From the Guidelines
Fibroblasts are the most essential cells for wound healing. These specialized cells play a central role in the proliferative phase of wound repair by producing collagen and other extracellular matrix proteins that form the structural framework for new tissue 1. When tissue injury occurs, fibroblasts migrate to the wound site, proliferate, and begin synthesizing the components needed to rebuild damaged tissue. They are particularly critical during the second phase of wound healing, transforming into myofibroblasts that contract the wound and bring its edges closer together.
Key Points
- Fibroblasts produce collagen and other extracellular matrix proteins that form the structural framework for new tissue 1.
- They migrate to the wound site, proliferate, and begin synthesizing the components needed to rebuild damaged tissue.
- Fibroblasts are critical during the second phase of wound healing, transforming into myofibroblasts that contract the wound and bring its edges closer together. Without adequate fibroblast activity, wounds cannot properly close or gain tensile strength, leading to delayed healing or chronic wounds. While other cells like macrophages, neutrophils, and keratinocytes are also important in the wound healing process, fibroblasts are indispensable for creating the structural support that allows for complete tissue repair and restoration of function, as supported by recent studies on growth factor-mediated regenerative approaches 1.
Wound Healing Phases
The wound healing process involves four different and partially overlapping phases:
- Hemostasis
- Inflammatory
- Granulation
- Maturation Each phase is crucial for the proper healing of wounds, and fibroblasts play a key role in the granulation phase, where they stimulate the proliferation of new tissue 1.
Growth Factors
Growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF), also play a significant role in wound healing by promoting cell chemotaxis, proliferation, and differentiation 1. However, fibroblasts remain the most essential cells for wound healing, as they are responsible for producing the structural framework for new tissue.
From the Research
Macrophages in Wound Healing
- Macrophages are critically involved in wound healing, from dampening inflammation to clearing cell debris and coordinating tissue repair 2, 3, 4, 5.
- The complexity of macrophage function is increasingly recognized, with adverse outcomes when macrophages are inappropriately activated, such as in fibrosis or chronic non-healing wounds 2.
- Macrophages orchestrate the process of wound healing through the transitioning from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes) 3, 4.
Role of Macrophages in Different Phases of Wound Healing
- Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling 4.
- Non-healing chronic wounds indefinitely remain in inflammation, and local macrophages retain pro-inflammatory characteristics 4.
- Macrophage metabolism also plays a crucial role in wound healing, with unique metabolic requirements of inflammatory and anti-inflammatory macrophages 6.
Importance of Macrophages in Wound Healing
- Macrophages are pivotal orchestrators of inflammation, fibrosis, and wound repair 3.
- Understanding and harnessing the activity and capability of macrophages may help to advance new approaches for improving healing of the skin 3.
- Macrophage dysfunction is a component of the pathogenesis of nonhealing and poorly healing wounds, making them an attractive therapeutic target 5.