Fabrication and characterization of injectable thermosensitive hydrogel containing dipyridamole loaded polycaprolactone nanoparticles for bone tissue engineering

Entrapping osteogenic agents in in-situ forming scaffolds is an effective strategy to promote bone repair. In this study, thermo-sensitive chitosan (CS)/Silk fibroin (SF) hydrogels associated with dipyridamole (DIP) loaded polycaprolactone nanoparticles (DIP-PCL NPs) were prepared for the localized controlled delivery of DIP. DIPPCL NPs were prepared using the solvent-emulsification evaporation method and the effects of different formulation variables on the properties of NPs were evaluated using the irregular factorial design. Then, the optimized NPs were dispersed into the in-situ gel and characterized for the in-vitro gelation time, pH, mechanical properties, and rheological properties. The optimized DIP-PCL NPs showed the particle size of 349.53 +/- 8.20 nm, the polydispersity index of 0.34 +/- 0.12, the zeta potential of -1.89 +/- 0.10 mV, drug loading of 26.25 +/- 0.37%, the encapsulation efficiency of 89.20 +/- 0.49% and the release efficiency of 30.04 +/- 1.49%. Among various prepared hydrogel systems, the hydrogel composed of 2% (w/v) CS with 0.5% (w/v) ss-glycerophosphate and 0.5% (w/v) SF showed the minimum gelation time and the highest mechanical strength. In-vitro release study also showed that DIP could be sustained released from the system. Cell culture study also revealed that the proliferation and differentiation of the cells treated with the DIP-PCL NPs -CS2/SF0.5 hydrogel were higher than those treated with DIP-PCL NPs at all-time intervals. The superior performance of the DIP-PCL- CS2/SF0.5 hydrogel indicated that this system could be useful for bone tissue engineering.