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- ItemEffects of BDNF and PEC Nanoparticles on Osteocytes(Basel : MDPI, 2020) Loy, Thomas Leonhard; Vehlow, David; Kauschke, Vivien; Müller, Martin; Heiss, Christian; Lips, Katrin SusanneBone substitute materials loaded with mediators that stimulate fracture healing are demanded in the clinical treatment in trauma surgery and orthopedics. Brain-derived neurotrophic factor (BDNF) enhances the proliferation and differentiation of mesenchymal stem cells into osteoblast. To load the implants with BDNF, a drug delivery system that allows the release of BDNF under spatiotemporal control would improve functionality. Polyelectrolyte complex nanoparticles (PECNP) have been reported as a suitable drug delivery system. The suitability of PECNP in contact with osteocytes as the main cell type of bone is not known so far. Thus, we aimed to verify that BDNF and PECNP loaded with BDNF (PECNP+BDNF) as well as pure PECNP have no negative effects on osteocytes in vitro. Therefore, the murine osteocyte cell line MLO-Y4 was treated with BDNF and PECNP+BDNF. The effects on proliferation were analyzed by the BrdU test (n = 5). The results demonstrated a significant increase in proliferation 24 h after BDNF application, whereas PECNP+BDNF did not lead to significant changes. Thus, we conclude that BDNF is an appropriate mediator to stimulate osteocytes. Since the addition of PECNP did not affect the viability of osteocytes, we conclude that PECNP are a suitable drug delivery system for bone implants. © 2020 by the authors.
- ItemSolubility and selectivity effects of the anion on the adsorption of different heavy metal ions onto chitosan(Basel : MDPI, 2020) Weißpflog, Janek; Gündel, Alexander; Vehlow, David; Steinbach, Christine; Müller, Martin; Boldt, Regine; Schwarz, Simona; Schwarz, DanaThe biopolymer chitosan is a very efficient adsorber material for the removal of heavy metal ions from aqueous solutions. Due to the solubility properties of chitosan it can be used as both a liquid adsorber and a solid flocculant for water treatment reaching outstanding adsorption capacities for a number of heavy metal ions. However, the type of anion corresponding to the investigated heavy metal ions has a strong influence on the adsorption capacity and sorption mechanism on chitosan. In this work, the adsorption capacity of the heavy metal ions manganese, iron, cobalt, nickel, copper, and zinc were investigated in dependence on their corresponding anions sulfate, chloride, and nitrate by batch experiments. The selectivity of the different heavy metal ions was analyzed by column experiments. © 2020 by the authors.
- ItemThermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib(Basel : Molecular Diversity Preservation International, 2019) Reis, Berthold; Vehlow, David; Rust, Tarik; Kuckling, Dirk; Müller, MartinTo overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly(N-isoproplyacrylamide-co-dimethylaminoethylmethacrylate) (P(NIPAM-co-DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemHigh concentrations of polyelectrolyte complex nanoparticles decrease activity of osteoclasts(Basel : MDPI, 2019) Kauschke, Vivien; Hessland, Felix Maximilian; Vehlow, David; Müller, Martin; Heiss, Christian; Lips, Katrin SusanneFracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implantmaterials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles can serve as drug delivery systems for growth factors like Brain-Derived Neurotrophic Factor (BDNF), which stimulated osteoblast differentiation. Therefore, polyelectrolyte complex nanoparticles (PEC-NPs) consisting of poly(l-lysine) (PLL) and cellulose sulfate (CS), with or without addition of BDNF, were used to analyze their effect on osteoclasts in vitro. Live cell images showed that osteoclast numbers decreased after application of high PLL/CS PEC-NPs concentrations independent of whether BDNF was added or not. Real-time RT-PCR revealed that relative mRNA expression of cathepsin K and calcitonin receptor significantly declined after incubation of osteoclasts with high concentrations of PLL/CS PEC-NPs. Furthermore, Enzyme-Linked Immunosorbent Assay indicated that tartrate-resistant acidic phosphatase 5b activity was significantly reduced in the presence of high PLL/CS PEC-NPs concentrations. Consistent with these results, the pit formation analysis showed that less hydroxyapatite was resorbed by osteoclasts after incubation with high concentrations of PLL/CS PEC-NPs. BDNF had no influence on osteoclasts. We conclude that highly concentrated PLL/CS PEC-NPs dosages decreased osteoclastogenesis and osteoclasts activity. Moreover, BDNF might be a promising growth factor for osteoporotic fracture treatment since it did not increase osteoclast activity. © 2019 by the authors.