Myofibroblasts and fibroblasts play crucial roles in wound healing and tissue repair. These cells are embedded in an extracellular matrix (ECM) and interact with their microenvironment to regulate tissue remodeling. They secrete ECM components and matrix metalloproteinases, enabling ECM remodeling. Myofibroblasts are characterized by their expression of α-smooth muscle actin (α-SMA) and their ability to contract, contributing to wound contraction and tissue maturation. However, in pathological conditions such as fibrosis or excessive scarring, myofibroblasts may persist, leading to abnormal tissue remodeling and scarring. Myofibroblasts originate from local fibroblasts, mesenchymal stem cells, fibrocytes, and cells undergoing epithelial-mesenchymal transition. Their differentiation is influenced by mechanical signals, growth factors, and the ECM. Mechanical stress can enhance myofibroblast contraction and survival, while reduced stress can induce apoptosis and decrease α-SMA expression. Hypoxia also affects myofibroblast function, with acute hypoxia promoting wound healing but chronic hypoxia potentially exacerbating fibrosis. Myofibroblasts are involved in various fibrotic diseases, including liver, kidney, and lung fibrosis, as well as cancer progression. Their activity is regulated by factors such as TGF-β, which promotes fibrosis through Smad3 signaling. Therapeutic strategies targeting myofibroblasts include inhibiting TGF-β signaling, blocking integrin-mediated activation of TGF-β, and using drugs like pirfenidone and imatinib to reduce fibrosis. Additionally, statins may have anti-fibrotic effects by inhibiting ROCK. Understanding myofibroblast biology is essential for developing therapies to improve wound healing and reduce scarring. Myofibroblasts also interact with the nervous system, with peripheral nerve damage affecting wound healing. Future research aims to better regulate myofibroblast activity to enhance tissue repair and prevent pathological fibrosis.Myofibroblasts and fibroblasts play crucial roles in wound healing and tissue repair. These cells are embedded in an extracellular matrix (ECM) and interact with their microenvironment to regulate tissue remodeling. They secrete ECM components and matrix metalloproteinases, enabling ECM remodeling. Myofibroblasts are characterized by their expression of α-smooth muscle actin (α-SMA) and their ability to contract, contributing to wound contraction and tissue maturation. However, in pathological conditions such as fibrosis or excessive scarring, myofibroblasts may persist, leading to abnormal tissue remodeling and scarring. Myofibroblasts originate from local fibroblasts, mesenchymal stem cells, fibrocytes, and cells undergoing epithelial-mesenchymal transition. Their differentiation is influenced by mechanical signals, growth factors, and the ECM. Mechanical stress can enhance myofibroblast contraction and survival, while reduced stress can induce apoptosis and decrease α-SMA expression. Hypoxia also affects myofibroblast function, with acute hypoxia promoting wound healing but chronic hypoxia potentially exacerbating fibrosis. Myofibroblasts are involved in various fibrotic diseases, including liver, kidney, and lung fibrosis, as well as cancer progression. Their activity is regulated by factors such as TGF-β, which promotes fibrosis through Smad3 signaling. Therapeutic strategies targeting myofibroblasts include inhibiting TGF-β signaling, blocking integrin-mediated activation of TGF-β, and using drugs like pirfenidone and imatinib to reduce fibrosis. Additionally, statins may have anti-fibrotic effects by inhibiting ROCK. Understanding myofibroblast biology is essential for developing therapies to improve wound healing and reduce scarring. Myofibroblasts also interact with the nervous system, with peripheral nerve damage affecting wound healing. Future research aims to better regulate myofibroblast activity to enhance tissue repair and prevent pathological fibrosis.