Overview
Topic status: We're looking for students to study this topic.
Fracture healing is a complex interplay of both mechanically- and biologically-dependent tissue regeneration [1]. Much is still unknown regarding the relationship between cellular and mechanical factors in the fracture healing response and a reliable small animal model in which the mechanical environment can be controlled has not yet been resolved [2, 3].
The possibility of targeted additions or deletions from the mouse genome provides a powerful analysis tool for the study of the molecular biology of normal biological processes and diseases. Unfortunately, no single fracture model has emerged as a standard model, which would allow researchers from different laboratories to compare their findings much more readily and reliably.
Furthermore, the choice for fracture fixation in mice has so far been limited to external fixators [2] and intramedullary pins, which do not clearly define the biomechanics of the fracture fixation and are often very heavy and bulky compared to the weight and size of the experimental animal.
Therefore, the AO Foundation (Association for the study of internal fixation) in Switzerland has developed a new fracture and fixation system for mouse femora (MouseFix), which enables the researcher to perform the steps required to produce an osteotomy, stabilised by a rigid or flexible fracture fixation plate, in a highly standardised and reproducible fashion.
Furthermore, recent innovations in the design of fracture fixation plates for humans have been taken into account in the development of this system. The amount of interfragmentary movement is controlled by the use of rigid or flexible fixation plates. The amount of movement in fracture healing has been shown to affect the form of ossification (intramembranous or endochondral) and the size of the callus used to repair the fractured site.
This project aims to validate the use of the MouseFix plate system as a standardised and reproducible fracture model in the mouse femur to be used as a test platform to investigate the complex biological and mechanical interactions of fracture healing. Furthermore the effect of fixation screws and periosteal stripping will be explored.
Project Hypotheses: That periosteal stripping alone will provide sufficient stimulus for the formation of periosteal callus. Secondly, that intramembranous bone formation will be activated at the sites of screw placement within an internal fixation plate system.
Approaches: Animal surgery will be performed by placing rigid and flexible internal fixation plates to the femur of the mice. Bone histology will be performed on the right (periosteal stripped femur) and left (internal fixation plate without osteotomy) femora of mice sacrificed 4, 7 and 14 days. Photomicrographs of transverse serial sections will be compiled to produce 3D computer reconstructions of each bone using principles of tissue contrast; distribution of cartilaginous, bone and fibrous tissue will be analysed across the fracture gap; qualitative and quantitative aspects of tissue healing will be compared between animals stabilised by the rigid- and flexible-plate at each timepoint.
References:Claes, L., K. Eckert-Hubner, and P. Augat, The effect of mechanical stability on local vascularization and tissue differentiation in callus healing. J Orthop Res, 2002. (5): p. 1099-105.
- Thompson, Z., et al., A model for intramembranous ossification during fracture healing. J Orthop Res, 2002. (5): p. 1091-8.
- Le, A.X., et al., Molecular aspects of healing in stabilized and non-stabilized fractures. J Orthop Res, 2001. 19(1): p. 78-84.
- Study level
- Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
- Please contact the supervisor.
Dr Laura Gregory
