Table 2.
Key cells and growth factors involved in tendon healing.
| Key Players in Tendon Healing | |||
|---|---|---|---|
| Cell Type | Primary Phase Present | Primary Function | Reference |
| Erythrocytes | Early inflammatory | Can be present from broken vessels | Connizzo et al. [18] |
| Platelets | Early inflammatory | Clot blood vessels broke in injury, secrete PDGF | Chen et al. [22] |
| Neutrophils | First 24 h | Phagocytose necrotic tissue | Marsolais et al. [20] |
| Macrophages | Inflammatory phase, typically after neutrophils | Phagocytosis; release of growth factors to stimulate fibroblasts, increase ECM synthesis, and decrease ECM degradation | Marsolais et al. [20] |
| Fibroblasts | Inflammatory | Migrate into site of injury | Lomas et al. [19]; Parker et al. [16] |
| Proliferative | Deposit collagen III | ||
| Remodeling | Deposit collagen I | ||
| Tenocytes | Present in tendon for all phases | Contribute to intrinsic tendon healing and collagen formation | Nichols et al. [21] |
| Tendon Stem and Progenitor Cells | Present in sheath for all phases | Differentiate to form mature tenocytes for tissue regeneration | Harvey et al. [3] |
| Growth Factor or Enzyme | Primary Phase Present | Primary Function | Reference |
| PDGF | Inflammatory and remodeling | Induces synthesis of IGF-I and IGF receptors; stimulate collagen, protein, and DNA production; stimulate macrophage migration | Chen et al. [22] |
| IGF-I | Inflammatory and proliferative | Stimulate ECM formation; stimulates migration and proliferation of fibroblasts and tendon stem cells | Miescher et al. [23] |
| VEGF | Proliferative and remodeling | Promotes angiogenesis | Lin et al. [24] |
| TGF-β | All phases | Many functions including collagen production, cell viability, promoting Scx expression | Li et al. [25] |
| bFGF | All phases | Angiogenesis, cellular migration and proliferation; Promotes expression of other growth factors | Lu et al. [26] |
| MMPs | All phases | Degradation and turnover of collagen, glycoproteins, proteoglycans | Andarawis-Puri et al. [7] |
Note that many cells and growth factors are present for multiple phases of healing, but the predominant phase(s) have been listed in this table. Abbreviations. ECM: extracellular matrix, PDGF: platelet-derived growth factor, IGF-I: insulin-like growth factor-I, VEGF: vascular endothelial growth factor, TGF-β: transforming growth factor-beta, Scx: scleraxis, bFGF: basic fibroblast growth factor, MMPs: matrix metalloproteinases.