Sr-HA-graft-Poly(γ-benzyl-L-glutamate) Nanocomposite Microcarriers: Controllable Sr2+ Release for Accelerating Osteogenenisis and Bony Nonunion Repair

The microcarrier system offers an attractive method for cellular amplification and phenotype enhancement in the field of bone tissue engineering. However, it remains a challenge to fabricate porous microcarriers with osteoinductive activity for speedy and high-quality osseointegration in regeneration of serious complication of bone fracture, like nonunion. Here, we present a facile method for the first time manufacture microcarriers with osteogenic effects and properties based on well controlled and long-term Sr2+ release. At first, strontium-substituted hydroxyapatite was prepared (Sr-HA) and a novel Sr-HA-graft-poly(gamma-benzyl-l-glutamate) (Sr-HA-PBLG) nanocomposite was synthesized. Then, the microcarriers with highly interconnected macropores were fabricated by a double emulsion method, which allowed cells to adhere and proliferate and secrete extracellular matrix. Besides, the microcarriers with a relatively uniform diameter of 271.5 +/- 45.0 mu m are feasible for injection. The Sr-HA-PBLG microcarriers efficiently promoted osteogenic gene expression in vitro. With injection of the Sr-HA-PBLG microcarriers loading adipose derived stem cells (ADSCs) into the nonunion sites, bone regeneration was observed at 8 weeks after injection in a mice model.