phytoestrogens and Osteonecrosis

This study was designed to develop a bioactive scaffold to enhance bone defect repair in steroid-associated osteonecrosis (SAON). Icaritin, a metabolite of the herb Epimedium, has been identified as an angiogenic and osteogenic phytomolecule. Icaritin was homogenized into poly lactic-co-glycolic acid/tricalcium phosphate (PLGA/TCP) to form an icaritin-releasing porous composite scaffold (PLGA/TCP/icaritin) by fine-spinning technology. In vitro, high performance liquid chromatography was used to determine the release of icaritin during degradation of PLGA/TCP/icaritin. The osteogenic effects of PLGA/TCP/icaritin were evaluated using rat bone marrow mesenchymal stem cells (BMSCs). In vivo, the osteogenic effect of PLGA/TCP/icaritin was determined within a bone tunnel after core decompression in SAON rabbits and angiography within scaffolds was examined in rabbit muscle pouch model. In vitro study confirmed the sustainable release of icaritin from PLGA/TCP/icaritin with the bioactive scaffold promoting the proliferation and osteoblastic differentiation of rat BMSCs. In vivo study showed that PLGA/TCP/icaritin significantly promoted new bone formation within the bone defect after core decompression in SAON rabbits and enhanced neovascularization in the rabbit muscle pouch experiment. In conclusion, PLGA/TCP/icaritin is an innovative local delivery system that demonstrates sustainable release of osteogenic phytomolecule icaritin enhancing bone repair in an SAON rabbit model. The supplement of scaffold materials with bioactive phytomolecule(s) might improve treatment efficiency in challenging orthopedic conditions.

Topics: Animals; Bone Marrow Cells; Calcium Phosphates; Cells, Cultured; Disease Models, Animal; Femoral Fractures; Flavonoids; Fracture Healing; Lactic Acid; Male; Neovascularization, Physiologic; Osteogenesis; Osteonecrosis; Phytoestrogens; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Rats; Tissue Engineering; Tissue Scaffolds

This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model.. Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically.. The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group.. PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.

Topics: Adrenal Cortex Hormones; Animals; Epimedium; Femur; Lipid Metabolism; Magnetic Resonance Imaging; Male; Osteonecrosis; Phytoestrogens; Phytotherapy; Plant Preparations; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Thrombosis