Determination of dual delivery for stem cell differentiation using dexamethasone and TGF-β3 in/on polymeric microspheres

Abstract

In this work, a cocktail of dexamethasone (Dex) and transforming growth factor-β3 (TGF-β3) bound with heparin in/on PLGA microspheres was investigated by local dual delivery using rabbit mesenchymal stem cells (rMSCs) for chondrogenic differentiation in in vitro and in vivo study. In this study, we proved that the microsphere constructs were capable of simultaneously releasing TGF-β3-conjugated with cy5.5 and Dex-conjugated with FITC with approximately zero order kinetics determined by Kodak imaging and confocal laser microscope. Microsphere constructs containing TGF-β3 and Dex showed a significantly higher number of specific lacunae phenotypes at the end of the 4 week study irrespective of the presence of dexamethasone and TGF-β3. Thus, dual delivery of TGF and Dex can be used to engineer inflammation-free and cartilage-associate tissue in the transplanted PLGA construct into nude mouse. These heparin-bound TGF-β3-coated and Dex-loaded PLGA microsphere constructs show promise as coatings for implantable biomedical devices to improve biocompatibility and ensure both in vitro and in vivo performance.