Defense Date

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Integrative Life Sciences

First Advisor

Tarynn M. Witten

Abstract

Dermal wound healing proliferative phase is a complicated physiological process in which many growth factors, cell types and matrix components participate. The process must be well coordinated to restore the structural and functional integrity of tissue injured. Many disorders interrupting healing process result in abnormal healing such as chronic wounds or excessive scarring. Mathematical modeling has been used to investigate many aspects of wound healing. Angiogenesis is pertinent for dermal wound healing since the cellular activities involved in tissue repair requires oxygen and nutrients to be delivered to the wound site. By using a hybrid agent-based model, we investigated the interactive dynamics of vasculature growth and collagen network growth. Our model further examine the effects of tissue oxygen tension (hypoxia, normoxia, hyperoxia) on healing process. Wound contraction is generally beneficial for the overall healing since it reduces the wound size thus reduces the chance to be infected. However, contraction going overboard may result in excessive scarring. Our model seeks to investigate the source of driving force during early and late stage of wound contraction. For the first time, skin is modeled as a fiber-reinforced anisotropic soft tissue. The effects of a dynamically orienting collagen matrix on the contraction process are thus shown. The simulation results of the model agree with the hypothesis that scar formation is the byproduct of collagen fiber synthesis and alignment in the presence of the tensile stress field generated by a wound contraction process. Multi-scale modeling is illuminating because it can help explain the phenomena at tissue level by the subcellular level events. We built a multi-scale model of general wound healing proliferative phase by embedding a TGFbeta pathway to each fibroblasts. The subcellular level model is an ODE system and the cellular level model is a hybrid agent-based model of fibroblast migration, proliferationg and collagen production. Our model clearly shows how varying mechanics of the subcellular level system results in varying tissue level pattern (collagen orientation and cell population distribution). The model can be further extended to incorporate subcellular events relating to angiogenesis and wound contraction.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

December 2011

Included in

Life Sciences Commons

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