title: Doxycycline-loaded coaxial nanofiber coating of titanium implants enhances osseointegration and inhibits Staphylococcus aureus infection.
abstract: Few studies have been reported that focus on developing implant surface nanofiber (NF) coating to prevent infection and enhance osseointegration by local drug release. In this study, coaxial doxycycline (Doxy)-doped polycaprolactone/polyvinyl alcohol (PCL/PVA) NFs were directly deposited on a titanium (Ti) implant surface during electrospinning. The interaction of loaded Doxy with both PVA and PCL NFs was characterized by Raman spectroscopy. The bonding strength of Doxy-doped NF coating on Ti implants was confirmed by a stand single-pass scratch test. The improved implant osseointegration by PCL/PVA NF coatings in vivo was confirmed by scanning electron microscopy, histomorphometry and micro computed tomography (μCT) at 2, 4 and 8 weeks after implantation. The bone contact surface (%) changes of the NF coating group (80%) is significantly higher than that of the no NF group (<5%, p < 0.05). Finally, we demonstrated that a Doxy-doped NF coating effectively inhibited bacterial infection and enhanced osseointegration in an infected (Staphylococcus aureus) tibia implantation rat model. Doxy released from NF coating inhibited bacterial growth up to 8 weeks in vivo. The maximal push-in force of the Doxy-NF coating (38 N) is much higher than that of the NF coating group (6.5 N) 8 weeks after implantation (p < 0.05), which was further confirmed by quantitative histological analysis and μCT. These findings indicate that coaxial PCL/PVA NF coating doped with Doxy and/or other drugs have great potential in enhancing implant osseointegration and preventing infection.
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, MI, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Joseph
authors.initials: J
authors.lastname: Seta
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Christopher
authors.initials: C
authors.lastname: Bergum
authors.forename: Zhubin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Praveen
authors.initials: P
authors.lastname: Kanneganti
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Kast
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Auner
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.forename: David C
authors.initials: DC
authors.lastname: Markel
authors.forename: Weiping
authors.initials: W
authors.lastname: Ren
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D004318:Doxycycline / Q000737:chemistry / Q000494:pharmacology*; D057139:Nanofibers; D016348:Osseointegration / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D019736:Prostheses and Implants; D051381:Rats; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects*; D013977:Tibia / Q000502:physiology*; D014025:Titanium / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D011142:Polyvinyl Alcohol; D014025:Titanium; D004318:Doxycycline