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Abstract
IntroductionDelayed 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 methodsA 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.ResultsAnalysis 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.ConclusionThis 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.
Highlights
Delayed union and nonunion development remain a major clinical problematic complication during fracture healing, with partially unclear pathophysiology
The aim of the current project was to develop an in vivo murine model for delayed union development, as an intermediary between normal fracture healing and the development of nonunions, for future possibilities in biochemical and molecular research to investigate enhanced and deficient bone healing processes
Results demonstrated that the fracture gap obtained after a standardized osteotomy reduced with semi-rigid internal plate-screw osteosynthesis and combined with periosteal injury prolonged the healing period for 7–14 days, with callus formation volumes after 42 days of fracture healing which were comparable with callus after 21–28 days in the control group
Summary
Delayed union and nonunion development remain a major clinical problematic complication during fracture healing, with partially unclear pathophysiology. 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. During the last decade(s), in vivo research in rodents has resulted in a wide range of different animal models for fracture healing and compromised healing resulting in delayed union and nonunion development [4, 5] These models have to be standardized and need to mimic the human clinical situation as close as possible. Availability of knockout mice and senescence altered mice allows a broad spectrum of molecular biology-based investigations [20] into developmental biological issues such as bone and cartilage formation [9, 12, 17] in combination with these different healing models
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