Mathematical investigation of normal and abnormal wound healing dynamics: local and non-local models.

The movement of cells during (normal and abnormal) wound healing is the result of biomechanical interactions that combine cell responses with growth factors as well as cell-cell and cell-matrix interactions (adhesion and remodelling). It is known that cells can communicate and interact locally and non-locally with other cells inside the tissues through mechanical forces that act locally and at a distance, as well as through long non-conventional cell protrusions. In this study, we consider a non-local partial differential equation model for the interactions between fibroblasts, macrophages and the extracellular matrix (ECM) via a growth factor (TGF-$ \beta $) in the context of wound healing. For the non-local interactions, we consider two types of kernels (i.e., a Gaussian kernel and a cone-shaped kernel), two types of cell-ECM adhesion functions (i.e., adhesion only to higher-density ECM vs. adhesion to higher-/lower-density ECM) and two types of cell proliferation terms (i.e., with and without decay due to overcrowding). We investigate numerically the dynamics of this non-local model, as well as the dynamics of the localised versions of this model (i.e., those obtained when the cell perception radius decreases to 0). The results suggest the following: (ⅰ) local models explain normal wound healing and non-local models could also explain abnormal wound healing (although the results are parameter-dependent); (ⅱ) the models can explain two types of wound healing, i.e., by primary intention, when the wound margins come together from the side, and by secondary intention when the wound heals from the bottom up.

Modelling Keloids Dynamics: A Brief Review and New Mathematical Perspectives.

Keloids are fibroproliferative disorders described by excessive growth of fibrotic tissue, which also invades adjacent areas (beyond the original wound borders). Since these disorders are specific to humans (no other animal species naturally develop keloid-like tissue), experimental in vivo/in vitro research has not led to significant advances in this field. One possible approach could be to combine in vitro human models with calibrated in silico mathematical approaches (i.e., models and simulations) to generate new testable biological hypotheses related to biological mechanisms and improved treatments. Because these combined approaches do not really exist for keloid disorders, in this brief review we start by summarising the biology of these disorders, then present various types of mathematical and computational approaches used for related disorders (i.e., wound healing and solid tumours), followed by a discussion of the very few mathematical and computational models published so far to study various inflammatory and mechanical aspects of keloids. We conclude this review by discussing some open problems and mathematical opportunities offered in the context of keloid disorders by such combined in vitro/in silico approaches, and the need for multi-disciplinary research to enable clinical progress.