Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of...

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Autores principales:	Fu YC, Wang YH, Chen CH, Wang CK, Wang GJ, Ho ML
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/04ccce1fff75454689b7bfbda77f3cc5
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spelling	oai:doaj.org-article:04ccce1fff75454689b7bfbda77f3cc52021-12-02T00:13:00ZCombination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects1178-2013https://doaj.org/article/04ccce1fff75454689b7bfbda77f3cc52015-12-01T00:00:00Zhttps://www.dovepress.com/combination-of-calcium-sulfate-and-simvastatin-controlled-release-micr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid) microspheres (SIM/PLGA) that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS) bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration of bone in the clinical setting.Keywords: calcium sulfate, simvastatin, calvarial bone defects, osteoconductive, osteoinductiveFu YCWang YHChen CHWang CKWang GJHo MLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 7231-7240 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Fu YC Wang YH Chen CH Wang CK Wang GJ Ho ML Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
description	Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid) microspheres (SIM/PLGA) that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS) bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration of bone in the clinical setting.Keywords: calcium sulfate, simvastatin, calvarial bone defects, osteoconductive, osteoinductive
format	article
author	Fu YC Wang YH Chen CH Wang CK Wang GJ Ho ML
author_facet	Fu YC Wang YH Chen CH Wang CK Wang GJ Ho ML
author_sort	Fu YC
title	Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
title_short	Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
title_full	Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
title_fullStr	Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
title_full_unstemmed	Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
title_sort	combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/04ccce1fff75454689b7bfbda77f3cc5
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Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

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