title: Fabrication of core-shell microcapsules using PLGA and alginate for dual growth factor delivery system.
abstract: To effectively harness the great potential of stem cells, we designed a dual growth factor delivery system for the application toward stem cell differentiation into specific lineages. This system carries a core-shell structure within microcapsules made of poly(L-lactide-co-glycolide) (PLGA) and alginate, which were fabricated using a coaxial electro-dropping method. Both PLGA and alginate were supplied from the inner and outer nozzles, respectively. The size and shape of microcapsules were greatly varying depending on the variables: nozzle size, applied voltage, volumetric feeding ratio (PLGA:alginate), feeding rate, and polymer concentrations. Once proper conditions were met, single or multi PLGA cores were found settled within the microcapsules. From the microscopic images, wrinkled surfaces of microcapsules were observed, along with the PLGA cores inside the alginate domain. When two different microcapsules were made, switching the position of bone morphogenetic protein (BMP)-2 and dexamethasone (Dex) for either core or shell domain, their release profiles were very unique on a temporal basis, based on their location in the microcapsules. An initial burst of biomolecules was highly suppressed when either biomolecule was loaded in the PLGA core. It was clear that the osteogenic biomolecules encapsulated in the microcapsule could be released together and their concentrations were disparate at each time point. Meanwhile as the hydrogel constructs including rat bone marrow stromal cells (BMSCs) and osteogenic factor-loaded microcapsules were cultured for up to 4 weeks, the gene expressions levels of osteopontin, type I collagen, and osteocalcin were significantly upregulated as compared to the control group. The present coaxial system was very effective in manufacturing PLGA core-alginate shell microcapsules and in encapsulating multiple biomolecules essential for stem cell differentiation.
authors.affiliation: Biomaterials Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Choi
authors.forename: Chul Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Ik Hwan
authors.initials: IH
authors.lastname: Kim
authors.forename: Heung Jae
authors.initials: HJ
authors.lastname: Chun
authors.forename: Kwideok
authors.initials: K
authors.lastname: Park
authors.forename: Dong Keun
authors.initials: DK
authors.lastname: Han
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D002214:Capsules; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D015870:Gene Expression / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D002214:Capsules; D004337:Drug Carriers; D004338:Drug Combinations; D006603:Hexuronic Acids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D020723:Glucuronic Acid