title: Design and characterization of core-shell mPEG-PLGA composite microparticles for development of cell-scaffold constructs.
abstract: Appropriate scaffolds capable of providing suitable biological and structural guidance are of great importance to generate cell-scaffold constructs for cell-based tissue engineering. The aim of the present study was to develop composite microparticles with a structure to provide functionality as a combined drug delivery/scaffold system. Composite microparticles were produced by incorporating either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate (Alg/CS/DS) particles in mPEG-PLGA microparticles using coaxial ultrasonic atomization. The encapsulation and distribution of Alg/DS or Alg/CS/DS particles in the mPEG-PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core-shell composite microparticles containing the Alg/DS particles or the Alg/CS/DS particles displayed 40% and 65% DS release in 10 days, respectively, as compared to the DS directly loaded microparticles showing 90% DS release during the same time interval. The release profiles of DS correlate with the cell proliferation of fibroblasts, i.e. more sustainable cell growth was induced by the DS released from the core-shell composite microparticles comprising Alg/CS/DS particles. After seeding fibroblasts onto the composite microparticles, excellent cell adhesion was observed, and a successful assembly of the cell-scaffold constructs was induced within 7 days. Therefore, the present study demonstrates a novel strategy for fabrication of core-shell composite microparticles comprising additional particulate drug carriers in the core, which provides controlled delivery of DS and favorable cell biocompatibility; an approach to potentially achieve cell-based tissue regeneration.
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: Yanhong
authors: Y
authors: Wen
authors: Monica Ramos
authors: MR
authors: Gallego
authors: Lene Feldskov
authors: LF
authors: Nielsen
authors: Lene
authors: L
authors: Jorgensen
authors: Eva Horn
authors: EH
authors: Møller
authors: Hanne Mørck
authors: HM
authors: Nielsen
mesh_terms: D000464:Alginates / Q000009:adverse effects / Q000737:chemistry / Q000648:ultrastructure; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000009:adverse effects / Q000737:chemistry; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D020723:Glucuronic Acid / Q000009:adverse effects / Q000737:chemistry; D048091:Guided Tissue Regeneration / Q000009:adverse effects; D006603:Hexuronic Acids / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D008422:Materials Testing; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000009:adverse effects / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000464:Alginates; D000925:Anticoagulants; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D003871:Dermatan Sulfate; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D048271:Chitosan
keywords: Biopolymers; Composite microparticles; Core–shell structure; Glycosaminoglycans (GAGs); Scaffold design; Sustained drug delivery; Tissue regeneration