Lecture 07 - Regeneration, Scarring, Angiogenesis

Question 1

Extracellular Matrix

Answer 1

1. BMG: epithelium to underlying tissue –> laminin, collagen IV, proteoglycan
2. intercellular matrix –> proteoglycan, fibrillar collagen, elastin, hyaluronic acid

Question 2

Conditions for Regeneration

Answer 2

1. remained tissue

2. existing extracellular matrix

Question 3

Phases of Type 2 Regeneration

Answer 3

1. Priming: TNF –> kupffer –> IL-6 –> hepatocytes –> G0 to G1
2. Proliferation: HGF, FGF, TGF-a –> rest of cycle
3. Growth inhibition: TGF-b, Activin

Question 4

Scarring

Answer 4

1. permanent tissue damage
2. injury to extracellular matrix or germinal pool
3. angiogenesis –> a day
4. granulation tissue: scattered collagen by fibroblasts, undone walls (edema), mononuclear chronic inflammation –> 3-5 days
5. maturation: clear cellular debris, collagen III to I –> 8-365 days

Question 5

Angiogenesis Process (1st hypothesis)

Answer 5

1. dilation and increased vascular permeability by VEGF
2. Dilation by NO
3. BMG destruction by metaloproteins
4. breaking intercellular junctions by TPA
5. chemotaxis and migration of endothelium
6. endothelium proliferation
7. pericyte and SM placement

Question 6

Angiogenesis Process (2nd hypothesis)

Answer 6

by EPC

Question 7

Angiogenesis GFs

Answer 7

VEGF A: by mesenchymal and stromal cells, attaches to receptor II –> angiogenesis
FGF-2: proliferation, differentiation and migration of endothelial cells

Question 8

Skin Regeneration

Answer 8

primary union:
- day 1,2: sutured and filled with blood clot, neutrophil aggregation, basal cells mitosis (horizontal and vertical)
- day 3: macrophage aggreagtion, granulation
- day 5: most of granulation, collagen bridging, remodeling, epiderm complete
- 2nd week: more collagen, less granulation, blanching
Secondary union: in case of disability of basal cells to reach each other –> 1. Cutaneous flap 2. Wound contraction (malformation, thin epiderm) –> fibroblast and myofibroblast(mostly) close the wounds

Question 9

Skin Regeneration Comparison

Answer 9

1. Primary union:
   - no sepsis
   - minimum tissue loss
   - no contraction
   - minimum granulation
2. Secondary union:
   - possible sepsis
   - considerable tissue loss
   - contraction
   - maximum granulation

Question 10

Pathologic Regeneration

Answer 10

1. Contracture –> tumor-like granule

2. High/low scar formation

Question 11

Causes of Low Scar Formation

Answer 11

Local:
1. Infection
2. Mechanical stress
3. Foreign object
4. Location of wound
5. Type of wound
Systemic:
1. Malnutrition: low protein, vit C and Zn
2. Metabolic defects: low regeneration –> diabetes
3. Blood supply defects –> atherosclerosis, venous stasis
4. Steroidal hormones: regeneration synthesis inhibition –> couching’s
5. Chemotherapy –> mitosis inhibition
6. Radiotherapy
7. Aging

Question 12

Look of Low Scar Formation

Answer 12

1. Ulceration: low blood supply and innervation –> bed sore

2. Dehiscence: mechanical factors, infection –> abdominal surgery

Question 13

Causes of High Scar Formation

Answer 13

1. Hypertrophic scar:
   - High collagen synthesis –> malnutrition, high tension
   - sclerosis
   - prominence
   - pink
   - limited to the wound
   - collagen correct formation
2. Keloid:
   - common among black
   - high collagen synthesis
   - unlimited and invasive
   - incorrect collagen formation
   - uncontrollable
3. Proud Flesh: high granulation