Exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair.
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.
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. xl.wang@siat.ac.cn
Xin-Luan
XL
Wang
Xin-Hui
XH
Xie
Ge
G
Zhang
Shi-Hui
SH
Chen
Dong
D
Yao
Kai
K
He
Xiao-Hong
XH
Wang
Xin-Sheng
XS
Yao
Yang
Y
Leng
Kwok-Pui
KP
Fung
Kwok-Sui
KS
Leung
Ling
L
Qin
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002130:Calcium Phosphates / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D005419:Flavonoids / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010020:Osteonecrosis / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D048789:Phytoestrogens / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D051381:Rats; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
D002130:Calcium Phosphates; D005419:Flavonoids; D048789:Phytoestrogens; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C018392:tricalcium phosphate; C499403:icaritin