TY - JOUR
T1 - Fibroblast migration and collagen deposition during dermal wound healing
T2 - Mathematical modelling and clinical implications
AU - McDougall, Steven
AU - Dallon, John
AU - Sherratt, Jonathan
AU - Maini, Philip
PY - 2006/6/15
Y1 - 2006/6/15
N2 - The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-ß levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants. © 2006 The Royal Society.
AB - The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-ß levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants. © 2006 The Royal Society.
KW - Alignment
KW - Chemoattractant
KW - Fibroblasts
KW - Scar tissue
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=33646509272&partnerID=8YFLogxK
U2 - 10.1098/rsta.2006.1773
DO - 10.1098/rsta.2006.1773
M3 - Article
SN - 1364-503X
VL - 364
SP - 1385
EP - 1405
JO - Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
JF - Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
IS - 1843
ER -