IntroductionOne of the main obstacles in the widespread application of gene therapeutic approaches is the necessity for efficient and safe transfection methods. For the introduction of small oligonucleotide gene therapeutics into a target cell, nanoparticle-based methods have been shown to be highly effective and safe. While immune cells are a most interesting target for gene therapy, transfection might influence basic immune functions such as cytokine expression and proliferation, and thus positively or negatively affect therapeutic intervention. Therefore, we investigated the effects of nanoparticle-mediated transfection such as polyethylenimine (PEI) or magnetic beads on immune cell proliferation.MethodsHuman adherent and non-adherent PBMCs were transfected by various methods (e.g. PEI, Lipofectamine® 2000, magnetofection) and stimulated. Proliferation was measured by lymphocyte transformation test (LTT). Cell cycle stages as well as expression of proliferation relevant genes were analyzed. Additionally, the impact of nanoparticles was investigated in vivo in a murine model of the severe systemic immune disease GvHD (graft versus host disease).ResultsThe proliferation of primary immune cells was influenced by nanoparticle-mediated transfection. In particular in the case of magnetic beads, proliferation inhibition coincided with short-term cell cycle arrest and reduced expression of genes relevant for immune cell proliferation. Notably, proliferation inhibition translated into beneficial effects in a murine GvHD model with animals treated with PEI-nanoparticles showing increased survival (pPEI = 0.002) most likely due to reduced inflammation.ConclusionThis study shows for the first time that nanoparticles utilized for gene therapeutic transfection are able to alter proliferation of immune cells and that this effect depends on the type of nanoparticle. For magnetic beads, this was accompanied by temporary cell cycle arrest. Notably, in GvHD this nonspecific anti-proliferative effect might contribute to reduced inflammation and increased survival.
Polytetrafluoroethylene (PTFE) powder is used as a solid lubricant in commercial antifriction coatings. However, most of the matrix polymers are usually not compatible with virgin PTFE resulting in low dispersion and mechanical film stability and adhesion. In our research PTFE TF 2025 was irradiated by g-beam generating PTFE micropowder with persistant radicals and functional groups. These functional groups are able to perform a chemical grafting (cg) of polyamideimide (PAI) and modified PTFE-micropowder by reactive extrusion in melt. Based on grinded extrudates PAI-PTFE-cg dispersions were formulated followed by characterizing dispersion as well as film properties. It was found, that PAI-PTFE-cg dispersion comprises very small PTFE-particles at higher g-irradiation doses in homogeneous dispersions. In addition, all samples showed outstanding film flexibility. Basic tribological properties under mixed lubrication were studied by using a ring-on-disk tribometer. Finally, diluted dispersions were applied to a multi-surface sliding bearing (four segments) for testing in a hydrodynamic plain test bench.
The development of multi-material hybrids by injection molding has been studied very intensively at the IPF in the past. For that, a material bonding between the different substrates was achieved by using a newly developed two-step curing powder coating material as latent reactive adhesive. The aim of the project “Hybrid Pultrusion” was to perform a novel approach for the fabrication of material bonded metal-plastic joints (profiles) in a modified pultrusion process. Therefore, powder pre-coated steel coil is combined with a glass-fiber reinforced epoxy resin matrix. For initial basic studies, the impregnated fiber material has been applied on the pre-coated steel sheets using the Resin Transfer Molding process (RTM-process). It was proved via lap shear tests, that this procedure resulted in very high adhesive strengths up to 35 MPa resulting from the formation of a covalent matrix-steel bonding as well. In addition, the failure mechanism was subsequently studied. Furthermore, by adapting the successful material combination to the pultrusion process it was demonstrated that material bonded hybrids can be achieved even under these continuous processing conditions.
Polyamide (PA), polytetrafluoroethylene (PTFE), and olefinic oils are incompatible. High‐energy radiation in the presence of oxygen can break the PTFE chain, generating hydrophilic functional groups (COF, COOH) and peroxy‐radicals. Based on the functional groups and radicals, it is possible to establish a chemical bond between PA and PTFE as well as between PTFE and olefinic oil molecules. This study prepared PA‐PTFE‐oil‐cb compounds (cb: chemically bonded) by reactive extrusion. The compounds wetting behavior are analyzed by contact angle measurement. Additionally, the sliding properties of the compound are investigated by micro friction testing against stainless steel. Due to good fragmentation and dispersion of PTFE in PA12 matrix, the PA12‐MP1100‐cb and PA12‐MP1100‐MO‐cb compounds show a slight change in wetting behavior compared to virgin PA12. In contrast, the wetting behavior of compounds based on PA46 increases dramatically compared to virgin PA46. Moreover, due to the chemical bonding, the PA‐PTFE‐cb compound surface is significantly smoother than a physical blend used as a model compound. Similarly, the compounds based on PA12 and PA66‐matrix show improved tribological properties compared to PA46‐based compounds. COF values for PA66 and PA12‐Z7321 are 0.69 and 0.55, respectively. In comparison, PA66‐MP1100‐MO‐cb and PA12‐MP1100‐MO‐cb (Z7321) have COF value of 0.34 and 0.38, respectively.
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