title: Immobilization of alendronate on titanium via its different functional groups and the subsequent effects on cell functions.
abstract: Immobilization of alendronate on orthopedic implants offers the possibility of enhancing osteogenesis without potentially adverse effects associated with systemic administration of this drug. In this work, alendronate was immobilized on titanium (Ti) via either its phosphate (Method 1) or amino (Method 2) groups, and responses of osteoblasts and human mesenchymal stem cells (hMSCs) on these surfaces were investigated. These modified substrates have similar surface roughness and are negatively charged. With similar amounts of immobilized alendronate, these two types of modified substrates showed comparable osteogenic stimulating effects in enhancing osteoblasts' alkaline phosphatase (ALP) activity and calcium deposition for the first 10days. However, alendronate immobilized via its phosphate groups was less stable, and gradually leached into the medium. As a result, its stimulating effect on osteoblast differentiation diminished with time. On the other hand, alendronate immobilized via its amino group stimulated osteoblast differentiation over 21days, and with 1655ng/cm2of immobilized alendronate on the Ti substrate, calcium deposition by osteoblasts and hMSCs increased by 30% and 69%, respectively, compared to pristine Ti after 21days. The expressions of runt-related transcription factor 2, osterix, osteopontin and osteocalcin in hMSCs cultured on this substrate were monitored. The up-regulation of these genes is postulated to play a role in the acceleration of osteogenic differentiation of hMSCs cultured on the alendronate-modified substrate over those on pristine Ti.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore. Electronic address: chenkg@nus.edu.sg.
authors.forename: Koon Gee
authors.initials: KG
authors.lastname: Neoh
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 117576, Singapore.
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
mesh_terms: D000327:Adsorption; D019386:Alendronate / Q000737:chemistry* / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000588:Amines / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010710:Phosphates / Q000737:chemistry; D000076182:Sp7 Transcription Factor; D055672:Static Electricity; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000588:Amines; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D050659:Core Binding Factor Alpha 1 Subunit; D010710:Phosphates; C493709:RUNX2 protein, human; C506895:SPP1 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D014025:Titanium; D000469:Alkaline Phosphatase; D002118:Calcium; D019386:Alendronate
keywords: Alendronate; Bisphosphonate; Gene expression; Osteoblast; Stem cell; Surface immobilization; Titanium