Advances in the Establishment of Defined Mouse Models for the Study of Fracture Healing and Bone Regeneration

Abstract

The availability of a broad spectrum of antibodies and gene-targeted animals caused an increasing interest in mouse models for the study of molecular mechanisms of fracture healing and bone regeneration. In most murine fracture models, the tibia or the femur is fractured using a 3-point bending device (closed models) or is osteotomized using an open surgical approach (open models). For fracture studies in mice, the tibia has to be considered less appropriate compared with the femur because the stabilization of the fracture is more difficult due to its triangular, distally declining caliber and its bowed longitudinal axis. Biomechanical factors critically influence the bone healing process. Thus, the use of stable osteosynthesis techniques is also of interest in murine fracture models. To achieve stable fixation, several biomechanically standardized implants have recently been introduced, including a locking nail and an intramedullary compression screw. Other implants, such as a pin-clip, an external fixator, and a locking plate, additionally allow the stabilization of fractures with distinct gap sizes. This enables the study of healing of critical size defects and nonunions. The use of these implants further allows a rigid fixation of fractures in bridle bones, which is essential for fracture studies in animals suffering from metabolic bone diseases like osteoporosis. In general, the analysis of bone healing in these models includes different imaging techniques and histologic, immunohistochemical, biomechanical, and molecular methods. To evaluate the impact of different osteosynthesis techniques on physical activity and rehabilitation, gait analysis may additionally be performed. By this, the gait of the animals can be visualized and quantitatively analyzed using modified running wheels and dynamic high-resolution radiography systems. Taken together, a variety of different murine femur fracture models have become available, providing defined biomechanical conditions for fracture research. The use of these mouse models may now allow studying the influence of fracture stabilization techniques on molecular mechanisms of bone healing.

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

“…These findings confirmed previous results using this model (Garcia et al, 2008a;Garcia et al, 2008b;Garcia et al, 2012;Holstein et al, 2009;Holstein et al, 2011;Histing et al, 2009;Histing et al, 2011). In contrast, MCM + BMP treatment induced osseous bridging already after 2 weeks.…”

Establishment of a Segmental Femoral Critical-size Defect Model in Mice Stabilized by Plate Osteosynthesis

“…This outcome contrasts also the results reported when either an external fixator or an intramedullary nail were used 4,5,[17][18][19][20][21][22][23][24] . For the external fixators potential disadvantages include: variability in stiffness, infections of the pins tracts, loosening of the pins, potentials injuries due to the pins and the weight of the materials (4 to 20% of the mouse body weight).…”

Pseudofracture: An Acute Peripheral Tissue Trauma Model

“…[16][17][18][19][20][21] The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. [22][23][24][25][26][27][28][29][30] This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone.…”