Tissue healing/repair

Question 1

What are the phases of tissue repair by scarring?

Answer 1

1) Inflammation -> clearing of the offending agen, removal of debris
M1 macrophages clear necrotic tissue and M2 macrophages produce wound repair and fibrosis TGF-beta.

2) Cell proliferation and deposition of connective tissues - can take up to 10 days
Proliferation of epithelial cells, endothelial cells (angiogenesis, VEGF, TGF-B)
Proliferation of fibroblasts -> granulation tissue (collagen) - epithelial cells grow over the granulation tissue.

3) Remodeling - months to years
- Collagen crosslinking - increase in collagen size to increase the strength of the wound.
Switch form type III to type I collagen.

The scar then needs to shrink, and this is done with matrix metalloproteinases, which degrade tissues. This is produced by fibroblasts, neutrophils and macrophages.

Not a return to normal tissue, i.e. no hair follicles

Question 2

What factors impair healing?

Answer 2

1) Infection
2) Diabetes - decreased blood flow and hyperglycaemia impairs leukocyte function
3) Poor nutrition - vit C deficiency
4) Glucocorticoids inhibit TGF-beta production and reduce fibrosis.
5) Mechanical factors - tension, pressure, torsion
6)Foreign bodies - Chronic inflammation
7) poor perfusion (PVD, obstructed venous drainage = decreased leukocyte migration and decreased oxygenation
8) Location of injury

Question 3

Comment ->

Answer 3

Restoration of normal architecture can only happen if tissue architecture is structurally intact

Question 4

How is scar tissue formed?

Answer 4

Within minutes a hemostatic platelet plug is formed. Inflammatory cells are recruited, including neutrophils and monocytes.
The inflammatory cells eliminate any offending agents.
M2 macrophages produce growth factors that stimulate the proliferation of cells.

In the next 10 days of repair, the cells proliferate, including epithelial, endothelial, fibroblasts. They then migrate to close the wound
- Epithelial cells migrate to cover the wound
- Endothelial cells form new blood vessels
- Fibroblasts proliferate and migrate into the site of injury to lay down collagen fibrers.
- Myofibroblasts have actin and contract to close the wound

These cells form granulation tissue.

Reorganization of the connective tissue then occurs to form a stable scar. This starts 2-3 weeks after injury and can take months to years.
Matrix metalloproteinases degrade and shrink the scar (these are inhibited by tissue inhibitors of MMP (TIMP)

TGF-beta is the main cytokine in scar formation