Controlled delivery of platelet-derived growth factor-BB from injectable microsphere/hydrogel composites

Platelet-derived growth factor-BB (PGDF-BB) loaded gelatin microspheres with an average size of about 2   μm was incorporated into chitosan/silk fibroin/glycerophosphate (GP) solutions to prepare composites. The formulated composite solutions were able to form into hydrogels in a temperature range between 32 and 37   °C at a pH of ca.7. They had good fluidity at 25   °C and showed shear-thinning features at both 25 and 37   °C, revealing that they are injectable at room temperature. Elastic modulus of some composites at 37   °C was about 10-fold higher than that of chitosan/GP gel, confirming that these composites behave like mechanically strong gels. Optimal composites showed abilities to administrate PDGF-BB release in an approximately linear manner up to 5 weeks. The PDGF-BB release could be regulated by the PDGF-BB load and the silk fibroin content in the composites in an individual or cooperative way. In vivo degradation of composites demonstrated that some of them had markedly enhanced degradation endurance as compared to the chitosan/GP gel. PDGF-BB-stimulated DNA synthesis in Balb/c 3T3 fibroblasts and PDGF-BB-induced cell migration suggested that the bioactivity of released PDGF-BB was well retained.