Modelling the interaction of keratinocytes and fibroblasts during normal and abnormal wound healing processes

Abstract

The crosstalk between fibroblasts and keratinocytes is a vital component of the wound healing process, and involves the activity of a number of growth factors and cytokines. In this work, we develop a mathematical model of this crosstalk in order to elucidate the effects of these interactions on the regeneration of collagen in a wound that heals by second intention. We consider the role of four components that strongly affect this process: transforming growth factor-b, platelet-derived growth factor, interleukin-1 and keratinocyte growth factor. The impact of this network of interactions on the degradation of an initial fibrin clot, as well as its subsequent replacement by a matrix that is mainly composed of collagen, is described through an eight-component system of nonlinear partial differential equations. Numerical results, obtained in a twodimensional domain, highlight key aspects of this multifarious process, such as re-epithelialization. The model is shown to reproduce many of the important features of normal wound healing. In addition, we use the model to simulate the treatment of two pathological cases: chronic hypoxia, which can lead to chronic wounds; and prolonged inflammation, which has been shown to lead to hypertrophic scarring. We find that our model predictions are qualitatively in agreement with previously reported observations and provide an alternative pathway for gaining insight into this complex biological process.

Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

“…Surprisingly, the inhibition of curcumin-induced apoptosis in HaCaT cells depends mainly on the induction of ferritin, and less on induction of HO-1. Keratinocytes communicate with both fibroblasts [2][3][4] and immune cells [49] through chemokines and cytokines in wound healing. Impairment of these interactions can affect all phases of cutaneous wound healing.…”

“…The interactions between epidermal keratinocytes and dermal fibroblasts are essential for optimal tissue regeneration and remodeling [2][3][4], and disruptions may lead to pathological wound healing [5][6][7].…”

Angiogenic Peptide Nanofibers Improve Wound Healing in STZ-Induced Diabetic Rats

“…32 Interaction of keratinocytes with fibroblasts is crucial for proper wound healing as these interactions induce the secretion of growth factors and cytokines. 33 The results presented here show that heparin mimetic hydrogel treatment recruits keratinocytes to leading edge and allows their persistent…”

Phenotypic and functional modulation of 20–30 year old dermal fibroblasts by mid- and late-gestational keratinocytes in vitro

“…Therefore, one of the hallmarks of skin wound healing is the proliferation and migration of fibroblasts [5]. Epidermal KCs secrete soluble factors to induce dermal fibroblast proliferation and migration that enhances wound repair through regulation of the production or activity of TGF-b, precollagen, collagen, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) [6,7]. However, the effect of prenatal KCs on postnatal fibroblast wound healing behavior remains unclear.…”