Recombinant human transforming growth factor-β1 (TGF-β1) was incorporated into biodegradable microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) at 6 ng per mg microparticle. Fluorescein isothiocynate-labelled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5 wt%) and buffer pH (3, 5, or 7.4) on TGF-β1 release kinetics and PLGA degradation were determined in vitro for up to 28 days. TGF-β1 was released in a multi-phasic fashion including an initial burst effect. Increasing the PEG content resulted in decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at acidic buffer pH, which led to decreased protein release rates. PLGA degradation was also enhanced at 5% PEG, which was significantly accelerated at acidic pH conditions. Co-encapsulation of TGF-β1 with FITC-Dextran reduced the initial burst effect as compared to FITC-BSA. The TGF-β1 released from PLGA/PEG microparticles enhanced the proliferation and osteoblastic differentiation of marrow stromal cells cultured on poly(propylene fumarate) (PPF) substrates. The cells showed significantly increased total cell number, alkaline phosphatase (ALPase) activity, and osteocalcin production after 21 days, as compared to cells cultured under control conditions without TGF-β1. These results suggest that PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-β1, which may find applications in modulating cellular response during bone healing at a skeletal defect site.
ASJC Scopus subject areas
- Chemical Engineering(all)