Types of healing processes 

a. Healing by regeneration

  Definition: Regeneration (generare=bring to life) is the renewal of a lost tissue in which the lost cells are replaced by identical ones. 

Regeneration involves two processes 

1.  Proliferation of surviving cells to replace lost tissue 

2.  Migration of surviving cells into the vacant space. 

 The capacity of a tissue for regeneration depends on its 

1) proliferative ability,

2)  degree of damage to stromal framework and 

3)  on the type and severity of the damage. 

Tissues formed of labile and stable cells can regenerate provided that stromal framework are intact.

b. Repair (Healing by connective tissue)  

 Definition:- Repair is the orderly process by which lost tissue is eventually replaced by a scar. 

 A wound in which only the lining epithelium is affected heals exclusively by regeneration. In contrast, wounds that extend through the basement membrane to the connective tissue, for example, the dermis in the skin or the sub-mucosa in the gastrointestinal tract, lead to the formation of granulation tissue and eventual scarring. Tissues containing terminally differentiated (permanent) cells such as neurons and skeletal muscle cells can not heal by regeneration. Rather the lost permanent cells are replaced by formation of granulation tissue. 

In granulation-tissue formation, three phases may be observed.

1. Phase of inflammation

 At this phase, inflammatory exudate containing polymorphs is seen in the area of tissue injury. In addition, there is platelet aggregation and fibrin deposition. 

 2. Phase of demolition

 The dead cells liberate their autolytic enzymes, and other enzymes (proteolytic) come from disintegrating polymorphs. There is an associated macrophage infiltration. These cells ingest particulate matter, either digesting or removing it.

3. Ingrowth of granulation tissue

 This is characterized by proliferation of fibroblasts and an ingrowth of new blood vessels into the area of injury, with a variable number of inflammatory cells. 

Fibroblasts actively synthesize and secrete  extra-cellular matrix components, including fibronectin, proteoglycans, and collagen types I and III. The fibronectin and proteoglycans form the ‘scaffolding’ for rebuilding of the matrix. Fibronectin binds to fibrin and acts as a chemotactic factor for the recruitment of more fibroblasts and macrophages. The synthesis of collagen by fibroblasts begins within 24 hours of the injury although its deposition in the tissue is not apparent until 4 days. By day 5, collagen type III is the predominant matrix protein being produced; but by day 7 to 8, type I is prominent, and it eventually becomes the major collagen of mature scar tissue. This type I collagen is responsible for providing the tensile strength of the matrix in a scar. 

Coincident with fibroblast proliferation there is angiogenesis (neovascularization), a proliferation and formation of new small blood vessels. Vascular proliferation starts 48 to 72 hours after injury and lasts for several days.

With further healing, there is an increase in extracellular constituents, mostly collagen, with a decrease in the number of active fibroblasts and new vessels. Despite an increased collagenase activity in the wound (responsible for removal of built collagen), collagen accumulates at a steady rate, usually reaching a maximum 2 to 3 months after the injury.

The tensile strength of the wound continues to increase many months after the collagen content has reached a maximum.  As the collagen content of the wound increases, many of the newly formed vessels disappear. This vascular involution which takes place in a few weeks, dramatically transforms a richly vascularized tissue in to a pale, avascular scar tissue. 

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.