Figure 4. Simulation of the normal epidermal wound healing process using the ‘virtually injured’ epidermis.

During the healing process, (A) some basal and superbasal cells (labeled with red colour) initially migrated from the wound margins onto the provisional matrix while proliferation/division of these cells was not observed. (B) as the epidermal cells on the wound surface migrated away, there was a burst of keratinocyte proliferation at the wound margins, thus two distinguishable NHK populations (migrative cells (red) and proliferative cells) appeared, (C) due to the cell-ECM interactions, the provisional matrix was remodelled into secondary matrix, (D) when totally covered the denuded area, basal keratinocytes started to stratify and differentiate into TA cells, the secondary matrix was gradually remodelled into basement membrane due to the cell-ECM interactions, (E) TA cells further stratified and differentiated into committed cells and then (F) corneocytes, and finally the virtual epidermal wound was totally re-epithelized. In the integrated model different colours were used to represent keratinocyte stem cells (blue), TA cells (light green), committed cells (dark green), corneocytes (brown), provisional matrix (dark red), secondary matrix (Green), BM tile agent (light purple). Cell agent diameter = 10 µm.