Table 3.
Kinetics of wound healing of the muscle: main phases and players
| Destruction | Repair | Remodeling | |
|---|---|---|---|
| Days following injury | |||
| When | 1 to 5 | 3 to 7 | 8 to weeks |
| Where | hematoma (between fiber stumps) | necrotic segment | newborn fibers regenerated segment |
| What | phagocytosis of necrotized tissue inflammation Satellite cell activation | myofiber formation (fusion of muscle precursor cells) | myofiber growth |
| gap refilling (myotube fusion with each other and surviving fibers) | myofiber function (fiber type specif.) scar reorganization | ||
| Who | muscle fibers (1) (2) | muscle fibers (4) (5) | fiber cytoskeleton (7) |
| muscle fibers (3) | nerve sprouts (8) | ||
| connective tissue (4) | intervening scar (9) | ||
| macrophages (4) | |||
| neutrophils (5) | |||
| How | HGF (1) | IGF-1 and−2 (4) | myofibril remodeling (7) |
| FGF-1-2-4 and-6 (2) | IL-4 (5) | nerve activity (frequency)(8) | |
| MSTN/GDF8 (3) (4) | scar retraction (9) | ||
| LIF (3) (4) | |||
| TNF (5) | |||
Following injury, regeneration of the muscle can be schematically divided in three main phases. Complete muscle regeneration in humans may take several weeks. In addition to the timeline (When), each row indicates the tissue involved (Where), the main output (What), the cell type involved most (Who) and some of the main molecular mediators (How) responsible for the various phases of wound healing. Matching superscripts highlight the cells that produce the corresponding growth factors or the cellular structures responsible for a given function. Fibroblast growth factor (FGF); hepatocyte growth factor (HGF); insulin-like growth factor (IGF); interleukin-4 (IL-4); leukemia inhibitory factor (LIF); myostatin (MSTN), also known as growth differentiation factor 8 (GDF-8); tumor necrosis factor (TNF).