Definition of Granulation Tissue
Granulation tissue is new connective tissue that forms during wound healing, characterized by proliferation of fibroblasts, myofibroblasts, small blood vessels, and inflammatory cells within a loose collagen matrix that fills tissue defects and serves as the foundation for subsequent scar formation or epithelialization. 1
Histologic Composition
Granulation tissue consists of several key cellular and structural components:
- Fibroblasts and myofibroblasts embedded in loose collagen constitute the primary cellular elements, with myofibroblasts expressing alpha-smooth muscle actin and mediating wound contraction 1, 2
- Small vessel proliferation (angiogenesis) provides the characteristic pink, granular appearance and delivers oxygen and nutrients to the healing tissue 1, 2
- Inflammatory cells including macrophages and lymphocytes populate the tissue and coordinate the healing response 1, 3
- Loose extracellular matrix with minimal collagen deposition distinguishes granulation tissue from mature scar tissue 1
Temporal Characteristics and Distribution
The tissue demonstrates specific patterns during wound healing:
- Uniform, recent temporal appearance characterizes normal granulation tissue, indicating synchronized healing processes 1
- Patchy distribution often occurs, particularly in conditions like bronchiolitis obliterans organizing pneumonia where granulation tissue extends through pores of Kohn creating a "butterfly" pattern 1
- Foamy macrophages commonly appear in alveolar spaces when granulation tissue causes airway occlusion 1
Functional Role in Wound Healing
Granulation tissue serves critical functions during tissue repair:
- Fills tissue defects created by injury, providing a scaffold for new tissue growth and eventual epithelialization 4, 3
- Initiates regenerative processes including M2 macrophage polarization, fibroblast proliferation, myofibroblast differentiation with wound contraction, neovascularization, and matrix deposition 3
- Separates wound edges when present in excess (hypergranulation), which requires intervention to allow epithelial migration 5
Evolution to Scar Tissue
The transition from granulation tissue to mature scar involves a critical cellular reduction:
- Apoptosis mediates cellularity decrease as granulation tissue matures into scar, with myofibroblasts and vascular cells undergoing programmed cell death as the wound closes 2, 6
- Striking decrease in cellularity occurs during scar formation, with typical myofibroblasts disappearing through apoptotic mechanisms 2, 6
- Increased apoptosis correlates with wound closure, supporting the mechanism by which granulation tissue evolves into less cellular scar tissue 2
Pathologic Variations
Excessive Granulation (Hypergranulation)
- Excess granulation tissue beyond the tissue deficit characterizes hypergranulation, appearing as tissue that protrudes above the wound surface 7
- Impairs epithelialization by creating a physical barrier that prevents epithelial cell migration across the wound surface 5, 7
- Multiple contributing factors include infection, excessive moisture, foreign body reaction, and mechanical irritation 5
Impaired Granulation Formation
- Delayed wound healing or excessive scarring results from defective granulation tissue formation, representing conditions with high morbidity and mortality 3
- Stalled wounds with granulation tissue that has plateaued require intervention to restart the healing cascade 4
Clinical Implications
Understanding granulation tissue characteristics guides therapeutic decisions:
- Normal granulation tissue appears pink, granular, and bleeds easily due to rich vascular supply 1, 3
- Healthy granulation tissue formation is encouraged in wounds where primary closure is not possible, creating a suitable surface for skin grafting 5
- Negative pressure wound therapy stimulates granulation tissue formation through mechanical means and increased tissue perfusion 1, 8