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Blood compatibility of photografted hydrogel coatings
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
2010 (English)In: ACTA BIOMATERIALIA, ISSN 1742-7061, Vol. 6, no 7, 2599-2608 p.Article in journal (Other academic) Published
Abstract [en]

In this work we have evaluated the haemocompatibility of different surface modifications, intended for biomaterials and biosensor applications. Polystyrene slides were coated with thin hydrogel films by self-initiated photografting of four different monomers. The hydrogel surface modifications were thoroughly characterized and tested for their protein resistance and ability to facilitate platelet adhesion and activation of the coagulation system. There was very little protein adsorption from human plasma on the hydrogels formed from poly(ethylene glycol) methacrylate (PEGMA) and 2-hydroxyethyl methacrylate (HEMA). Platelet adhesion tests performed under both static and flow conditions showed that these coatings also demonstrated very high resistance towards platelet adhesion. A small amount of platelets were found to adhere to hydrogels formed from ethylene glycol methyl ether methacrylate (EGMEMA) and 2-carboxyethyl methacrylate (CEA). The polystyrene substrates themselves facilitated large amounts of platelet adhesion under both static and flow conditions. Utilizing a novel setup for imaging of coagulation, it was shown that none of the hydrogel surfaces activated the coagulation system to any great extent. We suggest that this simple fabrication method can be used to produce hydrogel coatings with unusually high blood compatibility, suitable for demanding biomaterials applications.

Place, publisher, year, edition, pages
Elsevier Science B.V. Amsterdam , 2010. Vol. 6, no 7, 2599-2608 p.
Keyword [en]
Hydrogel; Biomaterial; Protein adsorption; Coagulation; Platelet
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-19175DOI: 10.1016/j.actbio.2009.12.046ISI: 000278868000027OAI: oai:DiVA.org:liu-19175DiVA: diva2:223524
Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2011-03-23Bibliographically approved
In thesis
1. Imaging methods for haemostasis research
Open this publication in new window or tab >>Imaging methods for haemostasis research
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Blood is a vital part of the human physiology; a transport system that brings nutrients and oxygen to sustain living cells and simultaneously facilitates the removal of carbon dioxide and other waste products from the body. To assure the continuity of these functions, it is of uttermost importance to keep the flowing blood inside the vascular system at any cost. The principal components of the haemostatic system are the blood platelets and the plasma coagulation system, both working in concert to create a blood stopping haemostatic plug when a vessel is ruptured. In modern health care, methods for treatment and diagnostics often implicate the contact between blood and artificial materials (biomaterials). Biomaterial surfaces may activate platelets and the coagulation cascade by exposing a surface that during blood contact shares certain characteristics with surfaces found at the site of vascular injury. Therefore it is of great importance that the mechanisms behind the interactions between foreign surfaces and blood are studied in order to minimize, and if possible, prevent unnecessary reactions that may lead to thrombosis.

This thesis describes two important methods to study blood – surface interactions in terms of surface induced plasma coagulation and platelet adhesion/aggregation. The method ‘Imaging of coagulation’, a coagulation assay based on time-lapse image capture of the coagulation process was developed during the course of this work. The use of images enables the method to answer questions regarding where coagulation was initiated and how fast coagulation propagates. Such questions are highly relevant in the study of blood-biomaterial interactions but also in general haemostasis research. In vivo, platelet adhesion and aggregation are events that always proceed under flow conditions. Therefore we also developed a cone-and-plate flow model to study these mechanisms under similar conditions in vitro. The cone-and-plate setup was found to be a flexible platform and was used for both blood compatibility testing of potential biomaterials as well as for general haemostasis research.

With the above mentioned methods we tested the haemocompatibility of glycerol monooleate (GMO), a proposed substance for use in biomaterial applications. It was found that GMO did not activate coagulation to any great extent either in plasma or in whole blood.

Surface induced coagulation and platelet adhesion was also studied on PEG-containing hydrogels and compared with hydrogels constructed from three different non-PEG-containing monomers. It was concluded that all the grafted hydrogels, in particular those produced from the monomers 2-hydroxyethyl methacrylate (HEMA) and/or PEG- methacrylate (PEGMA), demonstrated good haemocompatibility.

Supported phospholipid bilayers were used to investigate the relationship between surface charge and procoagulant activity. The coagulation process was studied in a straightforward manner using the imaging of coagulation setup. We concluded that the content of negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-L-serine] (POPS) in the bilayer must exceed ~ 6% for the bilayer to exert procoagulant activity.

The physiological role of factor XII in human haemostasis and thrombosis was investigated in the imaging of coagulation setup and the cone and plate setup by the use of surfaces with thrombogenic coatings. We found that tissue factor initiated coagulation could be greatly accelerated by the presence of contact activating agents in a platelet dependent manner.

In conclusion, the method ‘Imaging of coagulation’ and platelet adhesion/aggregation in the cone-and-plate flow model are both versatile methods with many possible applications. The combination of the two methods provides a solid foundation for biomaterial and haemostasis research.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 61 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1131
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19178 (URN)978-91-7393-621-7 (ISBN)
Public defence
2009-06-01, Aulan, Hälsans hus, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2009-06-12 Created: 2009-06-12 Last updated: 2009-08-21Bibliographically approved
2. Hydrogel coatings for biomedical and biofouling applications
Open this publication in new window or tab >>Hydrogel coatings for biomedical and biofouling applications
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many applications share a substantial and yet unmet need for prediction and control of interactions between surfaces and proteins or living cells. Examples are blood-contacting biomaterials, biosensors, and non-toxic anti-biofouling coatings for ship hulls. The main focus of this thesis work has been the synthesis, characterization and properties of a group of coatings, designed for such applications. Many types of substrates, particularly plastics, were coated directly with ultrathin, hydrophilic polymer coatings, using a newly developed polymerization method initiated by short-wavelength ultraviolet light.

The thesis contains eight papers and an introduction aimed to provide a context for the research work. The common theme, discussed and analyzed throughout the work, has been the minimization of non-specific binding of proteins to surfaces, thereby limiting the risk of uncontrolled attachment of cells and higher organisms. This has mainly been accomplished through the incorporation of monomer units bearing poly(ethylene glycol) (PEG) side chains in the coatings. Such PEG-containing “protein resistant” coatings have been used in this work as matrices for biosensor applications, as blood-contacting inert surfaces and as antibiofouling coatings for marine applications, with excellent results. The properties of the coatings, and their interactions with proteins and cells, have been thoroughly characterized using an array of techniques such as infrared spectroscopy, ellipsometry, atomic force microscopy, surface plasmon resonance and neutron reflectometry. In addition, other routes to fabricate coatings with high protein resistance have also been utilized. For instance, the versatility of the fabrication method has enabled the design of gradients with varying electrostatic charge, affecting the protein adsorption and leading to protein resistance in areas where the charges are balanced.

This thesis also describes a novel application of imaging surface plasmon resonance for the investigation of the surface exploration behavior of marine biofouling organisms, in particular barnacle larvae. This technique allows for real-time assessment of the rate of surface exploration and the deposition of protein-based adhesives onto surfaces, a process which was previously very difficult to investigate experimentally. In this thesis, the method was applied to several model surface chemistries, including the hydrogels described above. The new method promises to provide insights into the interactions between biofouling organisms and a surface during the critical stages prior to permanent settlement, hopefully facilitating the development of antibiofouling coatings for marine applications.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 74 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1302
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-54304 (URN)978-91-7393-435-0 (ISBN)
Public defence
2010-03-19, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 00:00 (English)
Opponent
Supervisors
Available from: 2010-03-08 Created: 2010-03-08 Last updated: 2017-01-11Bibliographically approved

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Faxälv, LarsEkblad, TobiasLiedberg, BoLindahl, Tomas L.

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Clinical ChemistryFaculty of Health SciencesDepartment of Clinical ChemistrySensor Science and Molecular Physics The Institute of Technology
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