title: Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.
abstract: Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules.
authors.affiliation: Particulate Fluids Processing Centre, Department of Chemical and Biomolecular Engineering, University of Melbourne, Parkville, 3010, Victoria, Australia; Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, 3010, Victoria, Australia.
authors.forename: Dewi P
authors.initials: DP
authors.lastname: Go
authors.forename: Jason A
authors.initials: JA
authors.lastname: Palmer
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Mitchell
authors.forename: Sally L
authors.initials: SL
authors.lastname: Gras
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D001681:Biological Assay; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005453:Fluorescence; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014364:Tryptophan / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000521:alpha-MSH; D014364:Tryptophan
keywords: anti-inflammatory; fibroblast growth factor; foreign body response; surface modifications; tissue engineering