Abstract
Aims An estimated 5–10% of fractures fail to heal adequately. Novel therapies in the treatment of problem fractures include the use of culture expanded cells. An animal model of delayed fracture union is required to parallel the clinical scenario so that variations in cell therapy techniques can be rapidly assessed.
Material and Methods A simple unilateral external fixator was designed for use in the rat. The fixator was applied following open osteotomy of the femur and a reproducible externally fixated femoral fracture model was established (n=41). Fracture union was assessed by digital radiography, histology and biomechanical strength testing (four point bending) at weeks 4, 6 and 8. Histological examination was also undertaken at day 4 and weeks 1 and 2. A delayed union in the fracture model was created by periosteal and endosteal stripping (n=14). Radiography and biomechanical strength testing were performed at week 8. The use of cell therapy was tested in the delayed union model. Osteogenic cells were culture expanded for 6 weeks before re-implantation. Reimplantation was facilitated by the use of a drill hole through the fracture site . Animals were randomized to one of three groups – i) drill hole & cells in a carrier ii) drill hole & carrier only iii) no drill hole, cells or carrier.
Results In the fracture model radiological and histological evidence of fracture union was apparent at week 6. Biomechanical testing showed a significant difference in load to failure and stiffness of the fracture between weeks 4 and 8 (p=0.009 and 0.008 respectively). There was also a significant difference in biomechanical properties between the fracture model and the delayed union model at week 8. Drilling with the injection of a carrier significantly improved the biomechanical properties (p=0.03) of a delayed union at week 14. Surprisingly this effect was negated by the introduction of cells.
Conclusion A fracture and delayed union model in the rat has been established for the testing of cell therapy. The application of cell therapy to a delayed union has been less advantageous in improving union than expected. This prompts the need for further work required in optimising cell culture techniques and cell delivery.
Correspondence should be addressed to Mr Carlos Wigderowitz, Honorary Secretary BORS, University Dept of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School, Dundee DD1 9SY.
None of the authors have received anything of value from a commercial or other party related directly or indirectly to the subject of the presentation
