title: Sequential release of bioactive IGF-I and TGF-beta 1 from PLGA microsphere-based scaffolds.
abstract: Growth factors have become an important component for tissue engineering and regenerative medicine. Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta 1) in particular have great significance in cartilage tissue engineering. Here, we describe sequential release of IGF-I and TGF-beta 1 from modular designed poly(l,d-lactic-co-glycolic acid) (PLGA) scaffolds. Growth factors were encapsulated in PLGA microspheres using spontaneous emulsion, and in vitro release kinetics was characterized by ELISA. Incorporating BSA in the IGF-I formulations decreased the initial burst from 80% to 20%, while using uncapped PLGA rather than capped decreased the initial burst of TGF-beta 1 from 60% to 0% upon hydration. The bioactivity of released IGF-I and TGF-beta 1 was determined using MCF-7 proliferation assay and HT-2 inhibition assay, respectively. Both growth factors were released for up to 70 days in bioactive form. Scaffolds were fabricated by fusing bioactive IGF-I and TGF-beta 1 microspheres with dichloromethane vapor. Three scaffolds with tailored release kinetics were fabricated: IGF-I and TGF-beta 1 released continuously, TGF-beta 1 with IGF-I released sequentially after 10 days, and IGF-I with TGF-beta 1 released sequentially after 7 days. Scaffold swelling and degradation were characterized, indicating a peak swelling ratio of 4 after 7 days of incubation and showing 50% mass loss after 28 days, both consistent with scaffold release kinetics. The ability of these scaffolds to release IGF-I and TGF-beta 1 sequentially makes them very useful for cartilage tissue engineering applications.
authors.affiliation: Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Jaklenec
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hinckfuss
authors.forename: Bahar
authors.initials: B
authors.lastname: Bilgen
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Ciombor
authors.forename: Roy
authors.initials: R
authors.lastname: Aaron
authors.forename: Edith
authors.initials: E
authors.lastname: Mathiowitz
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002850:Chromatography, Gel; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D053773:Transforming Growth Factor beta1 / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D053773:Transforming Growth Factor beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I