Roles of cutaneous cell‐cell communication in wound healing outcome: An emphasis on keratinocyte‐fibroblast crosstalk

Abstract

Tissue repair is a very complex event and involves a continuously orchestrated sequence of signals and responses from platelets, fibroblasts, epithelial, endothelial and immune cells. The details of interaction between these signals, which are mainly growth factors and cytokines, have been widely discussed. However, it is still not clear how activated cells at wound sites lessen their activities after epithelialization is completed. Termination of the wound healing process requires a fine balance between extracellular matrix (ECM) deposition and degradation. Maintaining this balance requires highly accurate epithelial‐mesenchymal communication and correct information exchange between keratinocytes and fibroblasts. As it has been reported in the literature, a disruption in epithelialization during the process of wound healing increases the frequency of developing chronic wounds or fibrotic conditions, as seen in a variety of clinical cases. Conversely, the potential stop signal for wound healing should have a regulatory role on both ECM synthesis and degradation to reach a successful wound healing outcome. This review briefly describes the potential roles of growth factors and cytokines in controlling the early phase of wound healing and predominantly explores the role of releasable factors from epithelial‐mesenchymal interaction in controlling during and the late stage of the healing process. Emphasis will be given on the crosstalk between keratinocytes and fibroblasts in ECM modulation and the healing outcome following a brief discussion of the wound healing initiation mechanism. In particular, we will review the termination of acute dermal wound healing, which frequently leads to the development of hypertrophic scarring.

Production and Anti-Inflammatory Performance of PVA Hydrogels Loaded with Curcumin Encapsulated in Octenyl Succinic Anhydride Modified Schizophyllan as Wound Dressings

“…Wound healing is a complex physiological process that requires the synergy of multiple cells during healing [ 52 ]. Keratinocytes and fibroblast cells all play important roles in wound-repair processes [ 53 , 54 ]. In the cell culture media, the hydrogel eventually degrades, releasing elements such as boron.…”

Engineering diabetic human skin equivalent for in vitro and in vivo applications

“…The most appropriate treatment for DFU must be able to promote the proliferation of the patient skin cells, increase the extracellular matrix production to fill up the wounded area, and regulate tissue angiogenesis. The two major cells involved in wound healing are fibroblasts and keratinocytes (Amiri et al, 2022). For diabetic patients, the proliferative capacity of these cells is highly reduced due to the wound site's persistent inflammation (Lerman et al, 2003;Rizwan et al, 2020).…”

Matricellular proteins in cutaneous wound healing

“…The human cutaneous wound healing process goes through four stages: hemostasis, inflammation, proliferation and remodeling ( Amiri et al, 2022 ). First, blood clotting occurs, during the second phase immune cells are recruited to degrade necrotic tissue, phagocyte pathogens, and secrete growth factors, chemokines, and cytokines ( Reinke and Sorg, 2012 ).…”

“…Finally, during the remodeling phase the components of the initial extracellular matrix (e.g., collagen III) are replaced with those of the scar tissue (e.g., collagen I), the wound is contracted, and wound metabolic activity stops ( Reinke and Sorg, 2012 ). The probability of chronic wounds or fibrotic conditions in the skin increases when the re-epithelialization is interrupted or the fine balance between extracellular matrix deposition and degradation is disrupted ( Rousselle et al, 2019 ; Amiri et al, 2022 ). Diverse and highly plastic macrophage populations are critically involved throughout the wound healing process by providing signal molecules for promoting and resolving inflammation, supporting cell proliferation and finally orchestrating tissue restoration (Kim and Nair, 2019; DiPietro et al, 2021 ).…”