Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits
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AbstractSteroid-associated osteonecrosis (SAON) may lead to joint collapse and subsequent joint replacement. Poly lactic-co-glycolic acid/tricalcium phosphate (P/T) scaffold providing sustained release of icaritin (a metabolite of Epimedium-derived flavonoids) was investigated as a bone defect filler after surgical core-decompression (CD) to prevent femoral head collapse in a bipedal SAON animal model using emu (a large flightless bird). The underlying mechanism on SAON was evaluated using a well-established quadrupedal rabbit model. Fifteen emus were established with SAON, and CD was performed along the femoral neck for the efficacy study. In this CD bone defect, a PIT scaffold with icaritin (P/T/I group) or without icaritin (P/T group) was implanted while no scaffold implantation was used as a control. For the mechanistic study in rabbits, the effects of icaritin and composite scaffolds on bone mesenchymal stem cells (BMSCs) recruitment, osteogenesis, and anti-adipogenesis were evaluated. Our efficacy study showed that P/T/I group had the significantly lowest incidence of femoral head collapse, better preserved cartilage and mechanical properties supported by more new bone formation within the bone tunnel. For the mechanistic study, our in vitro tests suggested that icaritin enhanced the expression of osteogenesis related genes COL1 alpha, osteocalcin, RUNX2, and BMP-2 while inhibited adipogenesis related genes C/EBP-beta, PPAR-gamma, and aP2 of rabbit BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in vitro in vitro. In conclusion, both efficacy and mechanistic studies show the potential of a bioactive composite porous P/T scaffold incorporating icaritin to enhance bone defect repair after surgical CD and prevent femoral head collapse in a bipedal SAON emu model. (C) 2015 Elsevier Ltd. All rights reserved.
All Author(s) ListQin L, Yao D, Zheng LZ, Liu WC, Liu Z, Lei M, Huang L, Xie XH, Wang XL, Chen Y, Yao XS, Peng J, Gong H, Griffith JF, Huang YP, Zheng YP, Feng JQ, Liu Y, Chen SH, Xiao DM, Wang DP, Xiong JY, Pei DQ, Zhang P, Pan XH, Wang XH, Lee KM, Cheng CY
Journal nameBiomaterials
Detailed descriptiondoi:10.1016/j.biomaterials.2015.04.038.
Year2015
Month8
Day1
Volume Number59
PublisherELSEVIER SCI LTD
Pages125 - 143
ISSN0142-9612
eISSN1878-5905
LanguagesEnglish-United Kingdom
KeywordsBioactive composite porous scaffold; Bipedal emus; Hip collapse; Phytomolecule icaritin; Steroid-associated osteonecrosis
Web of Science Subject CategoriesEngineering; Engineering, Biomedical; Materials Science; Materials Science, Biomaterials

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