A multiscale hybrid mathematical model of epidermal-dermal interactions during skin wound healing

Experimental Dermatology
Yangyang WangQing Nie

Abstract

Following injury, skin activates a complex wound healing programme. While cellular and signalling mechanisms of wound repair have been extensively studied, the principles of epidermal-dermal interactions and their effects on wound healing outcomes are only partially understood. To gain new insight into the effects of epidermal-dermal interactions, we developed a multiscale, hybrid mathematical model of skin wound healing. The model takes into consideration interactions between epidermis and dermis across the basement membrane via diffusible signals, defined as activator and inhibitor. Simulations revealed that epidermal-dermal interactions are critical for proper extracellular matrix deposition in the dermis, suggesting these signals may influence how wound scars form. Our model makes several theoretical predictions. First, basal levels of epidermal activator and inhibitor help to maintain dermis in a steady state, whereas their absence results in a raised, scar-like dermal phenotype. Second, wound-triggered increase in activator and inhibitor production by basal epidermal cells, coupled with fast re-epithelialization kinetics, reduces dermal scar size. Third, high-density fibrin clot leads to a raised, hypertrophic scar phenot...Continue Reading

References

Jul 23, 1990·Proceedings. Biological Sciences·J A Sherratt, J D Murray
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·A B RobertsJ H Kehrl
Mar 1, 1997·The Journal of Investigative Dermatology·H MurataV Falanga
Jan 1, 1997·The International Journal of Biochemistry & Cell Biology·S O'Kane, M W Ferguson
Jul 9, 1998·Plastic and Reconstructive Surgery·W L Garner
Mar 29, 2002·Journal of Cellular Physiology·Vincent FalangaTatyana Yufit
May 4, 2002·Nature Reviews. Molecular Cell Biology·James J TomasekRobert A Brown
Jun 25, 2003·Journal of Dental Research·R HosokawaM Ohishi
Feb 10, 2004·Frontiers in Bioscience : a Journal and Virtual Library·Robert F Diegelmann, Melissa C Evans
Aug 6, 2004·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Mark W J Ferguson, Sharon O'Kane
Oct 29, 2004·Plastic and Reconstructive Surgery·Barry L EppleyJoel Higgins
Feb 15, 2007·The Journal of Investigative Dermatology·Sabine A EmingJeffrey M Davidson
Apr 17, 2007·The Journal of Investigative Dermatology·Sabine WernerHans Smola
Mar 13, 2008·Science Signaling·Rebecca G Wells, Dennis E Discher
May 16, 2008·Nature·Geoffrey C GurtnerMichael T Longaker
Jul 16, 2008·Journal of Mathematical Biology·T Hillen, K J Painter
Jan 9, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Stephan BarrientosMarjana Tomic-Canic
Mar 28, 2009·Journal of the Royal Society, Interface·B D CummingZ Upton
Jul 1, 2005·Mathematical Biosciences and Engineering : MBE·T J Newman
Nov 11, 2011·Journal of Mathematical Biology·F J Vermolen, E Javierre
Mar 15, 2012·Nature Communications·Alfiya AkhmetshinaJörg H W Distler
May 25, 2012·The Journal of Investigative Dermatology·Emily J Hamburg, Radhika P Atit
May 26, 2012·Proceedings. Biological Sciences·Shakti N MenonD L Sean McElwain
Mar 16, 2013·Bulletin of Mathematical Biology·Josephine T Daub, Roeland M H Merks
Mar 19, 2013·Journal of Tissue Engineering and Regenerative Medicine·Eduardo AnituaGorka Orive
Jun 4, 2013·Nature Medicine·Denise GayGeorge Cotsarelis
Aug 21, 2013·Journal of Dermatological Science·Nicholas S GreavesArdeshir Bayat
Feb 15, 2014·Advances in Wound Care·Kenneth W FinnsonAnie Philip
Jul 18, 2014·Advances in Wound Care·Irena PastarMarjana Tomic-Canic
Nov 22, 2014·Science·Bryan K SunPaul A Khavari
Dec 5, 2014·Science Translational Medicine·Sabine A EmingMarjana Tomic-Canic
Mar 19, 2015·Advances in Wound Care·Meilang Xue, Christopher J Jackson
May 29, 2015·Genes & Development·Tomoaki IwayamaLorin E Olson
Aug 9, 2015·Cell Stem Cell·Amanda M NelsonLuis A Garza
Aug 12, 2016·Experimental Dermatology·Sun Hyung Kwon, Geoffrey C Gurtner
Jan 7, 2017·Science·Maksim V PlikusGeorge Cotsarelis
Feb 3, 2018·The Journal of Investigative Dermatology·Christina PhilippeosFiona M Watt
Feb 3, 2018·Advances in Wound Care·Clement D MarshallMichael T Longaker
Feb 27, 2018·PLoS Computational Biology·Huijing DuQing Nie

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Citations

Jul 31, 2019·Nature Cell Biology·Qing Nie, Maksim V Plikus
Dec 23, 2020·Experimental Dermatology·Maksim V Plikus, Thomas Krieg

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