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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
Steroid-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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111223/ https://www.ncbi.nlm.nih.gov/pubmed/25968462 http://dx.doi.org/10.1016/j.biomaterials.2015.04.038 |
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author | Qin, Ling Yao, Dong Zheng, Lizhen Liu, Wai-Ching Liu, Zhong Lei, Ming Huang, Le Xie, Xinhui Wang, Xinluan Chen, Yang Yao, Xinsheng Peng, Jiang Gong, He Griffith, James F. Huang, Yanping Zheng, Yongping Feng, Jian Q. Liu, Ying Chen, Shihui Xiao, Deming Wang, Daping Xiong, Jiangyi Pei, Duanqing Zhang, Peng Pan, Xiaohua Wang, Xiaohong Lee, Kwong-Man Cheng, Chun-Yiu |
author_facet | Qin, Ling Yao, Dong Zheng, Lizhen Liu, Wai-Ching Liu, Zhong Lei, Ming Huang, Le Xie, Xinhui Wang, Xinluan Chen, Yang Yao, Xinsheng Peng, Jiang Gong, He Griffith, James F. Huang, Yanping Zheng, Yongping Feng, Jian Q. Liu, Ying Chen, Shihui Xiao, Deming Wang, Daping Xiong, Jiangyi Pei, Duanqing Zhang, Peng Pan, Xiaohua Wang, Xiaohong Lee, Kwong-Man Cheng, Chun-Yiu |
author_sort | Qin, Ling |
collection | PubMed |
description | Steroid-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 P/T 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 COL1α, osteocalcin, RUNX2, and BMP-2 while inhibited adipogenesis related genes C/EBP-ß, PPAR-γ, and aP2 of rabbit BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in vitro and in vivo but a higher expression of migration related gene VCAM1 was only found in P/T/I group 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. |
format | Online Article Text |
id | pubmed-7111223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71112232020-04-02 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 Qin, Ling Yao, Dong Zheng, Lizhen Liu, Wai-Ching Liu, Zhong Lei, Ming Huang, Le Xie, Xinhui Wang, Xinluan Chen, Yang Yao, Xinsheng Peng, Jiang Gong, He Griffith, James F. Huang, Yanping Zheng, Yongping Feng, Jian Q. Liu, Ying Chen, Shihui Xiao, Deming Wang, Daping Xiong, Jiangyi Pei, Duanqing Zhang, Peng Pan, Xiaohua Wang, Xiaohong Lee, Kwong-Man Cheng, Chun-Yiu Biomaterials Article Steroid-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 P/T 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 COL1α, osteocalcin, RUNX2, and BMP-2 while inhibited adipogenesis related genes C/EBP-ß, PPAR-γ, and aP2 of rabbit BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in vitro and in vivo but a higher expression of migration related gene VCAM1 was only found in P/T/I group 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. Elsevier Ltd. 2015-08 2015-05-15 /pmc/articles/PMC7111223/ /pubmed/25968462 http://dx.doi.org/10.1016/j.biomaterials.2015.04.038 Text en Copyright © 2015 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Qin, Ling Yao, Dong Zheng, Lizhen Liu, Wai-Ching Liu, Zhong Lei, Ming Huang, Le Xie, Xinhui Wang, Xinluan Chen, Yang Yao, Xinsheng Peng, Jiang Gong, He Griffith, James F. Huang, Yanping Zheng, Yongping Feng, Jian Q. Liu, Ying Chen, Shihui Xiao, Deming Wang, Daping Xiong, Jiangyi Pei, Duanqing Zhang, Peng Pan, Xiaohua Wang, Xiaohong Lee, Kwong-Man Cheng, Chun-Yiu 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111223/ https://www.ncbi.nlm.nih.gov/pubmed/25968462 http://dx.doi.org/10.1016/j.biomaterials.2015.04.038 |
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