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Combined Delivery of Two Different Bioactive Factors Incorporated in Hydroxyapatite Microcarrier for Bone Regeneration

Tissue Engineering and Regenerative Medicine 2020년 17권 5호 p.607 ~ 624
김태우, 안우범, 김중민, 김중현, 김태현, Perez Roman A., 장현석,
소속 상세정보
김태우 ( Kim Tae-Woo ) - Korea University Graduate School of Medicine Department of Dentistry
안우범 ( Ahn Woo-Beom ) - Korea University Graduate School of Medicine Department of Dentistry
김중민 ( Kim Joong-Min ) - Korea University Graduate School of Medicine Department of Dentistry
김중현 ( Kim Joong-Hyun ) - Dankook University Institute of Tissue Regeneration Engineering
김태현 ( Kim Tae-Hyun ) - Dankook University Institute of Tissue Regeneration Engineering
 ( Perez Roman A. ) - Dankook University Institute of Tissue Regeneration Engineering
장현석 ( Jang Hyon-Seok ) - Korea University Graduate School of Medicine Department of Dentistry

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 (α-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 micro-computed 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 when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential.

Conclusion: We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability.

키워드

Drug carriers; BMP-2; VEGF; Drug delivery system; Bone regeneration

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