title: Function of Platelet-Induced Epithelial Attachment at Titanium Surfaces Inhibits Microbial Colonization.
abstract: The aim of this study was to evaluate the barrier function of platelet-induced epithelial sheets on titanium surfaces. The lack of functional peri-implant epithelial sealing with basal lamina (BL) attachment at the interface of the implant and the adjacent epithelium allows for bacterial invasion, which may lead to peri-implantitis. Although various approaches have been reported to combat bacterial infection by surface modifications to titanium, none of these have been successful in a clinical application. In our previous study, surface modification with protease-activated receptor 4-activating peptide (PAR4-AP), which induced platelet activation and aggregation, was successful in demonstrating epithelial attachment via BL and epithelial sheet formation on the titanium surface. We hypothesized that the platelet-induced epithelial sheet on PAR4-AP-modified titanium surfaces would reduce bacterial attachment, penetration, and invasion. Titanium surface was modified with PAR4-AP and incubated with platelet-rich plasma (PRP). The aggregated platelets released collagen IV, a critical BL component, onto the PAR4-AP-modified titanium surface. Then, human gingival epithelial cells were seeded on the modified titanium surface and formed epithelial sheets. Green fluorescent protein (GFP)-expressing Escherichia coli was cultured onto PAR4-AP-modified titanium with and without epithelial sheet formation. While Escherichia coli accumulated densely onto the PAR4-AP titanium lacking epithelial sheet, few Escherichia coli were observed on the epithelial sheet on the PAR4-AP surface. No bacterial invasion into the interface of the epithelial sheet and the titanium surface was observed. These in vitro results indicate the efficacy of a platelet-induced epithelial barrier that functions to prevent bacterial attachment, penetration, and invasion on PAR4-AP-modified titanium.
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.|2 Department of Adhesive Dentistry, The Nippon Dental University, Chiyoda-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Maeno
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.affiliation: 3 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Kim
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Da Silva
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nagai
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.|4 Department of Prosthodontics and Oral Implantology, Iwate Medical University, School of Dental Medicine, Morioka, Iwate, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: 2 Department of Adhesive Dentistry, The Nippon Dental University, Chiyoda-ku, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nara
authors.affiliation: 1 Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, MA, USA.|4 Department of Prosthodontics and Oral Implantology, Iwate Medical University, School of Dental Medicine, Morioka, Iwate, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kihara
authors.affiliation: 3 Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nagai
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D001792:Blood Platelets / Q000502:physiology*; D000044:Dental Abutments; D015921:Dental Implants; D003764:Dental Materials / Q000737:chemistry*; D004846:Epithelial Attachment; D004926:Escherichia coli; D006801:Humans; D066298:In Vitro Techniques; D057873:Peri-Implantitis / Q000209:etiology / Q000517:prevention & control*; D053657:Platelet-Rich Plasma; D018179:Receptors, Thrombin / Q000737:chemistry*; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*; D014945:Wound Healing
chemical_list: D015921:Dental Implants; D003764:Dental Materials; D018179:Receptors, Thrombin; D014025:Titanium; C112908:protease-activated receptor 4
keywords: basement membrane; biomaterial(s); dental abutment; dental implant(s); peri-implant infection(s); wound healing