title: Interaction between immobilized polyelectrolyte complex nanoparticles and human mesenchymal stromal cells.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dresden University of Technology, Faculty of Medicine Carl Gustav Carus, Institute of Physiological Chemistry, Dresden, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Woltmann
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Department of Polyelectrolytes and Dispersions, Dresden, Germany ; Dresden University of Technology, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Torger
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Department of Polyelectrolytes and Dispersions, Dresden, Germany ; Dresden University of Technology, Department of Chemistry and Food Chemistry, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: Dresden University of Technology, Faculty of Medicine Carl Gustav Carus, Institute of Physiological Chemistry, Dresden, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
mesh_terms: D000327:Adsorption; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000494:pharmacology*; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure*; D010316:Particle Size; D011108:Polymers / Q000494:pharmacology*; D055672:Static Electricity
chemical_list: D004573:Electrolytes; D011108:Polymers
keywords: MTS assay; biocompatibility; mesenchymal stromal cells; morphology; polyelectrolyte complex nanoparticles