Abstract
Osteoporotic fracture is one of the most common bone diseases in middle and old age, as the most serious consequence of osteoporosis. Sclerostin single-chain antibody fragments (SCL-scFv) have been proven to promote bone formation by binding to scleroprotein, a natural antagonist of the Wnt pathway, but it is difficult to rule alone due to the weak permeability and immunogenicity. Herein, we prepared poly(lactic-co-glycolic acid) microspheres as a sustained-release vehicle to prolong the activity of SCL-scFv. The morphology of microspheres were uniform and nearly sphere, loading efficiency and encapsulation efficiency of SCL-scFv microspheres were 6.28 ± 1.04% and 48.37 ± 8.11%, respectively. Approximately 90% of the SCL-scFvs were released from the microspheres over 28 days with initial burst releasing (38%) in the first 4 days. Sustained-release of active SCL-scFv from microspheres promoted bone marrow mesenchymal stem cells osteogenic differentiation in vitro and enhanced fracture healing in ovariectomized rats by improving bone mass and bone formation in the fracture region. All these findings demonstrate that the microspheres are able to simultaneously achieve localized long-term SCL-scFv controlled release and effectively promote bone formation, which provides a promising approach for osteoporotic fracture.