Healing can occur by regeneration or by repair. In regeneration, there is complete restoration of the tissue to normal, while in repair, there is incomplete restoration, and scarring and fibrosis occur.
i) Regeneration: It occurs by the proliferation of parenchymal cells. It depends on the mitotic ability of the injured cell. Cells are classified into three groups depending on their capacity to divide - labile, stable and permanent. Labile cells keep on dividing throughout life. Stable cells have limited division potential and are in resting or G0 phase of the cell cycle, but can still be stimulated to enter the cell cycle when needed. Permanent cells are non-dividing cells and have no potential to divide. As a result, once a permanent cell is injured, it heals by fibrosis.
Type of cell | Examples |
Labile | Epithelial cells of the epidermis, GIT, respiratory, urinary and reproductive tracts; bone marrow, spleen, lymph nodes. |
Stable | Parenchymal cells of the liver, pancreas, kidneys, adrenals, thyroid, smooth muscle, mesenchymal cells, fibroblasts, endothelium, bone, cartilage |
Permanent | Neurons, skeletal muscle, cardiac muscle. |
ii) Repair: Repair is by angiogenesis, followed by fibrogenesis. Granulation tissue is formed in the first phase of the repair. Blood clot forms at the site of injury. Inflammatory processes infuse the injured tissue with cells like neutrophils, platelets and macrophages. Endothelial cells proliferate from the margins of the wound initiating neovascularization and angiogenesis. VEGF or vascular endothelial growth factor, PDGF or platelet derived growth factor, TGF (transforming growth factor) beta, basic fibroblast growth factor or FGF and integrins influence angiogenesis. Newly formed blood vessels are leaky and are present in an amorphous matrix. The wound matrix is composed of collagen, glycoproteins like tissue fibronectin, thrombospondin (from platelets), tenascin, proteoglycans and elastic fibres. The matrix provides structural support, directs cell migration and attachment. Collagen provides tensile strength to the wound while elastic fibres are responsible for wound recoil.
Fibroblasts proliferate and lay down collagen. Some fibroblasts develop into myofibroblasts and have contractile ability. As the wound matures, more collagen is formed while angiogenesis gradually stops. In healing by second intention, with the help of myofibroblasts, the wound starts to contract. Actin filaments in myofibroblasts help in contractility. The wound reaches about 80% of original strength in 3 months. Wound strength is increased by remodelling. Remodelling, or wound maturation, is done by metalloproteinases that convert weaker type III collagen to stronger type I collagen. It starts around the second week and may last up to a year depending on the wound. Presence of infection, poor nutrition (zinc, vitamin C, protein deficiency), diabetes, glucocorticoid use, neutrophil defects, foreign bodies and poor blood supply are some factors that interfere with wound healing. Glucocorticoids interfere with collagen formation and reduce the tensile strength of the wound.
iii) Wound healing: Depending on the type of wound, healing is either by first intention (primary union) or by second intention (secondary union).
Primary union is seen in clean and uninfected wounds, surgical incisions, wounds without much loss of tissue and where the wound edges can be easily approximated with sutures. The following steps are seen in healing by first intention:
Day 1: A blood clot is formed at the site of the wound and bridges the gap between the wound edges. It protects against infection. Neutrophils infiltrate the wound.
Day 2: Basal cells start to proliferate from the wound margins and migrate to close the wound. By 48 hours, the wound is covered by a layer of epithelium. Macrophages reach the wound site.
Day 3: Fibroblasts migrate into the wound by day 3 and start to form collagen. Granulation tissue formation starts.
Days 4-6: Profound granulation tissue, collagen bridges the wound gap.
4 weeks: Scar tissue is formed, remodeling of wound
Secondary union is seen in wounds with a large defect, infected wounds, wounds that are left open without suturing and in the presence of extensive tissue loss. The following steps are seen in healing by second intention:
iv) Healing in specialized tissues: Tissue specific characters are seen in wound healing.
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