R & D of an Innovative Composite Scaffold Incorporated with Phytoestrogenic Icaritin for Treatment of Steroid-associated Osteonecrosis Lesion in Rabbits.

摘要

Bone defect is a common orthopaedic problem caused by many pathologic disorders such as tumor, trauma or metabolic diseases, including osteonecrosis (ON). ON is a disabling clinical condition characterized by the death of osteocytes, aggregation of marrow fat cells, a decrease in activity of bone marrow stem cells (BMSCs) pool, and degeneration of trabecular bone matrix, which affect more frequently young adults that usually leads to bone and articular cartilage destruction in joints, especially in hip and knee. High dose of steroid is one of the risk factors associated with ON, which sometimes is used for treatment of some medical conditions such as systemic lupus erythematosus (SLE), organ transplantation, asthma, rheumatologic arthritis (RA), and severe acute respiratory syndrome (SARS). Core decompression has been efficacious for treatment of early ON stages when the necrotic lesion is still small in size. However, ON lesion, weakens the cancellous bone within and adjacent to the necrotic region. Thus orthopaedic challenges in repair for steroid-associated ON lesion after core decompression may include the impaired osteogenic potential of stem-cell-pool under the influence of pulsed steroid and lack of platform for bone or/and neovascularization ingrowth after removal of large size necrotic bone.;The proposed strategies for treatment of steroid-associated ON lesion are to provide biocompatible scaffold with required structure to fill the defect area after core decompression and osteogenic stimulator facilitating the repair of ON lesion. Previous works show that the PLGA (poly-lactic glycolic acid) and TCP (tricalcium phosphate) have good biocompatibility, osteoconduction and biodegradation to be used in bone defect repair, however no significant osteopromotive effects. Many endogenous factors are osteopromotive and also eventually osteoinductive, such as bone morphogenic proteins (BMPs). As an extraneous molecular, Icaritin, a small molecule derived from Epimedium -derived flavonoids (EF), is found to be able to facilitate matrix calcification, stimulate osteogenesis and inhibit adipogenesis of BMSCs. The present thesis work hypothesizes that the PLGA/TCP incorporating Icaritin to form a porous composite scaffold is osteopromotive and is able to enhance the repair of necrotic bone defect with steroid-associated ON after core decompression.;The findings implied that the porous composite PLGA/TCP/Icaritin scaffold would be an appropriate osteopromotive scaffold implant or bone graft substitute biomaterial for potential application in skeletal tissue engineering. It was the first study to incorporate or homogenize the Chinese herbal molecule into the porous composite biomaterials for medical testing. Though the osteopromotive effect in ON model was observed in vivo, the molecular mechanism of osteogenesis remains for future investigations. (Abstract shortened by UMI.).