Injectable Cell- and Growth Factor-Free Poly(4-hydroxybutyrate) (P4HB) Microspheres with Open Porous Structures and Great Efficiency of Promoting Bone Regeneration.

Delivering injectable microspheres in a minimally invasive way to repair complexly shaped tissue defects renders them attractive for clinical use. Especially, open porous microspheres that provide sufficient internal space for cell proliferation and nutrient diffusions can efficiently aid to completing reconstructions of tissue defects. In this work, chemically synthesized and biodegradable poly(4-hydroxybutyrate) (P4HB), which is the U.S. FDA-approved polyhydroxyalkanoate (PHA), was employed for fabricating open porous microspheres using a double-emulsion solvent evaporation method. The influences of fabrication parameters were discussed. It was found that the P4HB-based cell-free and growth factor-free open porous microspheres can enhance osteoblast differentiation of adipose-derived stem cells in vitro and accelerate rat calvarial bone-defect healing in vivo. These results demonstrated that the injectable open porous P4HB microspheres present a remarkable potential in bone tissue regeneration.