Development of a novel murine delayed secondary fracture healing in vivo model using periosteal cauterization

Ina Groengroeft, Sandra Wissing, Dennis M. Meesters, Martijn Poeze, Romano Matthys-Mark, Keita Ito, Stephan Zeiter*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction Delayed union and nonunion development remain a major clinical problematic complication during fracture healing, with partially unclear pathophysiology. Incidences range from 5 to 40% in high-risk patients, such as patients with periosteal damage. The periosteum is essential in adequate fracture healing, especially during soft callus formation. In this study, we hypothesize that inducing periosteal damage in a murine bone healing model will result in a novel delayed union model. Materials and methods A mid-shaft femoral non-critically sized osteotomy was created in skeletally mature C57BL/6 mice and stabilized with a bridging plate. In half of the mice, a thin band of periosteum adjacent to the osteotomy was cauterized. Over 42 days of healing, radiographic, biomechanical, micro-computed tomography and histological analysis was performed to assess the degree of fracture healing. Results Analysis showed complete secondary fracture healing in the control group without periosteal injury. Whereas the periosteal injury group demonstrated less than half as much maximum callus volume (p <0.05) and bridging, recovery of stiffness and temporal expression of callus growth and remodelling was delayed by 7-15 days. Conclusion This paper introduces a novel mouse model of delayed union without a critically sized defect and with standardized biomechanical conditions, which enables further investigation into the molecular biological, biomechanical, and biochemical processes involved in (delayed) fracture healing and nonunion development. This model provides a continuum between normal fracture healing and the development of nonunions.

Original languageEnglish
Pages (from-to)1743-1753
Number of pages11
JournalArchives of Orthopaedic and Trauma Surgery
Issue number12
Publication statusPublished - Dec 2019


  • Fracture healing
  • Delayed union
  • Endochondral ossification
  • Mice
  • CELL


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