Push or Pull? Cell Proliferation and Migration During Wound Healing

Abstract

Wound healing of the skin is a complex process that is still not well-understood. Wound management is expensive for both individuals and the health system overall, and can reduce quality of life for patients. Given these significant socio-economic impacts, wound healing has long been a focus of scientific research. Recent in vivo mouse studies have identified two key regions in wounded skin tissue: A non-proliferative leading edge that actively migrates into wounded space, and a proliferative hub in which cells have enhanced mitotic properties. This work uses mathematical and computational modelling to investigate the effect of changing the mechanical characteristics of cells in these two key regions. In this paper we explore what characteristics are sufficient for wound healing, particularly focusing on cell proliferation, since wounds are not able to repair successfully without sufficient levels of cell division. By considering contact inhibited proliferation, where small cells are unable to divide, we find that a quiescent region develops if the proliferative hub is able to grow over time, essentially limiting the number of cells that are able to divide. In contrast, if the size of the proliferative hub is kept below some threshold, then contact inhibition has a less significant role in wound repair. This work builds upon existing cell-based computational studies of wound healing and could be modified to investigate different stages of wound healing, impaired healing and wound treatments.