 2. Descriptive histological image of bone healing around a mesoporous implant loaded with magnesium. Active bone modeling and remodeling can be observed at the bone-implant interface.

figure 3. The real time RT-qpCR displayed the relative quantification of the expression of the panel of gene assays selected. There was a significant genetic effect of the mag-nesium loaded mesoporous implants. The significantly expressed bone modeling, remodeling related genes are noted with asterisks.

26


Annual Report 2014

LIST OF CENTER MEMBERS

1. mAnAgement And boARdssteeRing committee

Cristina Glad

Chair

CEO C glad Consulting AB

Thomas Arnebrant

Representative Faculty of Health and Society

Gunnel Svensäter

Representative Faculty of Odontology

Karl Obrant

Head of Research, Skåne university Hospital

Markus Johnsson

Senior Director, pharmaceutical

Development, Camurus AB

Ulf Brogren

CEO promimic AB

Peter Nordström

Senior project Manager, Medicon valley

Alliance

senioR ReseARcheRs foRum

Anna Holmberg

Chair

phD, Director

Alexei Iantchenko

professor

Ann Wennerberg

professor

Börje Sellergren

professor

Gunnel Svensäter

professor

Julia Davies

professor

Liselott Lindh

professor

Per Jönsson

professor

Sergey Shleev

professor

Tautgirdas Ruzgas

professor

Thomas Arnebrant

professor

Anette GjörloffWingren

Assoc. professor

Bertil Kinnby

Assoc. professor

During 2014, the Center comprised the following members.

2.

27


Annual Report 2014

peRmAnent AcAdemic stAff

Anna Holmberg, phD, Director

Alexei Iantchenko, professor

Ann Wennerberg, professor

Börje Sellergren, professor

Gunnel Svensäter, professor

Håkan Eriksson, professor

Julia Davies, professor

Lennart Ljunggren, professor

Liselott Lindh, professor

Per Jönsson, professor

Sergey Shleev, professor

Tautgirdas Ruzgas, professor

Thomas Arnebrant, professor

Anette GjörloffWingren, Assoc. professor

Bertil Kinnby, Assoc. professor

Christina Bjerkén, Assoc. professor

Claes Wickström, Assoc. professor

Krister Thuresson, Assoc. professor

(external)

Johan Engblom, Assoc. professor

Marité Cárdenas Gómez, Assoc. professor

Petri Gudmundsson, Assoc. professor

Ryo Jimbo, Assoc. professor

Vitaly Kocherbitov, Assoc. professor

Zoltan Blum, Assoc. professor

Gabriela Enggren, phD

Jakob Blomqvist, phD

Javier Sotres, phD

Jessica Neilands, phD

Lars Ohlsson, phD

Maria Stollenwerk, phD

Tove Sandberg, phD

Ravi Danielsson, phD

Yuanji Cheng, phD

3.

Christina Bjerkén

Assoc. professor

Claes Wickström

Assoc. professor

Johan Engblom

Assoc. professor

Vitaly Kocherbitov

Assoc. professor

Gabriela Enggren

phD

Maria Stollenwerk

phD

28


Annual Report 2014

technicAl And AdministRAtive stAff

Eva Nilsson, Administrative coordinator

Agnethe Henriksson, Technician

Madeleine Blomqvist, Technician

Ulrika Troedsson, phD, Technician

Peter Falkman, phD, Research engineer

phd students

Ali Alenezi

Anton Fagerström

Bruno Chrcanovic

Cathrine Albér

Celina Wierzbicka

Deyar Mahmood

Dmitrii Pankratov

Adjunct fAcultY

Justas Barauskas, phD

Senior scientist, Camurus AB

Tobias Halthur, phD

project Manager, CR Competence AB

4.

5.

junioR ReseARcheRs And post-docs

Anna Runnsjö, phD

Hala Ghandour Gari, phD

Jildiz Hamit Eminovski, phD

Jonas Carlstedt, phD

Grzegorz Lisak, phD from Åbo Akademi university, Finland (guest for one year)

Maria Falck Miniotis, phD

Pär Olsson, phD

Soma Ghosh, phD

Sudhirkumar Shinde, phD

Sebastian Björklund, phD

6.

Francesca Cecchinato

Jonas Anderud

Elena Gonzalez

Magnus Falk

Mariko Hayashi

Marjan Dorkhan

Mark Galat

7.

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Annual Report 2014

Silvia Galli

Sing Yee Yeung

Tuerdi Maimaitiyili (enrolled at Lund univeristy)

Ulf Hejman (enrolled at Lund univeristy)

Vida Krikstolaityte (enrolled at vilnius

university, vilnius, Lithuania)

Zahra ElSchich

Michael Braian

Patrick Seumo (enrolled at university

of yaounde I, yaounde, Cameroon)

Peter Lamberg

Pär Johansson

Ramesh Chowdhary

Ricardo Trindade

30


Annual Report 2014

LIST OF RESEARCH ACTIVITIESThe research activities of the Center during 2014 are presented under the headlines below.

In addition Center members are partners in the EU FP7 Marie Curie Initial Training Network “PEPMIP – Robust affinity materials for applications in proteomics and diagnostics” (with Börje Sellergren as Coordinator), EU FP7 Marie Curie Initial Training Network “MagnIM” (Ann Wennerberg), the EU FP7 Marie Curie Initial Training Networks

“Biofuel cells from fundamentals to applications in bioelectrochemistry” (Sergey Shleev), the EU cooperation and mobility programme Erasmus Mundus EMBER (Tautgirdas Ruzgas) and the EU FP7 Marie Curie Initial Training Network Biopolymer Based Food Delivery Systems – BIBAFOODS (Marité Cárdenas Gómez).

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Annual Report 2014

cell-suRfAce inteRActions

Mechanism of Toxicity of Aluminium

based Adjuvant (ABA) Nanomaterials

Funded by the British Medical Research

Council, MRC

pI (principal Investigator): Håkan Eriksson

Analysis of the Cellular and Molecular

Mechanisms of Inflammatory Cells

and Cancer Cells by Using Digital

Holography and Protein Technology

PhD project funded by Malmö

University

Project partner: Phase Holographic

Imaging AB

pI: Anette gjörloff-wingren

Innovative Microscopy and Digital

Holography for Studies of Biomarkers

of Eukaryotic Cells Integrated to

Biosensors and Monitoring Devices

Postdoc project funded by BRCB

Project partner: Phase Holographic

Imaging AB

pI: Anette gjörloff-wingren

Biological Responses NanoSize

Structures

Funded by the Knowledge Foundation

Project partner: Promimic

pI: Ann wennerberg

Hydrophilic and Hydrophobic Implant

Surfaces

Funded by industry

pI: Ann wennerberg

Advanced Surface Characterisation of

New Functional Biomaterials

Funded by the Swedish Research

Council

Project partners: Chalmers and

Dentsply

pI: Ann wennerberg

Development of a Hydrophilic

Nanostructured Abutment Surface to

Promote Soft Tissue Integration

Project partner: Straumann AG

pI: Ryo Jimbo

Imaging of cell surface glycans using

fluorogenic MIP nanoparticles

Funded by Malmö University

pI: Börje Sellergren, Anette gjörloff-wingren

Mechanical behaviour of biological cells


Council

Project partner: Björn Fallqvist, The

Royal Institute of Technology

pI: Martin kroon

1.

moleculAR tRAnspoRt phenomenA

Adjuvants for Products Used in Agriculture

Project partners: AkzoNobel Surface

Chemistry AB

Funded by the Knowledge Foundation,

Malmö University

pI: Johan Engblom

Humectants and Their Mechanisms

in Skin


Project partners: SP AB, ACO Hud

Nordic AB, Eviderm Institute AB

pI: Johan Engblom

2.

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Annual Report 2014

3. moleculAR inteRActions At biointeRfAces

Development of Novel MultiFunctional

Salivary Substitutes for Dry Mouth

Syndrome Patients

Funded by the Swedish Laryng

Foundation, Camurus AB, Malmö

University

pI: Liselott Lindh

Screening of Different Surface Coatings

on Titanium including Different API’s

for Enhanced Wound Healing


Foundation and Malmö University

Project partner: NIOM, Oslo

pI: Liselott Lindh

Surface Modification with Natural

as well as Artificial Active Substances

of Dental Materials with the Aim to

Promote and Keep Good Oral Health

for the Spare Part Human



Project partner: NIOM, Oslo

pI: Liselott Lindh

The Composition of Salivary Films

Formed on Surfaces with Different

Surface Wettability Including

Identification of Pellicle Proteins



pI: Liselott Lindh

Carbohydrate Polymer Water

Interactions: Sorption, Porosity and

Rheology


Project partner: Magle AB, Akzo Nobel

Pulp and Performance Chemicals AB

pI: vitaly kocherbitov

Development of HighResolution

Scanning QCMD Method for Studies

of Hydration of Biofilms

Funded by BRCB

pI: vitaly kocherbitov

Properties of Semifluorinated Alkanes

Funded by Novaliq GmbH

Project partner: Novaliq GmbH

pIs: Johan Engblom, vitaly kocherbitov

Viscoelastic Bioelectrocatalytic

Materials


Council

pIs: Tautgirdas Ruzgas, Thomas Arnebrant

Restorable and Adaptable Surfaces for

Molecular Recognition, Biosensing

and Evanescent Wave Microscopy of

Human Cells


Council

pI: Börje Sellergren

Flexible and Transparent Biofuel Cells

Funded by EU, Marie Curie

Project Partner: Obducat Technologies AB

pI: Sergey Shleev

SelfCharging Biosupercapacitors

Funded by the Swedish Research Council

pI: Sergey Shleev

Devices for NonInvasive Biomedical

Sensing, Monitoring or/and Delivery


Project Partners: Galenica AB, Novosense,

Speximo AB, Bioglan AB

pI: Tautgirdas Ruzgas

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Annual Report 2014

micRobiAl biofilms

Bacterial Acid Tolerance – a New

Target for Fluoridated Milk in Caries

Prevention

Funded by the Borrow Foundation, UK

pIs: gunnel Svensäter, Julia Davies

Novel Biomarkers for Oral Health Care

Funded by Region Skåne (OFRS)

pIs: gunel Svennsäter, Julia Davies, Claes

wickström

Oral Implants – Nanostructures for the

Promotion of Tissue Integration and

Prevention of Infections


Project partners: Noble Biocare AB,

Promimic AB

pIs: gunnel Svensäter, Ann wennerberg

4.

Biomimetic Membranes for Revealing

the Function and Structure Relationship

of Membrane Bound Proteins and other

Biomolecules


Council

pI: Marité Cárdenas gómez

Dental Erosion: Novel Strategies against

an Escalating Problem

Funded by Crafoord Foundation

pI: Javier Sotres

34


Annual Report 2013

SCIENTIFIC INSTRUMENTATION AND EqUIpMENT

opticAl micRoscopY

Contact person: peter FalkmanA Nikon Optiphot EpiFluorescence

microscope equipped with polarizing

filters, phase contrast and a DSU1 digital

camera. A TransferMan NK2 micro

manipulator allows manipulation of sam

ples, such as mounting of AFM colloidal

probes, and a Linkam AnalysaLTS350

temperature controlled stage allows study

of temperatureinduced effects, e.g. lipid

phase transitions.

1.

35


Annual Report 2014

Contact person: Johan Engblom Three alternative thermostated in vitro

diffusion equipments are available in

house, two set ups with flow through

cells (15 + 7 cells) [R.L. Bronaugh & R.F.

Stewart, J. Pharm. Sci. 74 (1985) 64–67]

and 10 static Franz cells [Franz T, J.

Invest. Dermatol. 64 (1975) 190-195].

Solute diffusion over skin, oral mucosa,

nasal mucosa, nails, plant cuticle, as well

as synthetic membranes, has been studied

and assayed spectrophotometrically (on

line) or by HPLCUV. Electrical impedance

spectroscopy has been appended to the

Franz cells as a tool helping to explain

diffusion properties of solutes through

these membranes.

in vitRo diffusion equipment

swAxd

Contact persons: peter Falkman,

Johan EngblomSmall and Wide Angle XRay Scattering.

Kratky compact camera with line col

limation (slit focus), equipped with two

linear Mbraun detectors (small and wide

angle). Temperature controlled sample

stages (0–70°C or 25–300°C). Powder

(semisolid/solid) or capillary (liquid)

sample holders, as well as flowthrough

capillary sample holder.

dsc

Contact person: vitaly kocherbitovDifferential scanning calorimeter DSC1

from MettlerToledo equipped with an

intracooler TC100 and HSS8 sensor.

Temperature range: –90 to +550°C. The

calorimeter can be used to study solid,

soft and liquid substances. Typical sample

masses are 2–10 mg. The DSC can be run

in modulation regime to resolve reversing

and nonreversing heat effects.

5.

2.

3.

4.

ellipsometeR

Contact persons: peter Falkman,

Thomas ArnebrantAn automated Rudolph thin film ellipsom

eter (type 43603-200E, Rudolph Research,

USA) equipped with a xenon arc lamp

as a light source; an interference filter

with UV and infrared blocking (Melles

Griot, The Netherlands) for working at a

wavelength of 4429 Å. The experimental

setup is based on null ellipsometry in the

PCSA arrangement. The components of

the ellipsometer are controlled by means

of the Ellipso software that automatically

measures the ellipsometric angles Psi

and Delta allowing the calculation of the

thickness, refractive index, and adsorbed

mass of the growing films. To perform

experiments in liquid media a peristaltic

pump (Ole Dich Instruments) is used. The

temperature is controlled by means of a

Julabo 5B water bath. Data analysis is

performed with the Ellipsometry software

by Plamen Petrov.

36


Annual Report 2014

qcm-d

Contact person: Sebastian BjörklundThe QSense E4 quartz crystal micro

balance is equipped with the E4 measur

ing chamber that allows simultaneously

running a maximum of four experiments

in the four temperature controlled cells.

Changes in frequency and dissipation are

registered by means of the Eseries elec

tronic unit which is also responsible for

the temperature control. These changes

are related to the adsorbed wet mass and

the viscoelastic properties of the films

adsorbed onto the sensor. The QCMD

is also equipped with an electrochemis

try and an ellipsometry module enabling

the simultaneous measurement of the

electrochemical and optical properties

respectively of the adsorbed films. A four

channels IPC peristaltic pump (Ismatec).

Data analysis is performed with the

QTools software (QSense).

7.

6.

8.

e-sem

Contact persons: peter Falkman, Zoltan BlumScanning Electron Microscope, SEM, Zeiss

EVO LS10. Apart from standard modern

SEM features, i.e. 5 nm pointtopoint

resolution at high vacuum and fully con

ducting samples, the EVO LS10 also offers

environmental control (hence “EVO”). By

controlled water ioele introduction, with

or without the added benefits of a Peltier

Coolstage, fully hydrated samples can be

imaged with accurate sample temperature

control; owing to the high output LaB6

filament and the beam sleeve technology,

the loss in resolution is only tenfold. The

instrument is equipped with the appro

priate detectors and also an INCA EDX

microanalysis system.

spectRoscopic ellipsometeR uvisel hoRibA

Contact person: Marité Cárdenas gómezSpectroscopic ellipsometry is a simple

and fast optical and indirect technique

that offers the possibility to determine

the average thickness of the adsorbed

layer. Ellipsometry measures the ratio

of two values, which is the amplitude

ratio (Ψ=rp/ rs) and the phase difference

between light waves (Δ=Δp-Δs). These

two parameters are defined from the dif

ference in the reflection coefficients for

p and s polarizations and thus in the

optical properties of a material (extinction

co efficient and refractive index). We have

in house an UVISEL HORIBA spectro

scopic ellipsometer covering a wavelength

range of 200 – 820 nm.

37


Annual Report 2014

dls/zetA sizing sYstem

Contact person: peter FalkmanA combined Electrophoretic Light Scat

tering/Dynamic Light Scattering Zeta

potential/particle sizing system w ith a 5

MW 632.8 nm HeNe laser, two insert

able electrodes for high or low voltage,

covering possible electrical field strengths

between 0.25–250 V/cm, and an adjust

able temperature range of 4–100°C. The

instrument has further been fitted with a

Thermaltake Bigwater 760is liquid cool

ing system, to prevent cuvette fogging at

high temperatures.

goniometeR

Contact person: peter FalkmanKruss Goniometer DSA100 Drop shape

ioelect system for measurements of static

and dynamic contact angles. The goniom

eter is equipped with single dosing system

DS3200/3201. Temperature is controlled

in the range 5–90°C using TC30 measur

ing chamber. Humidity is controlled using

HC10 humidity chamber.

Afm

Contact persons: Javier Sotres,

Thomas ArnebrantA Multimode SPM 8 equipped with a

Nanoscope V control unit (Bruker AXS).

The SPM is also equipped with a PicoForce

Unit, a Heater Unit, and the ScanAsyst

and Peak Force Tapping softwares (Bruker

AXS). Furthermore, a digital oscilloscope

(Tektronix TDS 2022C) and a Nikon opti

cal microscope are coupled to the system.

impedAnce meAsuRing equipment

Contact person: Tautgirdas RuzgasFranz cells (Ø=0.90 cm, V=6 ml, PermeGear,

Hellertown, PA, USA) equipped with four

electrodes and connected to a potentiostat

from Ivium Technologies (Eindhoven, The

Netherlands) are used to study impedance

characteristics of membranes, including

skin, leafs, etc. Two platinum wires serve

as working and counter electrodes and two

Ag/AgCl/3M KCl electrodes from World

Precision Instruments (Sarasota, FL, USA)

are used as sensing and reference electrodes.

The equipment allows impedance measure

ments at frequencies up to 6 MHz.

11.

9.

10.

12.

dRop volume AppARAtus

Contact person: Tautgirdas RuzgasDrop Volume Tensiometer TVT 2 consists

of step motor driven syringe including a

needle for droplet formation, setup for opti

cal droplet falling registration, and software

to operate hardware and calculate surface

tension of liquid. This apparatus is used for

determination of surface tension of liquids.

13.

38


Annual Report 2014

RheometeR

Contact persons: vitaly kocherbitov,

peter FalkmanRheometer Bohlin CVO 100 Digital

equipped with Peltier Cylinder C25. The

rheometer system is suitable for research,

product development and quality control.

The rheometer is equipped with 20 mm

parallel plate, cone 4/40 and coaxial cyl

inders measuring systems.

soRption cAloRimeteR

Contact person: vitaly kocherbitovA doubletwin sorption calorimeter for

studies of hydration of powders and

soft materials. The channel diameter

is 28 mm. The calorimeter is equipped

with two sorption cells, each consist of a

sorption chamber (on top) and a vapori

zation chamber (bottom). The cambers

are connected by tubes with varying

diameters to control the ioele flow. The

double twin calorimeter is inserted into

an isothermal TAM 2277 calorimeter

from Thermometric equipped with a

nanoamplifier.

inteRfeRometeR

Contact persons: Ryo Jimbo, Ann

wennerbergWhite light microscopy, horizontal reso

lution 0.3 µm, vertical 0.1 nm, equipped

with a CCD camera, operating also in

phaseshift mode. The main application is

topographical characterisation on the µm

and subµm level. AFM Park Instrument,

surface characterization in the nm level.

Real time PCR Gene expression

pARticle electRophoResis

Contact person: Tautgirdas RuzgasParticle microelectrophoresis apparatus

Mark II (Rank Brothers, Cambridge,

UK) consists of flat electrophoretic cell

equipped with two platinum electrodes

and optical microscope. The apparatus can

be used to determine particle electropho

retic mobility in solution. The mobility can

be used to assess particle zeta potential and

surface charge density. Apparatus allows

measurements with particles bigger than

0.3 µm in diameter.

lAngmuiR suRfAce bAlAnce

Contact persons: Johan Engblom,

Marité Cárdenas gómezKSV 5000 is a programmable Langmuir

and LangmuirBlodgett instrument for

automated Langmuir film experiments and

for deposition of normal or alternating

multilayers onto solid substrates. Surface

pressure is measured using the Wilhelmy

plate method.

14.

15.

16.

17.

18.

39


Annual Report 2014

novAsinA lAbmAsteR-Aw

Contact person: Johan EngblomAn instrument for water activity measure

ments. Accuracy: 0.003 aw (0.3%RH),

range: 3 to 100%RH.

lc-ms

Contact person: Börje SellergrenZQ2000 MS system with 2795 LC and

2996 PDA. The Waters ZQ 2000 LCMS

System is based on the MicromassZQ

2000 Mass Selective Detector. This is a

robust single quadrupole mass spectro

meter, offering characteristic performance

for laboratories that require nominal

mass resolution for mass confirmation

appli cations. This system has a mass

range (amu) up to 2000 daltons. Easily

qualify and quantify small molecules in

a flash with the highly sensitive system.

Both inlet probes are quickly and easily

interchangeable without breaking vacuum.

Flow rates allowed are 5-1000 µl/min (ESI)

and 200–2000 µl/min (APCI).

lc –uv/dAd

Contact person: Börje SellergrenTwo Waters LCUV/DAD 2795/2996

(LCDAD) systems. This robust HPLC

apparatus allows flowrates from 50ul/

min to 5 ml/min for use with 2.1 mm

ID columns and larger. The autosampler

accepts standard 96/384 well plates with

programmable temperature control from

4 to 40°C. A heated column compartment

provides temperatures from 5 degrees

above ambient to 65°C. A range of LC

detectors, like a dual wavelength or PDA

UV detector is optionally available.

solution nmR spectRometeR

Contact person: Börje SellergrenNMR instrument Varian Mercury

400MHz with autosampler. Equipped

with 4 nucleus probe (C, H, P and F) and

probes adjustable to N, B, Si and O.

20.

19.

21.

22.

fluoRchem e

Contact person: Anette gjörloff wingrenHighperformance Western blot and gel

imaging. A selfcontained digital dark

room, compact design with stateoftheart

CCD optical technology, an integrated

computer and simplified touch screen

control. The FluorChem E is built with

imaging speeds and a dynamic range that

surpass film for low femtogram detection

of proteins and DNA in chemiluminescent,

colorimetric and UV fluorescent gels and

blots.

23.

40


Annual Report 2014

biofilm foRmAtion, including AdheRence, detAchment, populAtion diveRsitY And phenotYpic shift

micRobiAl diAgnostics; species And stRAin levels

Contact person: gunnel SvensäterAutoclaves

Anaerobic chamber

Fluorostar

Incubators

Spectrophotometer

PCR

Centrifuges

Contact person: gunnel SvensäterEpifluorescence microscope

Confocal laser scanning microscope

Flow cells with controlled continuous flow

Cell cultures

puRificAtion of mucins And pRoteins

Contact person: gunnel SvensäterFPLC

Preparative electrophores

Ultracentrifuge

pRoteomics, including RAdioActive lAbelling of pRoteins Contact person: gunnel SvensäterMultiphor

Twodimensional electrophoresis

Sonicator

identificAtion of pRoteins

Contact person: gunnel SvensäterImmunohistochemistry

Western blots

ELISA

24.

25.

26.

27.

28.

electRochemicAl equipment

Contact persons: Sergey Shleev,

Tuatgirdas Ruzgas6 potentiostats/galvanostats from Amel,

Autolab, BAS, and Ivium

Unique spectroelectrochemical system

(homemade 10 mL spectroelectrochemi

cal cell, spectrometer HR 4000 CGUV

NIR and light source DH2000 from

Ocean Optics)

Flowinjection analysis

29.

41


Annual Report 2014

COLLABORATIVE pARTNERS OF THE CENTER

industRY collAboRAtoRs

ACO Hud Nordic AB

Acreo AB

A1M Pharma AB

Akzo Noble Pulp and Performance

Chemicals AB

Akzo Nobel Surface Chemistry AB

Amano Enzyme Inc., Japan

Bioglan AB

Biotage AB

Camurus AB

CapSenze HB

Corgio AB

CR Competence AB

Dentsply

Dräger AG, Germany

Enzymatica AB

Eviderm AB

Galenica AB

In vitro Planttech AB

Magle AB

Nares AB

Nobel Biocare AB

Novaliq GmbH, Germany

Novosense AB

Novozymes A/S, Denmark

Obducat Technologies AB

Orbital Systems AB

Promimic AB

Phase Holographic Imaging AB

Samsung, South Korea

SP AB

Speximo AB

Thermo Fischer, UK

Zelmic AB

1.

42


Annual Report 2014

AcAdemic collAboRAtoRs

collAboRAtions with otheR univeRsities And ReseARch institutions

in sweden

Professor Anders Rosén, Cell Biology, university of Linköping

Professor Chris Anderson, Dermatology, university of Linköping

Professor em. Kåre Larsson, Camurus Lipid Research Foundation, Lund

Professor Emma Sparr, physical Chemistry, Lund university

Professor Fredrik Tiberg, Camurus AB, Lund

Professor Fredrik Winquist, Linköping university

Professor Gunnar Dahlén, Dept of Oral Microbiology, university of gothenburg

Professor Jens Schouenborg, Neuronano Research Center, Medical Faculty, Lund university

Professor Karin Schillén, physical Chemistry, Lund university

Professor Knut Irgum, uME, umeå

Professor Kristian Reisbeck, Dept of Medical Microbiology, Lund university

Professor Lars Montelius, Solid State physics, Lund university / INL- International Iberian Nanotechnology Laboratory, portugal

Professor Lo Gorton, Biochemistry, Lund university

Professor Marie Wahlgren, Food Technology, Faculty of Engineering, Lund university

Professor Mark Rutland, The Royal Institute of Technology and Sp AB, Stockholm

Professor Martin Andersson, Dept Applied Chemistry, Chalmers university of Technology, gothenburg

Professor Martin Malmsten, pharmacy, uppsala university

Professor Maud Langton, Swedish university of Agricultural Sciences, uppsala

Professor Olle Söderman, physical Chemistry, Lund university

Professor Pentti Tengvall, Dept Biomaterials, Sahlgrenska Academy, university of gothenburg

Professor Per Claesson, The Royal Institute of Technology and Sp, Stockholm

Professor Per Wollmer, Clinical Sciences, Lund university

Professor Staffan Nilsson, Lund university

2.

43


Annual Report 2014

Professor Thomas Laurell, Lund university

Professor Tomas Albrektsson, Dept Biomaterials, Sahlgrenska Academy, göteborg university

Professor Tommy Nylander, physical Chemistry, Lund university

Professor Torbjörn Bengtsson, Örebro university

Professor Viveka Alfredsson, physical Chemistry, Lund university

Assoc. Professor Malin Sjöö, Food Technology, Lund university

Assoc. Professor Marilyn Rayner, Food Technology, Lund university

Assoc. Professor Mats Eriksson, Linköping university

Assoc. Professor Ola Bergendorff, Dermatology, Lund university

Assoc. Professor Eva Blomberg, The Royal Institute of Technology and Sp AB, Stockholm

Assoc.Professor Peter Siesjö, Department of Clinical Sciences, BMC, Lund university

Per Rabe, Specialist Clinic for Oral Health Care, Hallands Läns Landsting, Halmstad

Doctor Andreas Sonesson, Lund university

Doctor Anna Westerlund, Odontology, gothenburg university

Doctor Annika Krona, The Swedish Institute for Food and Biotechnology, gothenburg

Doctor Bertil Friberg, Brånemark Clinic, gothenburg

Doctor Birgit Brandner, Sp kM AB, Stockholm

Doctor Hanna Wacklin, ESS, Lund

Doctor Jenny Liao Persson, Center for Molecular pathology, Lund university

Doctor Karina Persson, Inst. of Odontology, umeå university

Doctor Maria Lövenklev, The Swedish Institute for Food and Biotechnology, gothenburg

Doctor Marie Skepö, Dept of Theoretical Chemistry, Lund university

Doctor Robert Corkery, The Royal Institute of Technology, Stockholm

Doctor Sylvio Haas, MAX lab, Lund university

Doctor Tomás Plivelic, MAX lab, Lund university

44


Annual Report 2014

inteRnAtionAl collAboRAtions

Professor Ben J. Boyd, Monash Institute of pharmaceutical Sciences, Monash university, Australia

Professor Birger Lindberg Møller, university of Copenhagen, Denmark

Professor Christopher Exley, keele university, uk

Professor David Beighton, guy’s kings and St Thomas’ Dental Institute, Joint Microbiology

Research unit, London, uk

Professor Deirdre Devine, Leeds Dental Institute, uk

Professor Dennis Cvitkovitch, Dept of Microbiology, university of Toronto, Canada

Professor Dietmar Haltrich, universität für Bodenkultur wien, Austria

Professor ECI Veerman, Department of periodontology and Oral Biochemistry, Academic

Centre for Dentistry Amsterdam (ACTA), The Netherlands

Professor Edmond Magner, university of Limerick, Ireland

Professor Gediminas Niaura, vilnius university, Lithuania

Professor Gordon Proctor, kings College, London, uk

Professor Jenny Emnéus, DTu Nanotech, Copenhagen, Denmark

Professor Jeannine Brady, Dept of Oral Biology, university of Florida, gainesville, uSA

Professor Jens Wiltfang, university of Essen, germany

Professor Jon E. Dahl, NIOM, Oslo, Norway

Professor Juozas Kulys, Inst. of Biochemistry, vilnius, Lithuania

Professor Kamal Mustafa, university of Bergen, Norway

Professor Katrin Markus, university of Bochum, germany

Professor Kell Mortensen, university of Copenhagen, Denmark

Professor Leon Rubesaet, uIO, Oslo, Norway

Professor Mark Herzberg, Department of Microbiology, university of Minnesota,

Minneapolis, uSA

45


Annual Report 2014

Professor Markus Wenk, National university of Singapore, Singapore

Professor Ole Jensen, SDu, Odense, Denmark

Professor Peter Cormack, university of Strathclyde, uk

Professor Phil Bartlett, The university of Southampton, uk

Professor Phil Marsh, Health protection Agency, porton Down, uk

Professor Robert Baier, university of Buffalo, Industry/university Cooperative Research Center for Biosurfaces, Buffalo, uSA

Professor Takashe Sawase, Dept prosthodontics, university of Nagasaki, Japan

Professor Vitaliy Khutoryanskiy, university of Reading, uk

Professor Vladimir O. Popov, kurchatov NBIC Centre, Moscow, Russia

Professor Wolfgang Schuhmann, Ruhr-universität Bochum, germany

Research Assoc. Professor Anne Meyer, university of Buffalo, Industry/university Cooperative Research Center for Biosurfaces, Buffalo, uSA

Assoc. Professor Björn Hamberger, university of Copenhagen, Denmark

Assoc. Professor Claus J Løland, university of Copenhagen, Denmark

Assoc. Professor Floris Bikker, ACTA, The Netherlands

Assoc. Professor David Thornton, university of Manchester, uk

Assoc. Professor Jens Risbo, university of Copenhagen, Denmark

Assoc. Professor Lene Jørgensen, university of Copenhagen, Denmark

Assoc. Professor Marco van de Weert, university of Copenhagen, Denmark

Assoc. Professor Marie Ranson, School of Biological Sciences, Scientific Director

– Cancer, Illawarra Health and Medical Research Institute, university of wollongong,

wollongong, Australia

Assoc. Professor Tim TolkerNielsen, university of Copenhagen, Denmark

Assoc. Professor Thomas Günther Pomorski, university of Copenhagen, Denmark

46


Annual Report 2014

Assoc. Professor Seunghwan Lee, Technical university of Denmark, Denmark

Doctor Antonio L. De Lacey, Consejo Superior de Investigaciones Científicas,

Bioelectrocatalysis group, Spain

Doctor Donald Leech, National university of Ireland, galway, Ireland

Doctor Humberto Schwartz, Sao paolo, Brasilien

Doctor JanTore Samuelsen, NIOM, Oslo, Norway

Doctor Magnus Röding, university of South Australia, Australia

Doctor Miguel Alcalde, Consejo Superior de Investigaciones Científicas, Applied

Biocatalysis group, Spain

Doctor Richard Campbel, Institute Laue Langevin, France

Doctor Paulo G. Coelho, Department of Biomimetics, New york university, uSA

Doctor Robert Barker, Institute Laue Langevin, France

Doctor Vida Krikstolaityte, DTu Nanotech, Copenhagen, Denmark

PhD student Nayab Chaudhury, kings College, London, uk

47


Annual Report 2014

pHD THESES SUpERVISED BY CENTER MEMBERS

theses defended

theses in pRogRess

Magnus Falk

Malmö university (Supervisors Sergey

Shleev and Tautgirdas Ruzgas)

“Direct electron transfer based biofuel cells” Dissertation 2014-01-03

Deyar Mahmood

Malmö university (Supervisors: Ann

wennerberg, per vult von Steyern)

“On core and bi-layered all-ceramic

fixed dental prostheses, design and

mechanical properties : studies on stabilized

zirconiumdioxide”Dissertation 2014-03-18

Marjan Dorkhan

Malmö university (Supervisors Julia Davies,

gunnel Svensäter, Ann wennerberg):

“Activities of microbial biofilms on bioactive

implant surfaces” Dissertation 2014-04-04

Ramesh Chowdhart

Malmö university (supervisors Ann

wennerberg, Ryo Jimbo, Liselott Lindh)

“On efficacy of implant thread design for

bone stimulation” Dissertation 2014-05-21

Anton Fagerström

Malmö university (Supervisors Johan

Engblom, vitaly kocherbitov and karin

Bergström (AkzoNobel))

“Bioavailability of active ingredients used in

agriculture”Dissertation 2014-05-28

Peter Lamberg

Malmö university (Supervisors: Tautgirdas

Ruzgas, Thomas Arnebrant, Sergey Shleev)

“Design and characterization of direct elec-

tron transfer based biofuel cells including

tests in cell cultures”Dissertation 2014-09-15

Vida Krikstolaityte

vilnius university (Supervisors: Arunas

Ramanavicius at vilnius university,

Tautgirdas Ruzgas)

“Design and Characterisation of the

electrodes of enzymatic biofuel cells”Dissertation 2014-10-06

Tuerdi Maymaytilli

Faculty of Engineering, Lund university

(Supervisors: per Ståhle, Christina Bjerkén)

Influence of plastic deformation on the

formation and growth of embritteling metal

hydride’s” Start: 2009

Mariko Hayashi

Malmö university (Supervisors: Liselott

Lindh, Ann wennerberg, Ryo Jimbo)

“Biological Responses to Amphiphilic

Nano-size Structures” Start: 2010

48


Annual Report 2014

Cathrine Albér

Malmö university (Supervisors:

Johan Engblom, vitaly kocherbitov,

Marie Lodén, Robert Corkery)

“Humectants and their effects on skin barrier

function – a mechanistic approach” Start: 2010

Zahra ElSchich


Anette gjörloff wingren, Anna ketelsen,

gunilla Nordin Fredrikson)

“Microscopy and digital holography for

real-time applications and imaging: studying

the cellular and molecular mechanisms of

inflammatory cells and cancer cells”Start: 2011

Celina Wierzbicka

Malmö university (Supervisor:

Börje Sellergren, Thomas Arnebrant)

“New approaches to molecularly imprinted

micro- and nanoparticles for post-

translationally modified proteins and protein

fragments” Start: 2012

Dmitrii Pankratov


Sergey Shleev and Zoltan Blum)

“Function of bioelectronic devices in “extra

vivo” situations” Start: 2012

Mark Galat



“Development and characterisation of

molecularly imprinted polymer receptors

targeting pathogenic and biomarker

peptides related to neurodegenerative

diseases” Start: 2013

Sing Yee Yeung



“Restorable and adaptable surfaces for

molecular recognition, biosensing and eva-

nescent wave microscopy of human cells” Start: 2013

Elena Gonzalez


Sergey Shleev and Lars Montelius)

“Flexible and transparent biofuel cells” Start: 2014

Pär Johansson

Malmö university (Supervisors: Ann

wennerberg, Ryo Jimbo, per kjellin)

“On Foreign Body Reactions Around Oral

Implants: The Role of the Inflammation

Balance in Osseointegration”Start: 2013

Silvia Galli

Malmö university (Supervisors: Ryo Jimbo,

Ann wennerberg)

“On the effect of magnesium incorporated

biomaterials for bone regeneration”Start: 2012

Francesca Cecchinato

Malmö university (Supervisors: Ryo Jimbo,

Ann wennerberg)

“Characterisation of magnesium alloys for

oral & maxillofacial applications”Start: 2012

Jonas Anderud


Ann wennerberg, Sten Isaksson,

peter Abrahamsson)

“guided bone regeneration using ceramic

spacemaintaining devices”Start: 2011

49


Annual Report 2014

Michael Braian


Ann wennerberg)

“On the influence of misfit on implant

supraconstructions”Start: 2008

Ricardo Trindade


Ann wennerberg, Ryo Jimbo,

Tomas Albrektsson, pentti Tengvall)

“On Foreign Body Reactions Around Oral

Implants: The Role of the Inflammation

Balance in Osseointegration”Start: 2013

Ali Alenezi

Malmö university (supervisors Ryo Jimbo,

Ann wennerberg, Martin Andersson)

“On enhancement of bone regeneration

using drug delivery agents”Start: 2014

Bruno Chrcanovic

Malmö university Malmö u(supervisors

Tomas Albrektsson, Ann wennerberg,

Björn klinge)

“On risk factors for implant failure”Start: 2013

Patrick Seumo

university of yaoundé I, yaounde,

Camoroon (Supervisors: Ngameni

Emmanuel at university of yaoundé I,

Nanseu Njiki Charles peguy at university

of yaoundé I, Tautgirdas Ruzgas)

“Application of nanoparticles

in electroanalysis”Start: 2010

50


Annual Report 2014

LIST OF pUBLICATIONS AT THE CENTER FROM 2014

Lamberg P, Shleev S, Ludwig R, Arnebrant T, Ruzgas T. Performance of enzymatic fuel cell in cell culture. 2014, Biosens Bioelectron. 55:168-73.

Krikstolaityte V, Barrantes A, Ramanavicius A, Arnebrant T, Shleev S, Ruzgas T. Bioelectrocatalytic reduction of oxygen at gold nanoparticles modified with laccase. 2014, Bioelectrochemistry, 95:1-6.

Dagys, M; Lamberg, P; Shleev, S; Niaura, G; Bachmatova, I; Marcinkeviciene, L; Meskys, R; Kulys, J; Arnebrant, T; Ruzgas, T. Comparison of bioelectrocatalysis at Trichaptum abietinum and Trametes hirsuta laccase modified electrodes. 2014, Electrochim. Acta, 130, 141-147.

Tchekwagep, PMS; NanseuNjiki, CP; Ngameni, E; Arnebrant, T; Ruzgas, T. Quantification of BSA concentration by using Ag electrochemistry in chloride solution: extension of the linear range. 2014, Electrochim. Acta, 135: 351-355.

Krikstolaityte, V; Lamberg, P; Toscano, MD; Silow, M; EicherLorka, O; Ramanavicius, A; Niaura, G; Abariute, L; Ruzgas, T; Shleev, S. Mediatorless Carbohydrate/Oxygen Biofuel Cells with Improved Cellobiose Dehydrogenase Based Bioanode. 2014 Fuel cells, 14: 792-800.

Makaraviciute, A; Ruzgas, T; Ramanavicius, A; Ramanaviciene, A. Antibody fragment immobilization on planar gold and gold nanoparticle modified quartz crystal microbalance with dissipation sensor surfaces for immunosensor applications. 2014, Analytical methods, 6: 2134-2140.

Makaraviciute, A, Ruzgas, T, Ramanavicius, A, Ramanaviciene, A. A QCMD Study of reduced antibody fragments immobilized on planar gold and gold nanoparticle modified sensor surfaces. 2014 Key Eng. Materials, 605: 340-343.

Fagerström A, Kocherbitov V, Westby P, Bergsström K, Arnebrant T and Engblom J. Surfactant softening of plant leaf cuticle model wax – a Differential Scanning Calorimetry (DSC) and Quartz Crystal Microbalance with Dissipation (QCMD) study. J Colloid Interface Sci 426 (2014) 22-30.

Gari H, Rembiesa J, Masilionis I, Vreva N, Svensson B, Sund T, Hansson H, Morén AK, Sjöö M, Wahlgren M, Engblom J and Ruzgas T. Amperometric In Vitro Monitoring of Penetration through Skin Membrane. Electroanalysis. doi: 10.1002/elan.201400426.

Albèr C, BuraczewskaNorin I, Kocherbitov V, Saleem S, Lodèn M and Engblom J. Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics – a doubleblind, randomized and controlled study. International Journal of Cosmetic Science, 2014, 1–7.

Berghaus, M.; Mohammadi, R.; Sellergren, B. Productive encounter: molecularly imprinted nanoparticles prepared using magnetic templates. Chem. Commun. 2014, 50, 8993-8996.

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Kecili, R.; Billing, J.; Nivhede, D.; Sellergren, B.; Rees, A.; Yilmaz, E. Fast identification of selective resins for removal of genotoxic aminopyridine impurities via screening of molecularly imprinted polymer libraries. Journal of Chromatography A. 2014, 1339, 65-72.

Narayanaswamy, P.; Shinde, S.; Sulc, R.; Kraut, R.; Staples, G.; Thiam, C. H.; Grimm, R.; Sellergren, B.; Torta, F.; Wenk, M. R. Lipidomic “Deep Profiling” : An Enhanced Workflow to Reveal New Molecular Species of Signaling Lipids. Anal. Chem. 2014, 86, 3043-3047.

Rossetti, C.; Qader, A. A.; Halvorsen, T. G.; Sellergren, B.; Reubsaet, L. Antibodyfree biomarker determination : exploring molecularly imprinted polymers for progastrin releasing Peptide. Anal. Chem. 2014, 86, 12291–12298.

Kadhirvel, P.; Azenha, M.; Schillinger, E.; Halhalli, M.; Silva, A.; Sellergren, B. Recognitive nanothinfilm composite beads for the enantiomeric resolution of the metastatic breast cancer drug aminoglutethimide. J. Chromatogr. A. 2014, 1358, 93-101.

Qader, A. A.; Urraca, J.; Torsetnes, S. B.; Tönnesen, F.; Reubsaet, L.; Sellergren, B. Peptide imprinted receptors for the determination of the small cell lung cancer associated biomarker progastrin releasing peptide. J. Chromatogr. A. 2014, 1370, 56-62.

Kadhirvel, P.; Azenha, M.; Silva, F.; Sellergren, B. Chromatographycally efficient microspherical composites of molecularly imprinted xerogels deposited inside mesoporous silica. J. Chromatogr. A. 2014, 1355, 158-163.

Nematollahzadeh, A.; Lindemann, P.; Sun, W.; Stute, J.; Lütkemeyer, D.; Sellergren, B. Robust and selective nano cavities for protein separation : An interpenetrating polymer network modified hierarchically protein imprinted hydrogel. J. Chromatogr. A. 2014, 1345, 154-163.

Azenha, M.; Schillinger, E.; Sanmartin, E.; Regueiras, M T.; Silva, F.; Sellergren, B. Vaporphase testing of the memoryeffects in benzene and tolueneimprinted polymers conditioned at elevated temperature. Anal. Chim. Acta 2014, 802, 40-45.

Pankratov, D., Blum, Z., Suyatin, D., Popov, V., Shleev, S. Selfcharging electrochemical biocapacitor. ChemElectroChem 2014, 2, 343-346.

Pankratov, D., Falkman, P., Blum, Z., Shleev, S. Hybrid electric power device for simultaneous generation and storage of electric energy. Energy Environ. Sci. 2014, 7, 989-993.

Pankratov, D., Sotres, J., Barrantes, A., Arnebrant, T., Shleev, S. Interfacial behavior and activity of laccase and bilirubin oxidase on bare gold surfaces. Langmuir 2014, 30, 2943-2951.

Blum, Z., Pankratov, D., Shleev, S. Powering electronic contact lenses: current achievements, challenges, and perspectives. Expert Rev, Ophthalmol, 2014, 9, 269-273.

Pankratov, D., Blum, Z., Shleev, S. Hybrid electric power biodevices. ChemElectroChem. 2014, 1, 1798-1807.

Falk, M., Pankratov, D., Lindh, L., Arnebrant, T., Shleev, S. Miniature direct electron transfer based enzymatic fuel cell operating in human sweat and saliva. Fuel Cells, 2014, 14, 1050-1056.

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Pankratov, D., Sundberg, R., Suyatin, D., Sotres, J., Barrantes, A., Ruzgas, T., Maximov, I., Montelius, L., Shleev, S. The influence of nanoparticles on enzymatic bioelectrocatalysis. RSC Advances, 2014, 4, 38164-38168.

Pita, M., Mate, D., GonzalezPerez, D., Shleev, S., Fernandez, V., Alcalde, M., De Lacey, A. Bioelectrochemical oxidation of water. J. Am. Chem. Soc. 2014, 136, 5892-5895.

Falk, M., Alcalde, M., Bartlett, P.N., De Lacey, A.L., Gorton, L., GutierrezSanchez, C., Haddad, R., Kilburn, J., Leech, D., Ludwig, R., Magner, E., Mate, D., Conghaile, P., Ortiz, R., Pita, M., Poller, S., Ruzgas, T., SalajKosla, U., Schuhmann, W., Sebelius, F., Shao, M., Stoica, L., Sygmund, L., Tilly, J., Toscano, M., Vivekananthan, J., Wright, E., Shleev, S. Selfpowered wireless carbohydrate/oxygen sensitive biodevice based on radio signal transmission. PLoS One, 2014, 9, e109104/1-e109104/9.

Aroonsang W., Sotres J., ElSchich Z., Arnebrant T., Lindh L. Influence of substratum hydrophobicity on salivary pellicles: organization or composition? Biofouling, 2014, 30:1123-32.

Sotres J., Madsen J.B., Arnebrant T., Lee S. Adsorption and nanowear properties of bovine submaxillary mucin films on solid surfaces: Influence of solution pH and substrate hydrophobicity. J. Colloid Interface Sci. 2014, 428:242-250.

Sotres J., Barrantes A., Lindh L., Arnebrant T. 2014. Strategies for a direct characterization of phosphoproteins on hydroxyapatite surfaces. Karger 2014; Caries Research; 2 98-110.

Lindh, L., Aroonsang, W., Sotres, J., Arnebrant, T. Salivary pellicles. Eds. Ligtenberg AJM, Veerman ECI (eds): Saliva. Monogr Oral Sci. Basel, Karger, 2014, vol 24, pp 30–39. DOI: 10.1159/000358782.

T.K Lind, M. Cárdenas, H.P. Wacklin. Formation of Supported Lipid Bilayers by Vesicle Fusion: Effect of Deposition Temperature. Langmuir, 2014, 30, 7259.

S. Mølgaard, M. Henrikson, M. Cárdenas, A. Svagan. Cellulosenanofiber/ polygalacturonic acid coatings with high oxygen barrier and targeted release properties. Carbohydrate Polymers 2014, 114, 179.

Carlstedt J., Wojtasz J., Fyhr P., Kocherbitov V. Hydration and the phase diagram of acid hydrolyzed potato starch. Carbohydrate Polymers 2014; 112, 569–577.

Barauskas, J; Christerson, L; Wadsater, M; Lindstrom, F; Lindqvist, AK; Tiberg, F. Bioadhesive Lipid Compositions : SelfAssembly Structures, Functionality, and Medical Applications. Mol. Pharmaceutics, 2014, 11 (3), pp 895–903. DOI: 10.1021/mp400552.

Kapp SJ, Larsson I, Van De Weert M, Cárdenas M, Jorgensen L. Competitive adsorption of monoclonal antibodies and nonionic surfactants at solid hydrophobic surfaces. J Pharm Sci. 2015 Feb; 104(2):593-601. Doi: 10.1002/jps.24265. Epub 2014 Dec 1.

Osipov E, Polyakov K, Kittl R, Shleev S, Dorovatovsky P, Tikhonova T, Hann S, Ludwig R, Popov V. Effect of the L499M mutation of the ascomycetous Botrytis aclada laccase on redox potential and catalytic properties. Acta Crystallogr D Biol Crystallogr. 2014 Nov; 70 (Pt 11):2913-23. Doi: 10.1107/S1399004714020380. Epub 2014 Oct 23.

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Wadsäter M, Barauskas J, Nylander T, and Tiberg F. Formation of Highly Structured Cubic Micellar Lipid Nanoparticles of Soy Phosphatidylcholine and Glycerol Dioleate and Their Degradation by Triacylglycerol Lipase. ACS Appl. Mater. Interfaces, 2014, 6 (10), pp 7063–7069. DOI: 10.1021/am501489e. Publication Date (Web): April 29, 2014.

D. V. Pankratov, Y. S. Zeifman, A. V. Dudareva, G. K. Pankratova, M. E. Khlupova, Y. M. Parunova, D. N. Zajtsev, N. F. Bashirova, V. O. Popov, and S. V. Shleev. Impact of Surface Modification with Gold Nanoparticles on the Bioelectrocatalytic Parameters of Immobilized Bilirubin Oxidase. Acta Naturae. 2014 JanMar; 6(1): 102–106.

Hansson M, Brandt SS, Lindström J, Gudmundsson P, Jujić A, Malmgren A, Cheng Y. Segmentation of Bmode cardiac ultrasound data by Bayesian Probability Maps Med Image Anal. 2014 Oct; 18(7):1184-99. Doi: 10.1016/j.media.2014.06.004. Epub 2014 Jun 26.

Conlon B, Geoghegan J, Waters E, McCarthy H, Rowe S, Davies JR, Schaeffer C, Foster T, Fey P, O’Gara J (2014). A role for the A domain of unprocessed accumulation associated protein (Aap) in the attachment phase of the Staphylococcus epidermidis biofilm phenotype. J Bacteriol 196:4268-75.

Dorkhan M, Hall J, Uvdal P, Sandell A, Svensäter G, Davies JR. Crystalline anataserich titanium can reduce adherence of oral streptococci. Biofouling 2014; 30:751-759.

Dorkhan M, YucelLindberg T, Hall J, Svensäter G, Davies JR. Adherence of human oral keratinocytes and gingival fibroblasts to nanostructured titanium surfaces. BMC Oral Health 2014; 14:75.

Neilands J, Troedsson U, Sjödin T, Davies JR. The effects of delmopinol and fluoride on acid adaptation and acid production in dental plaque biofilms. Arch Oral Biol 2014; 59:318-323

Svensson D, Westman J, Wickström C, Jönsson D, Herwald H, Nilsson BO. The human endogenous peptide p33 inhibits detrimental effects of LL37 on osteoblast viability J Periodont 2014; doi:10.1111/jre.12184.

Barrantes, A., Arnebrant, T., Lindh, L. Characteristics of saliva films adsorbed onto dental materials studied by QCMD. Colloids and Surfaces A: Physicochem Eng Aspects, 442: 56– 62, 2014 (DOI:http://dx.doi.org/10.1016/j.colsurfa.2013.05.054).

Falck Miniotis, Maria; Mukwaya Anthonny; Gjörloff Wingren Anette. Digital holographic microscopy for noninvasive monitoring of cell cycle arrest in L929 cells. PLoS One 2014; 9:e106546.

Mold, M., Eriksson, H., Siesjö, P., Darabi, A., Shardlow, E. and Exley. C. Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP1 cell line. Scientific Reports, 4, 6287-6293, 2014.

Tovar N, Jimbo R, Marin C, Witek L, Suzuki M, Bonfante EA, Coelho PG. Bone regeneration around implants placed in fresh extraction sockets covered with a duallayer PTFE/collagen membrane: an experimental study in dogs. Int J Periodontics Restorative Dent 2014; 34(6):849-855.

Naito Y, Jimbo R, Bryington MS, Vandeweghe S, Chrcanovic BR, Tovar N, Ichikawa T, Paulo G C, Wennerberg A. The influence of 1α.25dihydroxyvitamin d3 coating on implant osseointegration in the rabbit tibia. J Oral Maxillofac Res 2014; 5(3):e3.

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Anderud J, Jimbo R, Abrahamsson P, Isaksson SG, Adolfsson E, Malmström J, Kozai Y, Hallmer F, Wennerberg A. Guided bone augmentation using a ceramic spacemaintaining device. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 118(5):532-538.

Tovar N, Jimbo R, Witek L, Anchieta R, Yoo D, Manne L, Machado L, Gangolli R, Coelho PG. The physicochemical characterization and in vivo response of micro/ nanoporous bioactive ceramic particulate bone graft materials. Mater Sci Eng C Mater Biol Appl 2014; 43:472-480.

Galli S, Naito Y, Karlsson J, He W, Miyamoto I, Xue Y, Andersson M, Mustafa K, Wennerberg A, Jimbo R .Local release of magnesium from mesoporous TiO2 coatings stimulates the periimplant expression of osteogenic markers and improves osteoconductivity in vivo. Acta Biomater 2014; 10(12):5193-5201.

Johansson P, Jimbo R, Kjellin P, Currie F, Chrcanovic BR, Wennerberg A. Biomechanical evaluation and surface characterization of a nanomodified surface on PEEK implants: a study in the rabbit tibia. Int J Nanomedicine 2014; 9:3903-3911.

Barkarmo S, Andersson M, Currie F, Kjellin P, Jimbo R, Johansson CB, Stenport V. Enhanced bone healing around nanohydroxyapatitecoated polyetheretherketone implants: An experimental study in rabbit bone. J Biomater Appl 2014; 29(5):737-747.

Jimbo R, Janal MN, Marin C, Giro G, Tovar N, Coelho PG. The effect of implant diameter on osseointegration utilizing simplified drilling protocols. Clin Oral Implants Res 2014; 25(11):1295-1300.

Coelho PG, Jimbo R. Osseointegration of metallic devices: current trends based on implant hardware design. Arch Biochem Biophys 2014; 561:99-108.

Sumi T, Takeshita K, Takeichi T, Coelho PG, Jimbo R. Patientspecific gingivacolored abutments: a case series. Int J Periodontics Restorative Dent 2014; 34(4):469-475.

Zambuzzi WF, Bonfante EA, Jimbo R, Hayashi M, Andersson M, Alves G, Takamori ER, Beltrão PJ, Coelho PG, Granjeiro JM. Nanometer scale titanium surface texturing are detected by signaling pathways involving transient FAK and Src activations. PLoS One 2014; 9(7):e95662.

Cuellar JM, Yoo A, Tovar N, Coelho PG, Jimbo R, Vandeweghe S, Kirsch T, Quirno M, Errico TJ. The effects of Amicar and TXA on lumbar spine fusion in an animal model. Spine 2014; 39(19):E1132-1137.

Papia E, Jimbo R, Chrcanovic BR, Andersson M, Vult von Steyern P. Surface structure and mechanical properties of impactionmodified YTZP. Dent Mater 2014; 30(8):808-816.

Coelho PG, Takayama T, Yoo D, Jimbo R, Karunagaran S, Tovar N, Janal MN, Yamano S. Nanometerscale features on micrometerscale surface texturing: a bone histological, gene expression, and nanomechanical study. Bone 2014; 65:25-32.

Jimbo R, Tovar N, Anchieta RB, Machado LS, Marin C, Teixeira HS, Coelho PG. The combined effects of undersized drilling and implant macrogeometry on bone healing around dental implants: an experimental study. Int J Oral Maxillofac Surg 2014; 43(10):1269-1275.

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Jimbo R, Andersson M, Vandeweghe S. Nano in implant dentistry. Int J Dent 2014; 314819.

Jimbo R, Tovar N, Marin C, Teixeira HS, Anchieta RB, Silveira LM, Janal MN, Shibli JA, Coelho PG. The impact of a modified cutting flute implant design on osseointegration. Int J Oral Maxillofac Surg 2014; 43(7):883-888.

Breding K, Jimbo R, Hayashi M, Xue Y, Mustafa K, Andersson M. The effect of hydroxyapatite nanocrystals on osseointegration of titanium implants: an in vivo rabbit study. Int J Dent 2014; 171305.

Jimbo R, Tovar N, Janal MN, Mousa R, Marin C, Yoo D, Teixeira HS, Anchieta RB, Bonfante EA, Konishi A, Takeda K, Kurihara H, Coelho PG. The effect of brainderived neurotrophic factor on periodontal furcation defects. PLoS One 2014; 9(1):e84845.

Cecchinato F, Xue Y, Karlsson J, He W, Wennerberg A, Mustafa K, Andersson M, Jimbo R. In vitro evaluation of human fetal osteoblast response to magnesium loaded mesoporous TiO2 coating. J Biomed Mater Res A 2014; 102(11):3862-3871.

Naito Y, Terukina T, Galli S, Kozai Y, Vandeweghe S, Tagami T, Ozeki T, Ichikawa T, Coelho PG, Jimbo R. The effect of simvastatinloaded polymeric microspheres in a critical size bone defect in the rabbit calvaria. Int J Pharm 2014; 461(1-2):157-162.

Tovar N, Jimbo R, Gangolli R, Witek L, Lorenzoni F, Marin C, Manne L, PerezTroisi L, Baldassarri M, Coelho PG. Modification of xenogeneic graft materials for improved release of P15 peptides in a calvarium defect model. J Craniofac Surg 2014; 25(1):70-76.

Coelho PG, Teixeira HS, Marin C, Witek L, Tovar N, Janal MN, Jimbo R. The in vivo effect of P15 coating on early osseointegration. J Biomed Mater Res B Appl Biomater 2014; 102(3):430-440.

Tovar N, Jimbo R, Gangolli R, Perez L, Manne L, Yoo D, Lorenzoni F, Witek L, Coelho PG. Evaluation of bone response to various anorganic bovine bone xenografts: an experimental calvaria defect study. Int J Oral Maxillofac Surg 2014; 43(2):251-260.

Yoo D, Tovar N, Jimbo R, Marin C, Anchieta RB, Machado LS, Montclare J, Guastaldi FP, Janal MN, Coelho PG. Increased osseointegration effect of bone morphogenetic protein 2 on dental implants: an in vivo study. J Biomed Mater Res A 2014; 102(6):1921-1927.

Wennerberg A, Jimbo R, Stübinger S, Obrecht M, Dard M, Berner S. Nanostructures and hydrophilicity influence osseointegration: a biomechanical study in the rabbit tibia. Clin Oral Implants Res 2014; 25(9):1041-1050.

Chowdhary R, Jimbo R, Thomsen CS, Carlsson L, Wennerberg A. The osseointegration stimulatory effect of macrogeometrymodified implants: a study in the rabbit. Clin Oral Implants Res 2014; 25(9):1051-1055.

Jimbo R, Tovar N, Yoo DY, Janal MN, Anchieta RB, Coelho PG. The effect of different surgical drilling procedures on full laseretched microgrooves surfacetreated implants: an experimental study in sheep. Clin Oral Implants Res 2014; 25(9):1072-1077.

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Anchieta RB, Baldassarri M, Guastaldi F, Tovar N, Janal MN, Gottlow J, Dard M, Jimbo R, Coelho PG. Mechanical Property Assessment of Bone Healing around a TitaniumZirconium Alloy Dental Implant. Clin Implant Dent Relat Res 2014; 16(6):913-919.

Hayashi M, Jimbo R, Xue Y, Mustafa K, Andersson M, Wennerberg A. Photocatalytically induced hydrophilicity influences bone remodelling at longer healing periods: a rabbit study. Clin Oral Implants Res 2014; 25(6):749-754.

Bougas K, Jimbo R, Vandeweghe S, Tovar N, Baldassarri M, Alenezi A, Janal M, Coelho PG, Wennerberg A. In vivo evaluation of a novel implant coating agent: laminin1. Clin Implant Dent Relat Res 2014; 16(5):728-735.

Halldin A, Jimbo R, Johansson CB, Wennerberg A, Jacobsson M, Albrektsson T, Hansson S. Implant stability and bone remodeling after 3 and 13 days of implantation with an initial static strain. Clin Implant Dent Relat Res 2014; 16(3):383-393.

Larsson C, Wennerberg A. The clinical success of zirconiabased crowns: a systematic review. Int J Prosthodont 2014; 27(1):33-43.

Melin Svanborg L, Meirelles L, Franke Stenport V, Kjellin P, Currie F, Andersson M, Wennerberg A. Evaluation of bone healing on sandblasted and acid etched implants coated with nanocrystalline hydroxyapatite – An in vivo study in rabbit femur. Int J Dent. 2014; e197581.

Chrcanovic B, Albrektsson T, Wennerberg A. Reasons for failures of oral implants. J Oral Rehabil. 2014 Jun; 41(6):443-476.

Chrcanovic B, Albrektsson T, Wennerberg A. Flapless versus conventional flapped dental implant surgery: a metaanalysis. PLos One 2014; 20:9(6):e100624.

Chrcanovic B, Albrektsson T, Wennerberg A. Immediate nonfunctional versus immediate functional loading and dental implant failure rates: A systematic review and metaanalysis. J Dent 2014;42(9):1052-1059.

Chrcanovic B, Albrektsson T, Wennerberg A. Prophylactic antibiotic regimen and dental implant failure: a metaanalysis. J Oral Rehabil 2014;41(12):941-956.

Braian M, De Bruyn H, Fransson H, Christersson C, Wennerberg A. Tolerance measurements on internal and externalhexagon implants. Int J Oral Maxillofac Implants 2014;29(4):846-852.

Albrektsson T, Dahlin C, Jemt T, Sennerby L, Turri A, Wennerberg A. Is marginal bone loss around oral implants the result of a provoked foreign body reaction? Clin Implant Dent Relat Res 2014;16(2):155-165.

Chrcanovic BR, Albrektsson T, Wennerberg A. Tilted versus axially placed dental implants: A metaanalysis. J Dent 2014; S0300-5712(14)00261-9.

Chrcanovic BR, Albrektsson T, Wennerberg A. Immediately loaded nonsubmerged versus delayed loaded submerged dental implants: A metaanalysis. Int J Oral Maxillofac Surg. 2014; doi: 10.1016/j.ijom.2014.11.011.

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CONTRIBUTIONS TO AND pARTICIpATION IN CONFERENCES AND wORkSHOpS

oRAl pResentAtions 2014Ann Wennerberg. “Implantates: Superfieces modernas e pesquisas atuais”, 32 CIOSP Congresso Internacional São Paulo, 31 Jan 2014, Brazil. Invited lecture

Ann Wennerberg. “Why does implant fail? Thinking outside the box”, 3 March 2014, George, South Africa. Invited lecture

Ann Wennerberg. Career achievments, WISE Women in Science, 4 Sep 2014, Chalmers University of Technology, Gothenburg, Sweden. Invited lecture

Ann Wennerberg. “How research of today can improve products and treatment results in the future”, Tylösandsdagarna 2014, Joint meeting SFOP and SSPD, 10–12 Sep 2014, Tylösand, Sweden. Invited lecture

Ann Wennerberg. “Dental implants at a mm, mico and nanometer aspect”, DSOI annual meeting, 24 Oct 2014, Vejle, Denmark. Invited lecture

Anette Gjörloff Wingren. “Cells and biomarkers in cancer from conventional methods to innovative digital holographic imaging”. Malmö Cancer Center Retreat 2014, 28–29 August 2014, Båstad, Sweden. Invited lecture

Börje Sellergren. “Molecular Imprinting and adaptable monolayers: Versatile concepts in supramolecular chemistry”, GDCh Minisymposium Supramolecular Polymers, Dec 2014, Essen, Germany. Invited lecture

Börje Sellergren. “Smart capture phases for bioanalysis and discovery“, International Conference on Molecular imprinting, 18–21 Sep 2014, Zhenjiang, China. Invited lecture

Börje Sellergren. “Diagnostic tools based on plastic antibodies”, Innovativ diagnostik för framtiden, Skåne Innovation Week, Medeon, Malmö, June 2014. Invited lecture

Börje Sellergren. “Molecularly imprinted polymers for environmental technologies”, Swiss Federal Institute of Aquatic Science and Technologies, Dec 2014, Zürich, Switzerland. Invited lecture

Börje Sellergren. “Where antibodies fail: Smart capture phases for bioanalysis and discovery”, National University of Singapore, 8 May, 2014, Singapore. Invited lecture

Gunnel Svensäter. “Discovery of new biomarkers and effective interventions”, 23 Apr 2014, Brånemarkkliniken, Göteborg, Sweden. Invited lecture

Gunnel Svensäter. ”Infection control on the biofilm level”, Läkarutbildningen, 10 Nov 2014, Örebro University, Sweden. Invited lecture

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Gunnel Svensäter. “Oral Biofilms and Strategies for Infection Control”, European Society of Endodontology, 17 Oct 2014 Amsterdam, The Netherlands. Invited lecture

Gunnel Svensäter. ”Bakterier på gott och ont”, Akademisk kvart på Stadsbibliotek, 2014, Malmö, Sweden. Invited lecture

Johan Engblom. “A water gradient can be used to regulate biophysical properties of skin and mucosa”, 2nd Pharm. Tech IAPST International Conference on “New insights into diseases and recent therapeutic approaches”, 17–19 Jan 2014, Kolkata, India. Invited lecture

Johan Engblom. “A Water Gradient can be used to Regulate Biophysical Properties of Skin and Mucosa and Impact Drug Transport Monash University”, 24 Jan 2014, Melbourne, Australia. Invited lecture

Julia Davies. ”Oral biofilms”, 14 Feb 2014, Department of Infection Medicine, Lund University, Sweden. Invited lecture

Marité Cárdenas Gómez. “Biomimetic surfaces for membrane bound protein structural and functional studies”, 13th Surface Xray and Neutron Scattering International Conference, 7–11 July 2014. Hamburg, Germany. Invited lecture

Marité Cárdenas Gómez. “Film composition and its relevance in pharmacological formulations”, Open Seminar ESS and MAX IV – new opportunities in formulation research, 9 Jan 2014, Lund, Sweden. Invited lecture

Sergey Shleev. “Hybrid electric power devices for simultaneous generation and storage of electric power” Nanotechnology Conference organized by Lithuanian Academy of Sciences, 16 May 2014, Vilnius, Lithuania. Invited lecture

Tautgirdas Ruzgas. “Nanoelectrochemical sensors, theranostics, and noninvasive sensing”, IVA’s Division for Basic and Interdisciplinary Engineering Sciences, 22 Sep 2014 Stockholm, Sweden. Invited lecture

Vitaly Kocherbitov. “Thermodynamics of biopolymer water interactions”, Technical Chemistry: from Theory to Practice. October 2014, Perm, Russia. Invited plenary

Vitaly Kocherbitov. “Application of scanning methods to distinguish between entropy and enthalpy driven phase transitions”, Interactions in Colloidal Systems: COST action workshop, March 2014, Berlin, Germany. Invited lecture

Dmitry Pankratov. “Hybrid electric devices for simultaneous generation and storage of electric power”, ESEAC2014, 11–15 June 2014, Malmö, Sweden.

Hala Gari. “Amperometric monitoring of drug penetration through skin”, ESEAC2014, 11–15 June 2014, Malmö, Sweden.

Javier Sotres. “Salivary Films – What can we learn from nanomechanical studies?”, 10th European Symposium on Saliva, May 2014, Egmond aan Zee, The Netherlands.

Liselott Lindh. “Influence of substratum hydrophobicity on salivary film composition” 10th European Symposium on Saliva, May 2014, Egmond aan Zee, The Netherlands.

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Patrick Seumo. “Electrochemical determination of total protein concentration”, ESEAC2014, 11–15 June 2014, Malmö, Sweden.

Vida Krikstolaityte. “Mediatorless carbohydrate/oxygen biofuel cells with improved cellobiose dehydrogenase based bioanode”, ESEAC2014, 11-15 June 2014, Malmö, Sweden.

Vitaly Kocherbitov. “Application of sorption calorimetry for studies of hydration of biomolecules”, XVIII conference of International Society for Biological Calorimetry, 1–4 June 2014, Lund, Sweden.

Vitaly Kocherbitov, “Application of humidity scanning QCMD for characterization of sorptiondesorption hysteresis in biopolymers”, 28th ECIS Conference, 7-12 September 2014, Cyprus.

Vitaly Kocherbitov. “Molecular dynamics simulations of nonlamellar liquid crystalline phases of surfactants”, 20th Surfactants in Solution conference, 22–27 June 2014, Coimbra, Portugal.

contAct infoRmAtionbiofilms – research center for biointerfacesMalmö universityFaculty of Health and Society205 06 MalmöSweden

center director : Doctor Anna Holmbergtel : +46 40 665 79 35 e -mail : [email protected]/brcb

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BIOFILMS RESEARCH CENTER FOR BIOINTERFACES€¦ · happy that Michael Braian became Swedish champion in explaining his research and won the competition Forskar Grand Prix organized