title: Effects of dexamethasone-loaded PLGA microspheres on human fetal osteoblasts.
abstract: Integration of a drug delivery function into implantable medical devices enables local release of specific bioactives to control cells-surface interactions. One alternative to achieve this biofunctionality for bone implants is to incorporate particulate drug delivery systems (DDSs) into the rough or porous implant surfaces. The scope of this study was to assess the effects of a model DDS consisting of poly(D,L-lactide-co-glycolide) (PLGA) microspheres loaded with an anti-inflammatory drug, dexamethasone (DXM), on the response of Simian Virus-immortalized Human Fetal Osteoblast (SV-HFO) cells. The microspheres were prepared by the oil-in-water emulsion/solvent evaporation method, whereas cells response was investigated by Alamar Blue test for viability, alkaline phosphatase (ALP) activity for differentiation, and Alizarin Red staining for matrix mineralization. Cell viability was not affected by the presence of increased concentrations of polymeric microspheres in the culture media. Furthermore, in the cultures with DXM-loaded microspheres, ALP activity was expressed at levels similar with those obtained under osteogenic conditions, indicating that DXM released from the microsphere-stimulated cell differentiation. Matrix mineralization occurred preferentially around the DXM-loaded microspheres confirming that the released DXM could act as osteogenic supplement for the cells. These in vitro findings suggest that a particulate PLGA-DXM DDS may actually provide dual, anti-inflammatory and osteogenic functions when incorporated on the surface of bone implants.
authors.affiliation: Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Mekelweg 2, 2628 CD Delft, The Netherlands.
authors.forename: G J S
authors.initials: GJ
authors.lastname: Dawes
authors.forename: L E
authors.initials: LE
authors.lastname: Fratila-Apachitei
authors.forename: B S
authors.initials: BS
authors.lastname: Necula
authors.forename: I
authors.initials: I
authors.lastname: Apachitei
authors.forename: J P T M
authors.initials: JP
authors.lastname: van Leeuwen
authors.forename: J
authors.initials: J
authors.lastname: Duszczyk
authors.forename: M
authors.initials: M
authors.lastname: Eijken
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants
chemical_list: D000893:Anti-Inflammatory Agents; D020099:Coated Materials, Biocompatible; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D000469:Alkaline Phosphatase