Fig. 1.

Healing by secondary intention involves the closure of a large open defect, and in skin wound healing proceeds through stages that effect repair approaching the original tissue via a wave of signaling factors that orchestrate the cells to generate a paucicellular barrier to the external hostile environment. It is critical that early in the process pro-stimulatory signals recruit cells to replace the lost tissue. However, late in the tissue formation and early in the tissue remodeling phase, other signals are needed to shut off this exuberant response. Growth factors and chemokines function during these phases as “stop” signals. CXCL11/IP-9 is made by redifferentiated keratinocytes that have covered their denuded provisional matrix and CXCL10/IP-10 is produced by nascent blood vessels. These chemokines maintain the de-differentiated state of migrating keratinocytes while causing the dermal fibroblasts to ‘differentiate’ to produce mature matrix. (Note, the initial stage of hemostasis is not shown here)