Wound Healing

Two Key processes in tissue repair

• Regeneration

• Scar formation

What cells play a central role in repair?

Macrophages

Wound with clean, close edges such as a surgical incision or paper cut. Minimal scarring

Primary Intention

Wound that is larger and more open such as an extraction site, burns, graft site that leads to more granulation and scarring

Secondary Intention

Three cells / tissue that proliferate in regeneration

• Injured tissue

• Vascular endothelial cells

• Fibroblasts

Repair Sequence

• Immediately: Clot forms

• Day 1: Neutrophils migrate, phagocytose foreign substance

• Day 2: Macrophages enter, granulation tissue forms, protected by fibrin clot

• Day 3-6: Lymphocytes and Plasma cells enter

• Day 7: Clot digested

• Day 14: Fibroblast mature, collagen remodeled to form scar tissue

When do Scars form?

When regeneration is not possible

• Permanent tissue

• Extensive ECM damage

Condition from excessive scar tissue, often seen in chronic inflammation

Fibrosis

What signals the formation of new blood vessels to supply healing nutrients?

VEGF

Migration of fibroblasts is mediated by what?

Fibroblast Growth factor (FGF) made by macrophages

Tissue formed by new blood vessels and fibroblasts, appears red/pink 3-5days post injury

Granulation Tissue

What does this image show?

Granulation Tissue

Fibroblasts depositing collagen is mediated by what?

TGF-beta

Granuloma Vs Granulation Tissue

• Granuloma: part of inflamm. process, macrophages, maybe surrounding lymphocytes

• Granulation Tissue: created during tissue repair, new BV and fibroblasts

Role of TGF-beta in scar formation

Stimulates production and inhibits breakdown of ECM proteins (and anti-inflamm)

Role of Platelelt derived growth factor (PDGF) in scar formation

Migration and proliferation of fibroblasts and Smooth muscle cells

Role of Fibroblast growth factor (FGF) in scar formation

Fibroblast migration

Role of Cytokine IL-13 in scar formation

Stimulates collagen and fibroblast migration

List factors that can prevent healing and repair

• Infection

• Nutrition (Vit. C deficiency)

• Steroid use

• Poor perfusion

• foreign bodies

• type and extent of injury

• Location of injury

Excessive formation of collagen leads to what?

Keloids

What can remodel connective tissue over time?

Matrix Metalloproteinases (MMPs)

Granulation tissue is primarily composed of which of the following?

• Neutrophils and macrophages

• Fibroblasts and new BVs

• epithelial cells and blood clots

• Scar tissue and fibroblasts

• Lymphocytes and collagen

Fibroblasts and new blood vessels