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Title: Interaction between immobilized polyelectrolyte complex nanoparticles and human mesenchymal stromal cells
Authors: Woltmann, B.Torger, B.Müller, M.Hempel, U.
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Issue Date: 2014
Published in: International Journal of Nanomedicine Vol. 9 (2014), No. 1
Publisher: Auckland : DOVE Medical Press
Abstract: Background: Implant loosening or deficient osseointegration is a major problem in patients with systemic bone diseases (eg, osteoporosis). For this reason, the stimulation of the regional cell population by local and sustained drug delivery at the bone/implant interface to induce the formation of a mechanical stable bone is promising. The purpose of this study was to investigate the interaction of polymer-based nanoparticles with human bone marrow-derived cells, considering nanoparticles' composition and surface net charge. Materials and methods: Polyelectrolyte complex nanoparticles (PECNPs) composed of the polycations poly(ethyleneimine) (PEI), poly(L-lysine) (PLL), or (N,N-diethylamino)ethyldextran (DEAE) in combination with the polyanions dextran sulfate (DS) or cellulose sulfate (CS) were prepared. PECNPs' physicochemical properties (size, net charge) were characterized by dynamic light scattering and particle charge detector measurements. Biocompatibility was investigated using human mesenchymal stromal cells (hMSCs) cultured on immobilized PECNP films (5-50 nmol·cm-2) by analysis for metabolic activity of hMSCs in dependence of PECNP surface concentration by MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay, as well as cell morphology (phase contrast microscopy). Results: PECNPs ranging between ~50 nm and 150 nm were prepared. By varying the ratio of polycations and polyanions, PECNPs with a slightly positive (PEC+NP) or negative (PEC-NP) net charge were obtained. The PECNP composition significantly affected cell morphology and metabolic activity, whereas the net charge had a negligible influence. Therefore, we classified PECNPs into "variant systems" featuring a significant dose dependency of metabolic activity (DEAE/CS, PEI/DS) and "invariant systems" lacking such a dependency (DEAE/DS, PEI/CS). Immunofluorescence imaging of fluorescein isothiocyanate isomer I (FITC)-labeled PECNPs suggested internalization into hMSCs remaining stable for 8 days. Conclusion: Our study demonstrated that PECNP composition affects hMSC behavior. In particular, the PEI/CS system showed biocompatibility in a wide concentration range, representing a suitable system for local drug delivery from PECNP-functionalized bone substitute materials.
Keywords: Biocompatibility; Mesenchymal stromal cells; Morphology; MTS assay; Polyelectrolyte complex nanoparticles; (n,n diethylamino)ethyldextran; cellulose sulfate; dextran derivative; dextran sulfate; nanoparticle; polyethyleneimine; polylysine; unclassified drug; electrolyte; nanoparticle; polymer; article; biocompatibility; cell interaction; cell metabolism; cell structure; chemical composition; controlled study; fluorescence imaging; human; human cell; immobilization; internalization; mesenchymal stroma cell; molecular interaction; particle size; physical chemistry; scanning force microscopy; surface charge; adsorption; cell size; comparative study; cytology; dose response; drug effects; materials testing; mesenchymal stroma cell; metabolism; static electricity; ultrastructure; Adsorption; Cell Size; Dose-Response Relationship, Drug; Electrolytes; Humans; Materials Testing; Mesenchymal Stromal Cells; Nanoparticles; Particle Size; Polymers; Static Electricity
DDC: 570
License: CC BY-NC 3.0 Unported
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