Rodent Models for the Study of Articular Fracture Healing

Abstract

The goal of this study was to document the healing time course and expression of ex vivo cell-based gene delivery in articular fracture models in the mouse and rat. Articular medial intercondylar femoral osteotomy was performed in the stifle (knee) joints of hairless immunocompetent mice and medial or lateral similar osteotomy was performed in athymic nude rats. Genetically modified cells expressing luciferase were delivered in a three-dimensional alginate matrix directly into the osteotomy site. Sensitivity of an in vivo imaging system to detect expression of luciferase was compared between rodents in this fracture model. Osteotomy healing was assessed using high-detail radiography, helical computed tomography (CT), high-field magnetic resonance imaging, and histology. The mouse model was less satisfactory because the small size of the murine femur made reliable assessment of fracture healing restricted to histopathology, and complications occurred in 11/24 mice (45.8%), most frequently transverse supracondylar femoral fracture postoperatively. Gene expression was inconsistently confirmed in mice in vivo for 11 days (p <. 003). In rats, high-detail radiography and CT were used to assess osteotomy healing. Magnetic resonance imaging (4.7 T) in rats could produce three-dimensional images that would permit assessment of bone and cartilage, but was time-consuming and expensive. In rats, the only surgical complication, transverse femoral fracture, was reduced from 83.3% with the medial osteotomy to 0% with a lateral osteotomy. In vivo imaging confirmed gene expression in the alginate/cell constructs in rats for at least 4 days (p <. 05). The nude rat model has the advantage of larger femora and the ability to implant xenograft cells. A lateral intercondylar osteotomy of the distal femur in the rat can be used to study the healing of articular fractures.

KEYWORDS:

• articular fracture
• knee
• mouse
• rat