Wound Healing
Dr. Raid Jastania
Growth Factors in Repair
• EGF: Epidermal Growth Factor enhances the
proliferation of fibroblasts and endothelial cells.
• PDGF: Platelet-derived Growth Factor is
produced by platelets, macrophages endothelial
cells, and smooth muscle cells. It enhances the
proliferation of fibroblasts and smooth muscle
cells.
• FGF: Fibroblast Growth Factor enhances the
proliferation and recruitment of macrophages and
fibroblasts.
Growth Factors in Repair
• TGF-beta: Transforming Growth Factor-beta is
produced by platelets, endothelial cells, T-cells,
and macrophages.
o Action: In low concentration, it induces PDGF and
proliferation of fibroblasts and smooth muscle. In high
concentration, it inhibit growth and enhances ECM and
collagen synthesis (Fibrosis)
• VEGF: Vascular Endothelial Growth Factor
enhances angiogenesis
• Cytokines: IL-1, TNF induce fibroblast
proliferation
Wound Healing
• Components:
– Cell injury
– Inflammation
– Parenchymal regeneration
– Fibrosis (angiogenesis, fibrosis)
– ECM synthesis / Remodeling of scar
– Modified or loss of tissue function
Healing by First Intention
• Cell injury: focal disruption of the basement
membrane and death of few epithelial cells and
connective tissue.
• Inflammation: Within 24 hours, inflammation
starts as acute inflammation with infiltration of
neutrophils, and exudates. Then after 3 days, the
inflammation is predominated by macrophages.
• Parenchemal regeneration: Within 24 hours,
mitosis and proliferation appear in the basal cells
of the epidermis. This is followed by epithelial
migration and proliferation.
Healing by First Intention
• Fibrosis: The defect is filled with fibrin
(clot) which is gradually removed by the
action of macrophages. In the same time
angiogenesis process starts, accompanied by
early fibrosis (loose connective tissue). The
angiogenesis is peaked in the 5th day, and at
this point we see granulation tissue.
Healing by First Intention
• ECM synthesis:
– ECM forms basement membrane
– Collagen deposition
– By 2 weeks there is resolution of the exudates, no or
minimal inflammatory cells, well-formed capillaries
(vessels) with increased amount of collagen.
– By one month, the defect is replaced by scar tissue
(cellular connective tissue with no inflammation).
Remodeling continues with more deposition of collagen
and decrease in the number of fibroblasts. After few
month, the scar is hypocellular (less fibroblasts) with
firm ECM and much collagen fibers.
Healing by Second Intention
• Extensive tissue loss, with large defect to be
repaired. This occurs in tissue infarctions, abscess
cavity repair.
• There is more fibrin deposition with organization
(rather than resolution)
• There is more severe inflammation
• There is extensive granulation tissue
• Wound contraction occurs by the action of
myofibroblasts.
Wound Strength
• By 1 week, the wound strength is about
10% of the strength of normal skin.
• By 3 months, the wound strength is 70-80%
of the strength of normal skin.
Factors Affecting Repair
Process
Can be intrinsic or extrinsic to the tissue.
• Intrinsic factors include:
– Type of tissue
– Volume of tissue injury
– Location of injury
Factors Affecting Repair
Process
Can be intrinsic or extrinsic to the tissue.
• Extrinsic factors include:
– Infection at site of wound
– Poor perfusion
– Mechanical factors (wound Dehiscence)
– Foreign body
– Nutrition
– Steroid and anti-inflammatory drugs
Chronic Inflammatory
Diseases
• liver fibrosis/cirrhosis
• Crohns disease
• Ulcerative colitis
• Pulmonary fibrosis
• Rheumatoid arthritis