Fibroblasts – the cellular choreographers of wound healing

Abstract

Injuries to our skin trigger a cascade of spatially- and temporally-synchronized healing processes. During such endogenous wound repair, the role of fibroblasts is multifaceted, ranging from the activation and recruitment of innate immune cells through the synthesis and deposition of scar tissue to the conveyor belt-like transport of fascial connective tissue into wounds. A comprehensive understanding of fibroblast diversity and versatility in the healing machinery may help to decipher wound pathologies whilst laying the foundation for novel treatment modalities. In this review, we portray the diversity of fibroblasts and delineate their unique wound healing functions. In addition, we discuss future directions through a clinical-translational lens.

Dual network composite hydrogels with robust antibacterial and antifouling capabilities for efficient wound healing

“…Instead, these dressings adhere to the wound surface by absorbing wound exudate, causing pain upon removal, and potentially damaging newly formed tissue. Most importantly, they are unable to inhibit skin wound scar formation, 11–14 which causes obvious scars to form after wound healing and affects skin aesthetics. In summary, traditional wound dressings cannot meet the various needs of wound healing due to their limitations, and multifunctional wound dressings that inhibit scar formation are becoming a research focus.…”

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing

“…These fibroblasts were proposed to arise mainly from self-proliferation or the differentiation of nearby mesenchymal cells. 20 The contradictory findings regarding the impact of hucMSC-EVs on fibroblast differentiation, 21,22 coupled with the scarce research on the effects of hucMSC-EVs on fibroblast-keratinocyte interactions in the context of wound healing, highlight the necessity for a thorough investigation. Here, we utilized the single-cell RNA sequencing (scRNAseq) platform to conduct a high-resolution analysis of murine skin wounds treated with and without hucMSC-EVs.…”

“…The ECM also facilitates the migration of keratinocytes to achieve re-epithelialization. These fibroblasts were proposed to arise mainly from self-proliferation or the differentiation of nearby mesenchymal cells . The contradictory findings regarding the impact of hucMSC-EVs on fibroblast differentiation, , coupled with the scarce research on the effects of hucMSC-EVs on fibroblast-keratinocyte interactions in the context of wound healing, highlight the necessity for a thorough investigation.…”

In vitro effects of wound‐dressings on key wound healing properties of dermal fibroblasts

“…Fibroblast dysfunctions, in particular those depending on TGF‐β signalling, alter wound healing and can lead to the development of chronic wounds 1,11,12 . On the contrary, prolonged fibroblast activities (excess ECM deposition, proliferation or contraction) induce disorders such as fibrosis and hypertrophic scars 10 . Keratinocytes, responsible for the re‐epithelisation of the wound surface (wound closure), participate in fibroblast regulation and are important for wound healing termination 13,14 …”