Mathematical investigation of the interactions between the inflammatory response and mechanical aspects of dermal wound repair

Murphy, Kelly Elizabeth (2011) Mathematical investigation of the interactions between the inflammatory response and mechanical aspects of dermal wound repair. PhD thesis, Queensland University of Technology.

Abstract

Dermal wound repair involves complex interactions between cells, cytokines and mechanics to close injuries to the skin. In particular, we investigate the contribution of fibroblasts, myofibroblasts, TGFβ, collagen and local tissue mechanics to wound repair in the human dermis. We develop a morphoelastic model where a realistic representation of tissue mechanics is key, and a fibrocontractive model that involves a reasonable approximation to the true kinetics of the important bioactive species. We use each of these descriptions to elucidate the mechanisms that generate pathologies such as hypertrophic scars, contractures and keloids.

We find that for hypertrophic scar and contracture development, factors regulating the myofibroblast phenotype are critical, with heightened myofibroblast activation, reduced myofibroblast apoptosis or prolonged inflammation all predicted as mediators for scar hypertrophy and contractures. Prevention of these pathologies is predicted when myofibroblast apoptosis is induced, myofibroblast activation is blocked or TGFβ is neutralised.

To investigate keloid invasion, we develop a caricature representation of the fibrocontractive model and find that TGFβ spread is the driving factor behind keloid growth. Blocking activation of TGFβ is found to cause keloid regression. Thus, we recommend myofibroblasts and TGFβ as targets for clinicians when developing intervention strategies for prevention and cure of fibrotic scars.

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ID Code: 67907
Item Type: QUT Thesis (PhD)
Supervisor: McElwain, Sean & McCue, Scott
Keywords: apoptosis, biomechanics, continuum mechanics, contracture, dermal wound healing, fibroblast, hypertrophic scar, inflammation, keloid, mathematical biology, mathematical modelling, morphoelasticity, myofibroblast, therapy, transforming growth factor β, viscoelasticity, zero stress state
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > Mathematical Sciences
Institution: Queensland University of Technology
Deposited On: 27 Feb 2014 06:19
Last Modified: 27 Feb 2014 06:21

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