title: Chitosan/siCkip-1 biofunctionalized titanium implant for improved osseointegration in the osteoporotic condition.
abstract: Biofunctionalization with siRNA targeting the key negative modulators of bone turnover involved in the molecular mechanism of osteoporosis, such as casein kinase-2 interacting protein-1 (Ckip-1), may lead to enhanced Ti osseointegration in the osteoporotic condition. In this study, even siRNA loading was accomplished by the thermal alkali (TA) treatment to make the Ti ultrahydrophilic and negatively charged to facilitate the physical adsorption of the positively charged CS/siR complex, designated as TA-CS/siR. The intracellular uptake of the CS/siR complex and the gene knockdown efficiency were assessed with bone marrow mesenchymal stem cells (MSCs) as well as the green fluorescent protein (GFP) expressing H1299 cells. In vitro osteogenic activity of TA-CS/siCkip-1 targeting Ckip-1 was assessed with MSCs. In vivo osseointegration of TA-CS/siCkip-1 was assessed in the osteoporotic rat model. TA-CS/siR showed excellent siRNA delivery efficiency and gene silencing effect. TA-CS/siCkip-1 significantly improved the in vitro osteogenic differentiation of MSCs in terms of the enhanced alkaline phosphatase and collagen product and extracellular matrix mineralization, and led to dramatically enhanced in vivo osseointegration in the osteoporostic rat model, showing promising clinical potential for the osteoporotic condition application. TA-CS/siR may constitute a general approach for developing the advanced Ti implants targeting specific molecular mechanism.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, 401 Military Hospital, Qingdao 266071, China.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Song
authors.affiliation: State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, the Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, the Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Ran
authors.initials: R
authors.lastname: An
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, the Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an 710032, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D049109:Cell Proliferation; D048271:Chitosan; D004195:Disease Models, Animal; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D016348:Osseointegration; D010012:Osteogenesis; D010024:Osteoporosis / Q000175:diagnosis / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D013997:Time Factors; D014025:Titanium; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human; D034741:RNA, Small Interfering; D048271:Chitosan; D014025:Titanium