title: Osseointegration: hierarchical designing encompassing the macrometer, micrometer, and nanometer length scales.
abstract: OBJECTIVE
  Osseointegration has been a proven concept in implant dentistry and orthopedics for decades. Substantial efforts for engineering implants for reduced treatment time frames have focused on micrometer and most recently on nanometer length scale alterations with negligible attention devoted to the effect of both macrometer design alterations and surgical instrumentation on osseointegration. This manuscript revisits osseointegration addressing the individual and combined role of alterations on the macrometer, micrometer, and nanometer length scales on the basis of cell culture, preclinical in vivo studies, and clinical evidence.
  
  
  METHODS
  A critical appraisal of the literature was performed regarding the impact of dental implant designing on osseointegration. Results from studies with different methodological approaches and the commonly observed inconsistencies are discussed.
  
  
  RESULTS
  It is a consensus that implant surface topographical and chemical alterations can hasten osseointegration. However, the tailored combination between multiple length scale design parameters that provides maximal host response is yet to be determined.
  
  
  CONCLUSIONS
  In spite of the overabundant literature on osseointegration, a proportional inconsistency in findings hitherto encountered warrants a call for appropriate multivariable study designing to ensure that adequate data collection will enable osseointegration maximization and/or optimization, which will possibly lead to the engineering of endosteal implant designs that can be immediately placed/loaded regardless of patient dependent conditions.
authors.affiliation: Department of Biomaterials and Biomimetics, New York University, 345 East 24th Street, Room 804s, New York, NY 10010, United States; Director for Research, Department of Periodontology and Implant Dentistry, New York University, United States; Affiliated Faculty, Division of Engineering, New York University Abu Dhabi, United Arab Emirates. Electronic address: pgcoelho@nyu.edu.
authors.forename: Paulo G
authors.initials: PG
authors.lastname: Coelho
authors.affiliation: Department of Prosthodontics, Faculty of Odontology, Malmö University, SE 205 06 Malmö, Sweden. Electronic address: ryo.jimbo@mah.se.
authors.forename: Ryo
authors.initials: R
authors.lastname: Jimbo
authors.affiliation: Department of Biomaterials and Biomimetics, New York University, 345 East 24th Street, Room 804s, New York, NY 10010, United States. Electronic address: nicktovar@gmail.com.
authors.forename: Nick
authors.initials: N
authors.lastname: Tovar
authors.affiliation: Department of Prosthodontics, University of São Paulo - Bauru College of Dentistry, Al. Otávio Pinheiro Brisola 9-75, 17.012.901 Bauru, SP, Brazil. Electronic address: estevamab@gmail.com.
authors.forename: Estevam A
authors.initials: EA
authors.lastname: Bonfante
mesh_terms: D003758:Dental Implantation, Endosseous / Q000379:methods*; D015921:Dental Implants; D017267:Dental Prosthesis Design; D017268:Dental Prosthesis Retention; D019232:Dental Restoration Failure; D006801:Humans; D016348:Osseointegration / Q000502:physiology*; D011788:Quality of Life
chemical_list: D015921:Dental Implants
keywords: Design; Macrogeometry; Osseointegration; Review; Surface