Matrix orientation plays a crucial role in determining the severity of scar tissue after dermal wounding. We have developed a multiscale modelling framework which allows us to examine the interaction of many of the factors involved in orientation and alignment. Briefly, the model considers a fibrin clot into which cells (modelled as discrete objects) move, degrading the clot and laying down collagen. The fibrin and the collagen matrix are modelled as continuous vector fields whose direction and length represent, respectively, the predominant orientation of fibres and their density. We have shown that this model predicts patterns of alignment on a macroscopic length scale that are lost in a continuum model of cell population and have used the model to investigate several factors which influence the alignment of collagen. Specifically, we related the model to current anti-scarring therapies using Transforming Growth Factor β (TGF-β). Using our model, we were able to tease out which of the many behavioural changes induced by TGF-β were the crucial factors influencing alignment, and hence scarring. This work was carried out in collaboration with mathematical colleagues Professor Jonathan A. Sherratt (Heriot-Watt University, Edinburgh) and Dr John Dallon (Brigham Young University, USA) and experimental colleague Professor Mark J. Ferguson, CBE (Faculty of Life Sciences, University of Manchester, Renovo Ltd). Intriguingly, many of the model predictions appear to hold true and we are presently investigating, in collaboration with the Ferguson laboratory, ways to verify the other model predictions before using the model to potentially aid in drug design for better healing.
Please contact Professor Philip K. Maini for more details.
Key references in this area
- P. Verhaegen, J. van Marle, A. Kuehne, H. Schouten, E. A. Gaffney, P. K. Maini and P. van Zuijlen (2012). Collagen bundle morphometry in skin and scar tissue: a novel distance mapping method provides superior measurements compared to Fourier analysis. J. Microscopy 245:82-89 (eprints)
- S. McDougall, J. Dallon, J. A. Sherratt and P. K. Maini (2006). Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications. Phil. Trans. Roy. Soc. A 364:1385-1405. (eprints)
- P. K. Maini, D. S. L. McElwain and S. Leavesley (2004). Travelling waves in a wound healing assay. Appl. Math. Lett. 17:575-580. (eprints)