@phdthesis{TzonevaVelinova2003, author = {Tzoneva-Velinova, Rumiana}, title = {The wettability of biomaterials determines the protein adsorption and the cellular responses}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001103}, school = {Universit{\"a}t Potsdam}, year = {2003}, abstract = {During the past several decades polymer materials become widely used as components of medical devices and implants such as hemodialysers, bioartificial organs as well as vascular and recombinant surgery. Most of the devices cannot avoid the blood contact in their use. When the polymer materials come in contact with blood they can cause different undesired host responses like thrombosis, inflammatory reactions and infections. Thus the materials must be hemocompatible in order to minimize these undesired body responses. The earliest and one of the main problems in the use of blood-contacting biomaterials is the surface induced thrombosis. The sequence of the thrombus formation on the artificial surfaces has been well established. The first event, which occurs, after exposure of biomaterials to blood, is the adsorption of blood proteins. Surface physicochemical properties of the materials as wettability greatly influence the amount and conformational changes of adsorbed proteins. In turn the type, amount and conformational state of the adsorbed protein layer determines whether platelets will adhere and become activated or not on the artificial surface and thus to complete the thrombus formation. The adsorption of fibrinogen (FNG), which is present in plasma, has been shown to be closely related to surface induced thrombosis by participating in all processes of the thrombus formation such as fibrin formation, platelet adhesion and aggregation. Therefore study the FNG adsorption to artificial surfaces could contribute to better understanding of the mechanisms of platelet adhesion and activation and thus to controlling the surface induced thrombosis. Endothelization of the polymer surfaces is one of the strategies for improving the materials hemocompatibility, which is believed to be the most ideal solution for making truly blood-compatible materials. Since at physiological conditions proteins such as FNG and fibronectin (FN) are the usual extracellular matrix (ECM) for endothelial cells (EC) adhesion, precoating of the materials with these proteins has been shown to improve EC adhesion and growth in vitro. ECM proteins play an essential role not only like a structural support for cell adhesion and spreading, but also they are important factor in transmitting signals for different cell functions. The ability of cells to remodel plasma proteins such as FNG and FN in matrix-like structures together with the classical cell parameters such as actin cytoskeleton and focal adhesion formation could be used as an criteria for proper cell functioning. The establishment and the maintaining of delicate balance between cell-cell and cell-substrate contacts is another important factor for better EC colonization of the implants. The functionality of newly established endothelium in order to produce antithromotic substances should be always considered when EC seeding is used for improving the hemocompatibility of the polymer materials. Controlling the polymer surface properties such as surface wettability represents a versatile approach to manipulate the above cellular responses and therefore can be used in biomaterial and tissue engineering applications for producing better hemocompatible materials.}, language = {en} } @article{LangeBrauneLuetzowetal.2012, author = {Lange, Maik and Braune, Steffen and Luetzow, Karola and Richau, Klaus and Scharnagl, Nico and Weinhart, Marie and Neffe, Axel T. and Jung, Friedrich and Haag, Rainer and Lendlein, Andreas}, title = {Surface functionalization of poly(ether imide) membranes with linear, methylated oligoglycerols for reducing thrombogenicity}, series = {Macromolecular rapid communications}, volume = {33}, journal = {Macromolecular rapid communications}, number = {17}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1336}, doi = {10.1002/marc.201200426}, pages = {1487 -- 1492}, year = {2012}, abstract = {Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers.}, language = {en} } @article{BrauneWalterSchulzeetal.2014, author = {Braune, Steffen and Walter, M. and Schulze, F. and Lendlein, Andreas and Jung, Friedrich}, title = {Changes in platelet morphology and function during 24 hours of storage}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {58}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {1}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-141876}, pages = {159 -- 170}, year = {2014}, abstract = {For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood-and PRP-storage times on changes in platelet morphology and function. Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL - 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 mu m diameter)with increasing storage time. The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials.}, language = {en} } @article{BrauneGrossWalteretal.2016, author = {Braune, Steffen and Gross, M. and Walter, M. and Zhou, Shengqiang and Dietze, Siegfried and Rutschow, S. and Lendlein, Andreas and Tschoepe, C. and Jung, Friedrich}, title = {Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials}, series = {Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials}, volume = {104}, journal = {Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1552-4973}, doi = {10.1002/jbm.b.33366}, pages = {210 -- 217}, year = {2016}, abstract = {On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet—indicating the spreading and activation of the platelets—was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials.}, language = {en} }