Cannot divide; loss is irreversible and healed by scar
Neurones, cardiac muscle, skeletal muscle (limited, via satellite cells)
Regeneration also needs an intact connective tissue framework — the liver regenerates after partial resection but scars in cirrhosis, because the reticulin framework is destroyed
Granulation Tissue
Granulation tissue is the hallmark of healing: newly formed capillaries, proliferating fibroblasts and inflammatory cells in a loose oedematous matrix.
Soft, pink and granular to the naked eye, bleeding easily
Named from its appearance, not from granulomas — a persistent source of confusion
Progressively becomes less vascular and more collagenous, ending as a pale avascular scar
Healing BY First Intention (primary Union)
Time
Events
0–24 hours
Clot fills the narrow incision; neutrophils appear at the margins
24–48 hours
Epithelial cells migrate from both edges and fuse beneath the surface scab
Day 3
Neutrophils are replaced by macrophages; granulation tissue invades
Day 5
Granulation tissue is maximal; neovascularisation is at its peak; collagen begins to bridge the incision
Week 2
Continued collagen accumulation and fibroblast proliferation; the inflammatory infiltrate, oedema and vascularity all diminish
Month 1
A scar of cellular connective tissue covered by intact epidermis, free of inflammatory cells
Tensile strength is only about 10% at one week; it rises rapidly over 4 weeks and reaches 70–80% of normal by 3 months, which it never exceeds
This is why sutures are removed at about a week but the patient is warned against strain for months
Healing BY Second Intention (secondary Union)
Feature
First intention
Second intention
Wound
Clean, incised, edges apposed, minimal tissue loss
Large, with tissue loss; edges cannot be apposed
Clot and necrotic debris
Minimal
Abundant
Inflammation
Slight
Intense
Granulation tissue
Small amount
Large amount
Wound contraction
Negligible
Marked — may reduce the defect by 70–80%, by myofibroblasts
Scar
Fine, linear
Large, sometimes disfiguring
Time
Days to weeks
Weeks to months
Infection
Uncommon
Common
CLINICAL PEARL
Wound contraction is the work of myofibroblasts, fibroblasts that have acquired the contractile apparatus of smooth muscle. It is enormously useful in closing a large defect, but the same mechanism produces the contracture that deforms a healed burn and limits joint movement — the same process, beneficial or crippling depending on site.
Factors Influencing Healing
Local factors
Systemic factors
Infection — the single most important cause of delay
Nutrition — protein and vitamin C deficiency; zinc
Foreign body
Diabetes mellitus — microangiopathy, neuropathy and impaired leucocyte function
Poor blood supply and venous stasis
Corticosteroids — inhibit collagen synthesis and the inflammatory response
Movement of the wound
Age — healing is slower in the aged
Size, type and site of the wound
Malignancy, uraemia, jaundice
Irradiation and previous surgery
Anaemia and hypoxia; chemotherapy
Growth Factors in Healing
Factor
Source
Chief action
PDGF
Platelets, macrophages
Chemotaxis and proliferation of fibroblasts and smooth muscle
VEGF
Macrophages, mesenchymal cells
Angiogenesis; also increases vascular permeability
FGF-2
Macrophages, endothelium
Angiogenesis and fibroblast proliferation
TGF-beta
Platelets, macrophages, lymphocytes
The chief fibrogenic factor — stimulates collagen synthesis and inhibits its degradation; also anti-inflammatory
EGF and TGF-alpha
Platelets, macrophages, saliva
Proliferation of epithelial cells — re-epithelialisation
TGF-beta is the key to fibrosis everywhere — excessive activity underlies keloid, hepatic cirrhosis and pulmonary fibrosis alike, and it is the target of most anti-fibrotic research
Matrix metalloproteinases remodel collagen and require zinc; they are balanced by tissue inhibitors, and the balance decides whether a scar matures or thickens
Complications and Applied Aspects
Deficient scar formation — wound dehiscence and incisional hernia; commonest after abdominal surgery with raised intra-abdominal pressure
Excessive formation — hypertrophic scar stays within the wound boundary and often regresses; keloid grows beyond it, does not regress, recurs after excision, and is far commoner in dark skin — a frequent problem in Indian practice
Exuberant granulation ("proud flesh") protrudes above the surface and prevents epithelialisation; treated by cautery or excision
Contracture after burns, especially across a flexor surface, requires splinting, physiotherapy and often surgical release
Vitamin C is required for the hydroxylation of proline and lysine; without it collagen is unstable, old scars break down, and this is the mechanism of scurvy
Malignant change in a chronic scar or sinus — the Marjolin ulcer, a squamous carcinoma arising in a burn scar or chronic osteomyelitis sinus
