Regeneration and repair: wound and bone healing. Stages of the reparative process.
See above for definitions of regeneration and repair.
Bone healing
The phases of bone healing are:
- Reactive phase
- Fracture and inflammatory phase
- Granulation tissue formation
- Reparative phase
- Cartilage callus formation - this bridges the gap in broken bone
- Woven bone deposition - bone replaces the cartilage cap (endochondral ossification)
- Remodelling phase
- Remodeling bone to original contour - woven bone replaced with lamellar (compact) bone
Remember: a fracture first fills with a haematoma, which is organised into granulation tissue within days; by about a week a soft callus of fibrous tissue and cartilage bridges the ends; this is replaced by woven bone (bony callus) over the next weeks, and over months the callus is remodelled into lamellar bone along the lines of stress.
Stages of wound healing process
- Hemostasis
- Following initial injury there is an outflow of blood and lymph. This activates clotting mechanisms with instant vasoconstriction followed by vasodilation. This vasodilation allows for the movement of lymphocytes and other cells into the interstitial.
- Vasoconstriction is mediated by thromboxane A2 from platelets and endothelin released from the endothelium, with vasodilation being predominantly mediated by histamine released by mast cells.
- Inflammatory phase
- With vasodilation there is an influx of fluid into the interstitial. Within an hour of wounding neutrophils are in the wound region, helping to kill bacteria. This is along with T-helper cells releasing cytokines to activate cellular immunity.
- After a few days, neutrophils die off, and macrophages begin to dominate. These help to mediate the early stages of proliferation.
- Proliferative (Granulation) phase
- 2-3 days after the wound occurs, fibroblasts enter the wound and begin the proliferative phase. This begins with two distinct processes, angiogenesis, the vasculation of the region, mediated by vascular endothelial growth factor, and fibroplasia and granulation formation, mediated by fibroblasts, stimulated by TGF-beta and Platelet Derived Growth Factor.
- Once the granulation tissue has been laid down, reepithelialization can occur. Basal keratinocytes are the main cells responsible for the laying down of such cells.
- As reepithelialization occurs the wound undergoes contraction, this is a key figure in wound healing and is marked by the laying down of actin from myofibroblasts which help to pull the edges of the wound together.
- Remodelling (maturation) phase