TABLE 1.
SUMMARY OF COMPONENTS INVOLVED IN AGENT-BASED MODEL
| Substances | Cell Sources | Biological Functions in Wound Healing Used in Agent-Based Model |
|---|---|---|
| TGF-β1 | Platelets | Chemotactic to neutrophils, macrophages, and fibroblasts |
| Macrophages | Inhibit expression of TNF-α in neutrophils, macrophages, and fibroblasts | |
| Fibroblasts | Inhibit expression of MMP-8 in neutrophils | |
| Inhibit expression of IL-1β in macrophages (minimal effect) | ||
| Activate resting fibroblasts | ||
| Mitogenic to fibroblasts (proliferation) | ||
| Stimulate collagen synthesis in fibroblasts | ||
| Stimulate elastin synthesis in fibroblasts | ||
| Stimulate hyaluronan synthesis in fibroblasts | ||
| bFGF | Macrophages | Chemotactic to neutrophils and macrophages |
| Fibroblasts | Mitogenic to fibroblasts (proliferation) | |
| Stimulate fibroblast migration | ||
| Inhibit collagen synthesis in fibroblasts | ||
| Inhibit elastin synthesis in fibroblasts | ||
| Stimulate hyaluronan synthesis in fibroblasts | ||
| TNF-α | Neutrophils | Chemotactic to neutrophils and macrophages |
| Macrophages | Activate neutrophils and macrophages | |
| Fibroblasts | Stimulate expression of MMP-8 in neutrophils | |
| Stimulate expressions of TNF-α, IL-1β, IL-6, and IL-8 in macrophages | ||
| Stimulate expression of TGF-β in macrophages and fibroblasts | ||
| Mitogenic to fibroblasts (proliferation) | ||
| Stimulate expression of IL-6 in fibroblasts | ||
| Inhibit elastin synthesis in fibroblasts | ||
| Stimulate hyaluronan synthesis in fibroblasts | ||
| Induce tissue damage | ||
| IL-1β | Platelets | Chemotactic to neutrophils and macrophages |
| Macrophages | Activate macrophages | |
| Stimulate expressions of TNF-α, IL-1β, IL-6, and IL-8 in macrophages | ||
| Mitogenic to fibroblasts (proliferation) | ||
| Inhibit collagen synthesis in fibroblasts | ||
| Inhibit elastin synthesis in fibroblasts | ||
| Stimulate hyaluronan synthesis in fibroblasts | ||
| IL-6 | Macrophages | Chemotactic to neutrophils |
| Fibroblasts | Stimulate collagen synthesis in fibroblasts | |
| IL-8 | Macrophages | Chemotactic to neutrophils |
| Fibroblasts | Inhibit collagen synthesis in fibroblasts | |
| IL-10 | Macrophages | Inhibit expression of TNF-α in neutrophils, macrophages, and fibroblasts |
| Inhibit expression of IL-1β in macrophages | ||
| Inhibit expressions of IL-6 and IL-8 in macrophages and fibroblasts | ||
| Stimulate expression of TGF-β in macrophages and fibroblasts | ||
| Stimulate expression of IL-10 in macrophages | ||
| Inhibit activated neutrophil survival | ||
| Inhibit activation of neutrophils and macrophages | ||
| MMP-8 |
Platelets Neutrophils |
Degrade collagen to produce collagen fragments |
| Collagen (type 1) | Fibroblasts | Collagen repairs tissue damage |
| Collagen fragments are chemotactic to neutrophils and macrophages | ||
| Elastin | Fibroblasts | Elastin repairs tissue damage |
| Elastin fragments are chemotactic to macrophages | ||
| HA | Fibroblasts | HA repairs tissue damage |
| HA inhibits expression of TNF-α and IL-8 in fibroblasts | ||
| HA inhibits collagen synthesis in fibroblasts | ||
| HA fragments stimulate expressions of TNF-α, IL-1β, and IL-8 in macrophages | ||
| HA fragments are mitogenic to fibroblasts (proliferation) | ||
| HA fragments stimulate collagen synthesis in fibroblasts |
Items in italics represent extension of existing agent-based model.
TGF — transforming growth factor; TNF — tumor necrosis factor; MMP — matrix metalloproteinase; IL — interleukin; bFGF — basic fibroblast growth factor; HA — hyaluronan.