title: Fluorescence-based retention assays reveals sustained release of vascular endothelial growth factor from bone grafts.
abstract: The sustained release of growth factors following their implantation in vivo is essential for successful outcomes in bone tissue engineering. In this study, we evaluated the release kinetics and delivery efficacies of vascular endothelial growth factor (VEGF), a potent angiogenic growth factor, incorporated into calcium phosphate bone grafts (BGs). We evaluated the release profile of VEGF from BGs using a novel fluorescence-based retention assay, which revealed that VEGF loaded on BGs can be released in a sustained manner without an initial burst (near zero-order cumulative release) with a controlled release rate of 13.6% per week for up to 7 weeks. In contrast, an ELISA-based release assay showed VEGF to have an early burst-release profile for the first week. However, the biological activity of VEGF released from the BGs was preserved over the 7-week release period, which is consistent with the sustained-release profile observed in the fluorescence-based retention assay. Furthermore, the in vivo bone-forming action of the VEGF-loaded BGs was well demonstrated in a rat subcutaneous model. Taken together, the sustained release of VEGF loaded onto BGs was effective in stimulating proliferation, angiogenesis and osteogenesis, suggesting the ultimate value of VEGF-engineered BGs for bone tissue engineering.
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon, 400-712, Republic of Korea.
authors.forename: Wonmo
authors.initials: W
authors.lastname: Kang
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330-714, Republic of Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Ye-Rang
authors.initials: YR
authors.lastname: Yun
authors.affiliation: Department of Biomedical Chemistry College of Health and Biomedical Science, Konkuk University, Chung-Ju, 380-701, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330-714, Republic of Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330-714, Republic of Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 330-714, Republic of Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 330-714, Republic of Korea.|Department of Biomaterials Science School of Dentistry, Dankook University, Cheonan, 330-714, Republic of Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon, 400-712, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D016025:Bone Transplantation; D003001:Cloning, Molecular; D003692:Delayed-Action Preparations; D004926:Escherichia coli; D005453:Fluorescence; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020007:Implants, Experimental; D007700:Kinetics; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D003692:Delayed-Action Preparations; D042461:Vascular Endothelial Growth Factor A
keywords: bone grafts; bone-forming action; fluorescence-based retention assay; human umbilical vein endothelial cells; rat subcutaneous model; vascular endothelial growth factor