Spatio-temporal Models of Lymphangiogenesis in Wound Healing.
Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: (1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case and (2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here, we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.
Department of Mathematics and Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, Scotland, UK. arianna.bianchi@ualberta.ca.|University of Alberta, 632 Central Academic Building, Edmonton, AB, T6G 2G1, Canada. arianna.bianchi@ualberta.ca.
Arianna
A
Bianchi
Department of Mathematics and Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, Scotland, UK.
Kevin J
KJ
Painter
Department of Mathematics and Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, Scotland, UK.
Jonathan A
JA
Sherratt
D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008196:Lymph / Q000502:physiology; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000502:physiology; D055641:Mathematical Concepts; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A
Interstitial flow; Lymphangiogenesis; Mathematical model; Wound healing