Incorporation of protein-loaded microspheres into chitosan-polycaprolactone scaffolds for controlled release

► Growth factor is entrapped into chitosan microspheres for local release. ► Microsphere-embedded scaffolds can control the release without severe burst. ► Scaffolds made of chitosan-based copolymer have desirable strength in wet state. ► Scaffolds administrate the release over an extended period longer than four weeks. ► Pore parameters of scaffolds instead of microspheres regulate release rates. Chitosan microspheres loaded with transforming growth factor-β1 (TGF-β1) were first prepared with an emulsification method using genipin as crosslinker, and the selected microspheres were then embedded into porous scaffolds built by chitosan-polycaprolactone with polycaprolactone content of around 42wt.%. Some optimized chitosan-polycaprolactone scaffolds with porosity higher than 80% and having an initial TGF-β1 load of around 3ng(TGF-β1)/mg(dry scaffold) were capable of maintaining sustained release of TGF-β1 in a simulant in vivo environment at controlled rates over a period of time longer than four weeks without severely initial burst. The chitosan-polycaprolactone scaffolds also showed well-defined compressive properties in wet state with compressive stress at 10% strain and modulus higher than 100kPa and 1000kPa, respectively, which are almost ten-fold higher than that of corresponding microsphere-embedded chitosan scaffolds. The obtained results suggest that potential applications of the scaffolds in articular cartilage repair.