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 Jang7. 1. Department of Dentistry, Graduate School of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. 2. e-Well Dental Hospital, Suite #214, Daebang B/D, Shindaebang-dong, Dongjak-gu, Seoul, 07056, Republic of Korea. 3. Laboratory Animal Center, Osong Medical Innovation Foundation, 123 Osongsaengmyeong-ro, Osong-eup, Heungdeok-gu, Cheonju-si, Chungbuk, 28160, Republic of Korea. 4. Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam, 31116, Republic of Korea. 5. 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 Institute, Universitat Internacional de Catalunya, Carrer de la Immaculada 22, 08017, Barcelona, Spain. 7. Department of Dentistry, Graduate School of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. omfs119@korea.ac.kr.
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.
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.
Entities:
Keywords:
BMP-2; Bone regeneration; Drug carriers; Drug delivery system; VEGF
Authors: Davide Confalonieri; Margherita La Marca; Elisabeth Marianna Wilhelmina Maria van Dongen; Heike Walles; Franziska Ehlicke Journal: Tissue Eng Part A Date: 2017-07-11 Impact factor: 3.845