Carbonate Apatite\nHoneycomb Scaffold-Based Drug Delivery\nSystem for Repairing Osteoporotic Bone Defects

Osteoporotic bone defects are difficult to repair in\nelderly patients.\nThis study aimed to repair osteoporotic bone defects using a combination\nof bone tissue engineering (BTE) and drug delivery systems (DDS).\nHerein, honeycomb granules (HCGs) composed of carbonate apatite microspheres\nwere fabricated as BTE scaffolds. Each HCG possesses hexagonal macropores\nand abundant interconnected micropores between the microspheres. Owing\nto these multiscale interconnected pores, HCGs can readily contain\nantibodies against sclerostin (Scl), which causes imbalances in bone\nhomeostasis. Anti-Scl antibody-loaded HCGs (Scl-Ab-HCGs) regulate\nthe release of Scl-Abs in response to the pH of the osteoporotic environment.\nIn ovariectomized rabbit osteoporotic femurs, HCG monotherapy forms\nnew bone with less osteocyte damage (fewer empty bone lacunae) and\nfewer osteoclasts than osteoporotic bone; however, it is insufficient\nto prevent receptor activator of nuclear factor-kappa B ligand (RANKL)\noverexpression. Consequently, HCG monotherapy restores bone quantity\nbetter than no treatment but not to normal levels. In contrast, new\nbone tissue formed by Scl-Ab-HCG-based DDS predominantly expresses\nosteocalcin rather than RANKL, similar to normal bone, and shows a\nsimilar osteocyte apoptosis level, bone quantity, and osteoclast number\nas normal bone. Thus, Scl-Ab-HCG-based DDS is a promising approach\nfor osteoporotic bone defect repair.