@phdthesis{Devine2013, author = {Devine, Eric}, title = {Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83583}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {A large number of metabolic waste products accumulate in the blood of patients with renal failure. Since these solutes have deleterious effects on the biological functions, they are called uremic toxins and have been classified in three groups: 1) small water soluble solutes (MW < 500 Da), 2) small solutes with known protein binding (MW < 500 Da), and 3) middle molecules (500 Da < MW < 60 kDa). Protein bound uremic toxins are poorly removed by conventional hemodialysis treatments because of their high protein binding and high distribution volume. The prototypical protein bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are associated with the progression of chronic kidney disease, cardiovascular outcomes, and mortality of patients on maintenance hemodialysis. Furthermore, these two compounds are bound to albumin, the main plasma protein, via electrostatic and/or Van-der-Waals forces. The aim of the present thesis was to develop a dialysis strategy, based on the reversible modification of the ionic strength in the blood stream by increasing the sodium chloride (NaCl) concentration, in order to enhance the removal of protein bound substances, such as IS and pCS, with the ultimate goal to improve clinical patient outcomes. Enhancing the NaCl concentration ([NaCl]) in both human normal and uremic plasma was efficient to reduce the protein bound fraction of both IS and pCS by reducing their binding affinity to albumin. Increasing the ionic strength was feasible during modified pre-dilution hemodiafiltration (HDF) by increasing the [NaCl] in the substitution fluid. The NaCl excess was adequately removed within the hemodialyzer. This method was effective to increase the removal rate of both protein bound uremic toxins. Its ex vivo hemocompatibility, however, was limited by the osmotic shock induced by the high [NaCl] in the substituate. Therefore, modified pre-dilution HDF was further iterated by introducing a second serial cartridge, named the serial dialyzers (SDial) setup. This setting was validated for feasibility, hemocompatibility, and toxin removal efficiency. A better hemocompatibility at similar efficacy was obtained with the SDial setup compared with the modified pre-dilution HDF. Both methods were finally tested in an animal sheep model of dialysis to verify biocompatibility. Low hemolysis and no activation of both the complement and the coagulation systems were observed when increasing the [NaCl] in blood up to 0.45 and 0.60 M with the modified pre-dilution HDF and the SDial setup, respectively. In conclusion, the two dialysis methods developed to transitory enhance the ionic strength in blood demonstrated adequate biocompatibility and improved the removal of protein bound uremic toxins by decreasing their protein bound fraction. The concepts require follow-on clinical trials to assess their in vivo efficacy and their impact on long-term clinical outcomes.}, subject = {H{\"a}modiafiltration}, language = {en} } @article{HolstHolstHirschfelderetal.2012, author = {Holst, Alexandra Ioana and Holst, Stefan and Hirschfelder, Ursula and von Seckendorff, Volker}, title = {Retrieval analysis of different orthodontic brackets: the applicability of electron microprobe techniques for determining material heterogeneities and corrosive potential}, series = {Journal of applied oral science}, volume = {20}, journal = {Journal of applied oral science}, number = {4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130415}, pages = {478- 485}, year = {2012}, abstract = {Objective: The objective of this study was to investigate the applicability of microanalytical methods with high spatial resolution to the characterization of the composition and corrosion behavior of two bracket systems. Material and methods: The surfaces of six nickel-free brackets and six nickel-containing brackets were examined for signs of corrosion and qualitative surface analysis using an electron probe microanalyzer (EPMA), prior to bonding to patient's tooth surfaces and four months after clinical use. The surfaces were characterized qualitatively by secondary electron (SE) images and back scattered electron (BSE) images in both compositional and topographical mode. Qualitative and quantitative wavelength-dispersive analyses were performed for different elements, and by utilizing qualitative analysis the relative concentration of selected elements was mapped two-dimensionally. The absolute concentration of the elements was determined in specially prepared brackets by quantitative analysis using pure element standards for calibration and calculating correction-factors (ZAF). Results: Clear differences were observed between the different bracket types. The nickel-containing stainless steel brackets consist of two separate pieces joined by a brazing alloy. Compositional analysis revealed two different alloy compositions, and reaction zones on both sides of the brazing alloy. The nickel-free bracket was a single piece with only slight variation in element concentration, but had a significantly rougher surface. After clinical use, no corrosive phenomena were detectable with the methods applied. Traces of intraoral wear at the contact areas between the bracket slot and the arch wire were verified. Conclusion: Electron probe microanalysis is a valuable tool for the characterization of element distribution and quantitative analysis for corrosion studies.}, language = {en} } @article{KowalewiczVorndranFeichtneretal.2021, author = {Kowalewicz, Katharina and Vorndran, Elke and Feichtner, Franziska and Waselau, Anja-Christina and Brueckner, Manuel and Meyer-Lindenberg, Andrea}, title = {In-vivo degradation behavior and osseointegration of 3D powder-printed calcium magnesium phosphate cement scaffolds}, series = {Materials}, volume = {14}, journal = {Materials}, number = {4}, issn = {1996-1944}, doi = {10.3390/ma14040946}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228929}, year = {2021}, abstract = {Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca\(_{0.75}\)Mg\(_{2.25}\)(PO\(_4\))\(_2\)) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, {\O} = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further.}, language = {en} } @article{KrieterJeyaseelanRuethetal.2021, author = {Krieter, Detlef H. and Jeyaseelan, Jarline and R{\"u}th, Marieke and Lemke, Horst-Dieter and Wanner, Christoph and Drechsler, Christiane}, title = {Clinical hemocompatibility of double-filtration lipoprotein apheresis comparing polyethersulfone and ethylene-vinyl alcohol copolymer membranes}, series = {Artificial Organs}, volume = {45}, journal = {Artificial Organs}, number = {9}, doi = {10.1111/aor.13944}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258307}, pages = {1104-1113}, year = {2021}, abstract = {Activation of the complement system and leukocytes by blood-membrane interactions may further promote arteriosclerosis typically present in patients on lipoprotein apheresis. As clinical data on the hemocompatibility of lipoprotein apheresis are scarce, a controlled clinical study comparing two different types of plasma separation and fractionation membranes used in double-filtration lipoprotein apheresis was urgently needed, as its outcome may influence clinical decision-making. In a prospective, randomized, crossover controlled trial, eight patients on double-filtration lipoprotein apheresis were subjected to one treatment with recent polyethersulfone (PES) plasma separation and fractionation membranes and one control treatment using a set of ethylene-vinyl alcohol copolymer (EVAL) membranes. White blood cell (WBC) and platelet (PC) counts, complement factor C5a and thrombin-antithrombin III (TAT) concentrations were determined in samples drawn at defined times from different sites of the extracorporeal blood and plasma circuit. With a nadir at 25 minutes, WBCs in EVAL decreased to 33.5 ± 10.7\% of baseline compared with 63.8 ± 22.0\% at 20 minutes in PES (P < .001). The maximum C5a levels in venous blood reentering the patients were measured at 30 minutes, being 30.0 ± 11.2 µg/L with EVAL and 12.3 ± 9.0 µg/L with PES (P < .05). The highest C5a concentrations were found in plasma after the plasma filters (EVAL 56.1 ± 22.0 µg/L at 15 minutes vs PES 23.3 ± 15.2 µg/L at 10 minutes; P < .001). PC did not significantly decrease over time with both membrane types, whereas TAT levels did not rise until the end of the treatment without differences between membranes. Regarding lipoprotein(a) and low-density lipoprotein (LDL) cholesterol removal, both membrane sets performed equally. Compared with EVAL, PES membranes cause less leukocyte and complement system activation, the classical parameters of hemocompatibility of extracorporeal treatment procedures, at identical treatment efficacy. Better hemocompatibility may avoid inflammation-promoting effects through blood-material interactions in patients requiring double-filtration lipoprotein apheresis.}, language = {en} } @article{MechauFrankBakircietal.2021, author = {Mechau, Jannik and Frank, Andreas and Bakirci, Ezgi and Gumbel, Simon and Jungst, Tomasz and Giesa, Reiner and Groll, J{\"u}rgen and Dalton, Paul D. and Schmidt, Hans-Werner}, title = {Hydrophilic (AB)\(_{n}\) Segmented Copolymers for Melt Extrusion-Based Additive Manufacturing}, series = {Macromolecular Chemistry and Physics}, volume = {222}, journal = {Macromolecular Chemistry and Physics}, number = {1}, doi = {10.1002/macp.202000265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224513}, year = {2021}, abstract = {Several manufacturing technologies beneficially involve processing from the melt, including extrusion-based printing, electrospinning, and electrohydrodynamic jetting. In this study, (AB)\(_{n}\) segmented copolymers are tailored for melt-processing to form physically crosslinked hydrogels after swelling. The copolymers are composed of hydrophilic poly(ethylene glycol)-based segments and hydrophobic bisurea segments, which form physical crosslinks via hydrogen bonds. The degree of polymerization was adjusted to match the melt viscosity to the different melt-processing techniques. Using extrusion-based printing, a width of approximately 260 µm is printed into 3D constructs, with excellent interlayer bonding at fiber junctions, due to hydrogen bonding between the layers. For melt electrospinning, much thinner fibers in the range of about 1-15 µm are obtained and produced in a typical nonwoven morphology. With melt electrowriting, fibers are deposited in a controlled way to well-defined 3D constructs. In this case, multiple fiber layers fuse together enabling constructs with line width in the range of 70 to 160 µm. If exposed to water the printed constructs swell and form physically crosslinked hydrogels that slowly disintegrate, which is a feature for soluble inks within biofabrication strategies. In this context, cytotoxicity tests confirm the viability of cells and thus demonstrating biocompatibility of this class of copolymers.}, language = {en} } @article{SulimanSunPedersenetal.2016, author = {Suliman, Salwa and Sun, Yang and Pedersen, Torbjorn O. and Xue, Ying and Nickel, Joachim and Waag, Thilo and Finne-Wistrand, Anna and Steinm{\"u}ller-Nethl, Doris and Krueger, Anke and Costea, Daniela E. and Mustafa, Kamal}, title = {In vivo host response and degradation of copolymer scaffolds functionalized with nanodiamonds and bone morphogenetic protein 2}, series = {Advanced Healthcare Materials}, volume = {5}, journal = {Advanced Healthcare Materials}, number = {6}, doi = {10.1002/adhm.201500723}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189764}, pages = {730-742}, year = {2016}, abstract = {The aim is to evaluate the effect of modifying poly[(L-lactide)-co-(epsilon-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1 alpha 2, and ANGPT1 are signifi cantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90\% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates infl ammation while lowering the dose of BMP-2 to a relatively safe and economical level.}, language = {en} }