title: Structural and biomechanical responses of osseous healing: a novel murine nonunion model.
abstract: BACKGROUND
  Understanding the biological mechanisms of why certain fractures are at risk for delayed healing or nonunion requires translational animal models that take advantage of transgenic and other genetic manipulation technologies. Reliable murine nonunion models can be an important tool to understand the biology of nonunion. In this study, we report the results of a recently established model for creating critical defects that lead to atrophic nonunions based on a unique fracture fixation technique.
  
  
  METHODS
  Subcritical (0.6 mm long) and critical (1.6 mm long) defects were created in femurs of 10-week-old double transgenic (Col1/Col2) mice and stabilized using a custom-designed plate and four screws. Four groups were used: normal, sham, subcritical, and critical. Histology (n = 3 for each group) was analyzed at 2 and 5 weeks, and micro-computed tomography (μCT) and torsional biomechanics (n = 12 for each group) were analyzed at 5 weeks.
  
  
  RESULTS
  Subcritical defects showed healing at 2 weeks and were completely healed by 5 weeks, with biomechanical properties not significantly different from normal controls. However, critical defects showed no healing by histology or μCT. These nonunion fractures also displayed no torsional stiffness or strength in 10 of 12 cases.
  
  
  CONCLUSIONS
  Our murine fracture model creates reproducible and reliable nonunions and can serve as an ideal platform for studying molecular pathways to contrast healing versus nonhealing events and for evaluating innovative therapeutic approaches to promote healing of a challenging osseous injury.
authors.affiliation: Biomedical Engineering Program, School of Energy, Environmental and Biological and Medical Engineering, University of Cincinnati, 2901 Woodside Dr, Cincinnati, OH, 45221-0048, USA, aditya.chaubey@gmail.com.
authors.forename: Aditya
authors.initials: A
authors.lastname: Chaubey
authors.forename: Brian
authors.initials: B
authors.lastname: Grawe
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meganck
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Dyment
authors.forename: Jason
authors.initials: J
authors.lastname: Inzana
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Camille
authors.initials: C
authors.lastname: Connolley
authors.forename: Hani
authors.initials: H
authors.lastname: Awad
authors.forename: David
authors.initials: D
authors.lastname: Rowe
authors.forename: Keith
authors.initials: K
authors.lastname: Kenter
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldstein
authors.forename: David
authors.initials: D
authors.lastname: Butler
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D001860:Bone Plates; D001863:Bone Screws; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery*; D017102:Fracture Healing / Q000502:physiology*; D005599:Fractures, Ununited / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery*; D016268:Internal Fixators; D008297:Male; D051379:Mice; D011897:Random Allocation; D019415:Torque; D055114:X-Ray Microtomography