Combined Delivery of Two Different Bioactive Factors Incorporated in Hydroxyapatite Microcarrier for Bone Regeneration
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Online ISSN 2212-5469
ORIGINAL ARTICLE
Combined Delivery of Two Different Bioactive Factors Incorporated in Hydroxyapatite Microcarrier for Bone Regeneration Tae-Woo Kim1 • Woo-Beom Ahn1 • Joong-Min Kim1,2 • Joong-Hyun Kim3,4,5 Tae-Hyun Kim4,5 • Roman A. Perez4,5,6 • Hyon-Seok Jang1
•
Received: 9 February 2020 / Revised: 3 March 2020 / Accepted: 24 March 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020
Abstract BACKGROUND: The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process. METHODS: Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (a-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8 weeks, and samples were harvested and analyzed by microcomputed tomography and histology. RESULTS: Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation
Tae-Woo Kim and Woo-Beom Ahn contributed equally to this work as first authors.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13770-020-00257-5) contains supplementary material, which is available to authorized users. & Hyon-Seok Jang [email protected] 1
2
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Department of Dentistry, Graduate School of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea e-Well Dental Hospital, Suite #214, Daebang B/D, Shindaebang-dong, Dongjak-gu, Seoul 07056, Republic of Korea Laboratory Animal Center, Osong Medical Innovation Foundation, 123 Osongsaengmyeong-ro, Osong-eup, Heungdeok-gu, Cheonju-si, Chungbuk 28160, Republic of Korea
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Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 31116, Republic of Korea
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Department of Nanobiomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 31116, Republic of Korea
6
UIC Regenerative Medicine Research
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