title: Strontium (Sr) and silver (Ag) loaded nanotubular structures with combined osteoinductive and antimicrobial activities.
abstract: Two frequent problems are associated with the titanium surfaces of bone/dental implants: lack of native tissue integration and associated infection. These problems have prompted a significant body of research regarding the modification of these surfaces. The present study describes a hydrothermal treatment for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures with different tube diameters on titanium surfaces. The Sr loading from a Sr(OH)2 solution was regulated by the size of the inner diameter of the titanium nanotubes (NT) (30nm or 80nm, formed at 10V or 40V, respectively). The quantity of Ag was adjusted by immersing the samples in 1.5 or 2.0M AgNO3 solutions. Sr and Ag were released in a controllable and prolonged matter from the NT-Ag.Sr samples, with negligible cytotoxicity. Prominent antibacterial activity was observed due to the release of Ag. Sr incorporation enhanced the initial cell adhesion, migration, and proliferation of preosteoblast MC3T3-E1 cells. Sr release also up-regulated the expression of osteogenic genes and induced mineralization, as suggested by the presence of more mineralized calcium nodules in cells cultured on NT-Ag.Sr surfaces. In vivo experiments showed that the Sr-loaded samples accelerated the formation of new bone in both osteoporosis and bone defect models, as confirmed by X-ray, Micro-CT evaluation, and histomorphometric analysis of rats implanted with NT-Ag.Sr samples. The antibacterial activity and outstanding osteogenic properties of NT-Ag.Sr samples highlight their excellent potential for use in clinical applications.
  
  
  CONCLUSIONS
  Two frequent problems associated with Ti surfaces, widely used in orthopedic and dental arenas, are their lack of native tissue integration and risk of infection. We describe a novel approach for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures on titanium surfaces. A relevant aspect of this work is the demonstration of long-lasting and controllable Ag release, leading to excellent antibacterial and anti-adherent properties against methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria such as Escherichia coli. The extended release of Sr accelerates the filling of bone defects by improving the repair of damaged cortical bone and increasing trabecular bone microarchitecture. Our results highlight the potential of Sr and Ag loaded nanotubular structures for use in clinical applications.
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Hanfeng
authors.initials: H
authors.lastname: Guan
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Ave. Eugenio Garza Sada 2501 Sur Col. Tecnológico, CP 64849 Monterrey, Nuevo León, Mexico; Microsystems Technologies Laboratories, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.
authors.forename: Mario Moisés
authors.initials: MM
authors.lastname: Alvarez
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Gao
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Kaifu
authors.initials: K
authors.lastname: Huo
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Jiangwen
authors.initials: J
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Refractories and Metallurgy, School of Materials and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China. Electronic address: fujijiang@wust.edu.cn.
authors.forename: Jijiang
authors.initials: J
authors.lastname: Fu
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Microsystems Technologies Laboratories, Massachusetts Institute of Technology, Cambridge 02139, MA, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, MA, USA; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea; Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China. Electronic address: lifengmd@hust.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D004926:Escherichia coli / Q000187:drug effects; D005786:Gene Expression Regulation; D053768:Metal Nanoparticles / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D043942:Nanotubes / Q000737:chemistry; D010012:Osteogenesis; D010024:Osteoporosis / Q000628:therapy; D051381:Rats; D012834:Silver / Q000737:chemistry*; D013324:Strontium / Q000737:chemistry*; D013499:Surface Properties; D023822:Tissue Engineering; D014025:Titanium / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D000900:Anti-Bacterial Agents; D012834:Silver; D014025:Titanium; D013324:Strontium
keywords: Antibacterial; Nanotubular structures; Osteogenic; Silver; Strontium; Titanium