Development of an ischemic fracture healing model in mice

Maximilian M Menger; Janine Stutz; Sabrina Ehnert; Andreas K Nussler; Mika F Rollmann; Steven C Herath; Benedikt J Braun; Tim Pohlemann; Michael D Menger; Tina Histing

doi:10.2340/17453674.2022.2529

Authors

Maximilian M Menger Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen
Janine Stutz Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar; Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg/Saar
Sabrina Ehnert Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen; Department of Trauma and Reconstructive Surgery, BG Trauma Center Tübingen, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tübingen, Tübingen, Germany
Andreas K Nussler Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen; Department of Trauma and Reconstructive Surgery, BG Trauma Center Tübingen, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tübingen, Tübingen, Germany
Mika F Rollmann Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen
Steven C Herath Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen https://orcid.org/0000-0003-4213-8676
Benedikt J Braun Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen
Tim Pohlemann Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg/Saar
Michael D Menger Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar https://orcid.org/0000-0002-9670-7961
Tina Histing Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen

DOI:

https://doi.org/10.2340/17453674.2022.2529

Keywords:

Biomechanics, Blood vessels, Bone, Fractures

Abstract

Background and purpose: In fracture healing, ischemia caused by vascular injuries, chronic vascular diseases, and metabolic comorbidities is one of the major risk factors for delayed union and non-union formation. To gain novel insights into the molecular and cellular pathology of ischemic fracture healing, appropriate animal models are needed. Murine models are of particular interest, as they allow to study the molecular aspects of fracture healing due to the availability of both a large number of murine antibodies and gene-targeted animals. Thus, we present the development of an ischemic fracture healing model in mice.
Material and methods: After inducing a mild ischemia by double ligature of the deep femoral artery in CD-1 mice, the ipsilateral femur was fractured by a 3-point bending device and stabilized by screw osteosynthesis. In control animals, the femur was fractured and stabilized without the induction of ischemia. The femora were analyzed at 2 and 5 weeks after fracture healing by means of radiology, biomechanics, histology, and histomorphometry.
Results: The surgically induced ischemia delayed and impaired the process of fracture healing. This was indicated by a lower Goldberg score, decreased bending stiffness, and reduced bone callus formation in the ischemic animals when compared with the controls.
Interpretation: We introduce a novel ischemic femoral fracture healing model in mice, which is characterized by delayed bone healing. In future, the use of this model may allow both the elucidation of the molecular aspects of ischemic fracture healing and the study of novel treatment strategies.