Healing and Repair

Question 1

What are the 4 stages of healing in soft tissues?

Answer 1

1) Clotting phase
2) Inflammation phase
3) Proliferative phase
4) Maturation phase

Question 2

What does acute inflammation result in?

Answer 2

The complete restoration of tissues

Failure of resolution -> chronic inflammation

Question 3

What is the difference between regeneration (resolution) and repair?

Answer 3

Regeneration = replacement with functional differentiated cells (acute inflammation leads to this)
Repair = production of a fibrous scar and changes in tissue structure/architecture

Question 4

What are ‘labile cells’?

Answer 4

Cells in which normal state is activate cell division
Rapid regeneration
e.g. oral keratinocytes

Question 5

What are ‘stable cells’?

Answer 5

Conditional renewal cells
Variable rates of regeneration
Rapid proliferation in response to injury
e.g. oral fibroblasts

Question 6

What are ‘permanent cells’?

Answer 6

Unable to divide
Unable to regenerate
e.g. nerve fibres

Question 7

What happens during the clotting phase of healing? (in soft tissues)

Answer 7

Clot formation by the coagulation system

Mitosis of labile/stable cells

Question 8

What happens during the inflammation phase of healing? (in soft tissues)

Answer 8

Macrophages/neutrophils phagocytose and degrade infectious agent
Stimulation of certain cells (e.g. keratinocytes, fibroblasts) to start regenerating and/or repairing tissue

Question 9

What happens during the proliferative phase of healing? (in soft tissues)

Answer 9

Formation of granulation tissue
Fibroblasts are key players
New connective tissue laid down, rich in collagen
Angiogenesis (formation of new blood vessels)
Growth factors are essential

Question 10

Describe vascular granulation tissue (i.e. the first phase of granulation tissue during the proliferative phase of soft tissue healing)

Answer 10

Mix of proliferating capillaries, fibroblasts, immune cells

New capillaries are relatively ‘leaky’ allowing cells and fluid into tissue

Question 11

Describe fibrous granulation tissue (i.e. the second phase of granulation tissue during the proliferative phase of soft tissue healing)

Answer 11

Capillaries regress and immune cells return to the blood

Mature fibroblasts lay down collagen

Question 12

What is the difference between the first and second phase of granulation tissue?

Answer 12

First phase: vascular granulation tissue. Tissue is highly vascularised. Allows flow of immune cells

Second phase: consists more of fibrous tissue. Fibroblasts lay down collagen

Question 13

Describe angiogenesis

Answer 13

Occurs during the proliferative phase of soft tissue healing
New blood vessels formed from existing vasculature by sprouting or splitting
Driven by VEGF

Question 14

What is VEGF?

Answer 14

Vascular endothelial growth factor. Drives angiogenesis.

Question 15

What is VEGF produced by?

Answer 15

Epithelial cells, macrophages and fibroblasts

Question 16

What is the role of growth factors in tissue healing?

Answer 16

Promote or inhibit cell growth and differentiation

Question 17

Give some examples of growth factors in tissue healing.

Answer 17

Cytokines and hormones are growth factors.
VEGF - angiogenesis
TGF-beta - stimulates fibroblast proliferation and collagen synthesis
EGF - regeneration of epithelial cells

Question 18

What happens if the balance of growth factors is disturbed?

Answer 18

Dysregulated cell proliferation and survival of abnormal cells

Question 19

What are the functions of growth factors?

Answer 19

Promote cell survival
Locomotion 
Contractility 
Differentiation 
Angiogenesis

Question 20

What does fibrosis mean?

Answer 20

The extensive deposition of collagen and formation of excess fibrous connective tissue

Question 21

Which cells drive fibrosis?

Answer 21

Fibroblasts and macrophages

Question 22

When does fibrosis occur?

Answer 22

Following substantial or repeated damage e.g. in chronic inflammation

Question 23

What is the role of M2 macrophages?

Answer 23

They are essential in the process of healing and repair
Engulf/degrade
Produce growth factors (VEGF, TGF-beta, EGF, PDGF)

Question 24

What happens during the maturation phase of soft tissue healing?

Answer 24

Disorganised granulation tissue is remodelled by remaining cells
Collagen fibres are cross linked across tension lines
Re-epithelization (growth factors)
Regain of tensile strength
Fibrous scar remains (in repair)
Tissue remodelling

Question 25

What does healing by ‘primary intention’ refer to?

Answer 25

Leads to regeneration. This occurs when there is minimal tissue damage. Occurs in acute inflammation

Question 26

What does healing by ‘secondary intention’ refer to?

Answer 26

Leads to regeneration and repair. Inflammation is more intense as there is more necrotic debris, exudate and fibrin to remove. Larger amounts of granulation tissue. Leaves a scar. Longer repair and healing time.

Question 27

What are the 3 stages involved in fracture healing?

Answer 27

1. Inflammatory stage
2. Repairing stage
3. Remodelling stage

Question 28

What happens during the inflammatory stage in fracture healing?

Answer 28

A hematoma is formed (blood clot within tissue) at fracture
Occurs within 48 hours
Acute inflammatory response
Bone cells deprived of oxygen
Blood supply dies off

Question 29

What happens during the first phase of the repairing stage in fracture healing?

Answer 29

Capillaries form in the hematoma 
Occurs within weeks
Fibroblasts produce collagen
Osteoblasts produce spongy bone
Granulation tissue forms and becomes fibrocartilage callus (soft callus)

Question 30

What happens during the second phase of the repairing stage in fracture healing?

Answer 30

Occurs within months
Chondrocytes and osteoblasts produce cartilage and bone
Remaining granulation tissue is ossified
Formation of hard bone at fracture site (fracture callus/woven bone)

Question 31

Whether a fracture heals by regeneration or repair depends on what?

Answer 31

The extent of the fracture determines the outcome - i.e. whether it heals by repair or regeneration