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