title: Surface Modification of Titanium with BMP-2/GDF-5 by a Heparin Linker and Its Efficacy as a Dental Implant.
abstract: In this study, we prepared human bone morphogenetic protein-2 (hBMP-2)/human growth and differentiation factor-5 (hGDF-5)-coated titanium (Ti) disc and screw types for controlled release of the growth factors (GFs). The two growth factors were coated onto Ti with a smooth surface using their specific interaction with heparin, because they have heparin binding sites in their molecular structures. Efficacy of the two growth factor-coated Ti for enhancement of bone formation and osseointegration was compared to pristine Ti, and hBMP-2- and hGDF-5-coated Ti in vivo. The surface chemical composition, surface morphology, and wettability characteristics of the metal samples were determined by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurement, respectively. The initial burst of hBMP-2, hGDF-5, and their combination, occurred within one day of the release study, resulting in 12.5%, 4.5%, and 13.5%/3.2%, and then there was a sustained, even release of these two growth factors from the coated metal for 30 days. In vitro tests revealed that MC3T3-E1 cells cultured on the two growth factor-coated Ti had a higher proliferation rate and a higher activity for alkaline phosphatase (ALP), which led to a larger amount of calcium deposition and larger expressions of type I collagen (COL 1),ALP, and osteocalcin (OCN) mRNAs. In vivo animal tests using ten white New Zealand rabbits showed that the two growth factor-coated Ti enhanced bone formation and osseointegration at the interface between the implants and host bone. In addition, histological evaluation showed that bone remodeling, including bone formation by osteoblasts and bone resorption by osteoclasts, actively occurred between the two growth factor-coated Ti and host bone. Consequently, it is suggested that Ti surface modification with the combination of hBMP-2 and hGDF-5 for the two growth factor-coated Ti implants can improve the clinical properties of implants for orthopedic and dental applications.
authors.affiliation: Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. yangdh@catholic.ac.kr.
authors.forename: Dae Hyeok
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, College of Medicine, Kyung Hee University, Seoul 02454, Korea. msw@khnmc.or.kr.
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Moon
authors.affiliation: Department of Oral & Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong, Kyung Hee University, #892 Dongnam-ro, Gangdong-gu, Seoul 05278, Korea. verycutebear@hanmail.net.
authors.forename: Deok-Won
authors.initials: DW
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015921:Dental Implants; D005786:Gene Expression Regulation / Q000187:drug effects; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D056951:Photoelectron Spectroscopy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D015921:Dental Implants; D055428:Growth Differentiation Factor 5; D012333:RNA, Messenger; D014867:Water; D006493:Heparin; D014025:Titanium; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: bone formation; heparin; human bone morphogenetic protein-2; human growth and differentiation factor-5; osseointegration