Sequential release of bioactive IGF-I and TGF-β1 from PLGA microsphere-based scaffolds

Growth factors have become an important component for tissue engineering and regenerative medicine. Insulin-like growth factor-I (IGF-I) and transforming growth factor-betal (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. (c) 2007 Elsevier Ltd. All rights reserved.