Tissue Repair

Regeneration

Replacement of injured cells by cells of same type

Labile Cells

Continuously dividing cells

Follow cell cycle from one mitosis to the next

Proliferate to replace cells

Regen. derived mostly from stem cells with unlimited regen capacity

Stratified sq. cells of skin, columnar epithelium of GI tract

Stable Cells

Quiescent cells

Normally low level or replication

Rapid division in response to stimuli

Capable of rebuilding tissue of origin

Considered to be G0 but can be stimulated into G1

E.g.

Mesenchymal cells

Vascular endothelial cells

Parenchymal cells of glandular organs

Restitution of normal structure

Needs intact basement Membrane

Underlying supporting stroma of parenchymal cells

Needed for organized regeneration

Cells proliferate haphazrdly if BM disrupted

Fibrosis

Replacement of injured cells by connective tissue

1) Angiogenesis

a) Proteolytic Degradation

BM of parent vessel

b) Migration and proliferation of Endothelial Cells

To angiogenic stimulus

c) Maturation of Cells

Inhibition and remodeling into capillary tubes

d) Recruitment of periendothelial cells

Pericytes

Smooth muscle cells

2) Migration + Proliferation of Fibroblasts

Proliferation triggered by GFs and Cytokines

Formation of granulation tissue framework

3) Deposition of ECM

major portion of connective tissue formed by fibrillar collagens

Fibroblast proliferation decreases over time while ECM deposition increases

4) Remodelling of Fibrous Tissue

Conversion of granulation tissue into scar

Spindle shaped fibroblasrt

Dense collagen

Vascular regression continues as scar matures

Scar formation

Non-dividing cells hence must heal by fibrosis instead

Neurons

Cardiac muscle

Skeletal muscle

Healing of clean wounds with opposed edges

Immediate response to injury

Wound fills with clotted blood

Dehydration of clot form scab

Acute inflamation occurs with appearance of neutrophils at edge of wound

24-48Hrs

Epidermis at cut edge thickens due to mitotic activity of basal cells

Spurs of epithelial cells migrate and grow along margins

Fusing in midline beneath surface scab

Continuous thin epithelial layer formed

Day 3

Replacement of neutrophils by macrophages

Granulation tissue invades incisional space

Collagen fibers present at margin but do not bridge incision

Epithelial proliferation continues

Day 5

Incisional space filled with granulation tissue

Collagen bridges incision

Epidermis recovers normal thickeness

Week 2

Continued proliferation of fibroblast and accumulation of fibrogen

Leukocyte infiltration, Edema and increased vascularity disappeared

1st Month

Scar comprises of connective tissue covered by intact epidermis

Dermal appendages destroyed by injury are permanently lost

Tensile strength increases gradually thereafter

Occurs in wounds with separated edges

Differences compared to 1st Intention healing

More intense inflammatory rxn

Much larger amounts of grnulation tissue formed

wound contraction present

mediated by myofibroblast

Fibroblast with smooth muscle characteristics

Parenchymal regen cannot fully reconstitute original architecture

Former site of tissue damage and active inflammation

Occupied by

Proliferating capillaries and fibroblast

Wound Healing

Macrophages and lymphocytes

Resolving inflammation

2 patterns

Early form

Vascular granulation tissue

Leukocytes

Proliferating fibroblasts

Loose connective tissue matrix

Late form

Fibrous granulation tissue

Inconspicuous capillaries and numerous plump activated fibroblasts