Inflammation-Associated Wound Healing through a Monocytic Lens

The development of macrophages from monocytes during wound healing is a complicated and convoluted process. Classically or alternatively activated macrophages result from a complex network of cytokine signaling between circulating monocytes entering tissue, resident macrophages, and stromal fibroblasts. This network of signaling constitutes a continuous communication between these cell types, influencing factors such as inflammatory duration, healthy or fibrotic tissue repair, and downstream macrophage functionality. “Forward talk” from monocytes to fibroblasts, as well as “back talk” from fibroblasts to monocytes, can greatly influence the behavior of each cell type. This cell-cell communication, though difficult to fully encapsulate in vitro, can be facilitated through implementation of specific cell culture techniques. 3D cell culture systems enable a more representative assessment of myofibroblast phenotypes that would likely be seen during wound repair. Co-culture systems further enable cell-cell interactions in the inflammatory and wound repair cascades to be assessed in coordination with each other. Looking ahead, these cell culture techniques, alongside novel concepts such as organ-on-a-chip models, can provide deeper insight into the myriad molecular mechanisms we claim to understand currently. Our improved understanding of these cellular interactions can lead to improved clinical outcomes for pathologies associated with these complex cell types