Tissue repair

1. Yi-Che, William, Chang Chien, MD, PhD
Tissue regeneration,
reparation,
wound healing
& calcification

2. Fibrosis
persistent (chronic damage)
Reparation
(incomplete restoration)
More severe acute injury
Wound healing
scar
Injury
Regeneration
(complete restoration)
Minor acute injury
No scar
Fate after Tissue Injury

3. Regeneration vs Reparation
• Regeneration:
(near) complete replacement of injured cells by normal ones (skin, gut
epithelium; liver)
• Reparation (scar formation):
if damage and tissue destruction is more severe Functionally not active; provides
structural stability
• Extracellular matrix – cell interactions are crucial

4. Cells involved in reparation
(repair/healing)
Parenchymal cells (epithelial cells etc.)
Stromal cells:
•Endothelial cells
•Fibroblasts
•Inflammatory cells
• Cellular proliferation is driven by growth factors
•Extracellular matrix is a key component in
the regenerative process

5. Cell proliferation and repair:
Cell population fates
• PROLIFERATION
– Hormonal, especially steroid hormones
– eg., Erythropoietin (EPO), CSF
• DIFFERENTIATION/DEDIFFERENTIATION
– UNIDIRECTIONAL, GAIN and LOSS
• CELL DEATH (APOPTOSIS VS NECROSIS)

6. Different proliferative capacities
• labile cells - epithelial, haematopoietic
• stabile cells - liver, kidney, pancreas, endothelia,
muscle - limited regeneration capacity
• permanent cells - neuron, cardiac muscle
- no regeneration

7. Growth factors
in regeneration & repair

8. Steps in reparation– basic facts

9. Reparation –
basic steps
• FOLLOWS INFLAMMATION 
• PROLIFERATION and MIGRATION of
connective tissue cells
• ANGIOGENESIS (Neovascularization)
• Collagen, other ECM protein synthesis
• Tissue Remodeling
• Wound contraction
• Increase in wound strength (scar)

10. Granulation tissue
Mature scar
(Trichrome stain)


11. Angiogenesis and repair
(NEOVASCULARIZATION)
• From endothelial precursor cells (EPC)
• Mainly from PREexisting vessels
• Stimulated/Regulated by GF’s,
especially VEGF
• Also regulated by ECM proteins
• Contributes to GRANULATION TISSUE

12. Angiogenesis from pre-existing vessels vs
from bone marrow derived EPCs

13. Extracellular matrix in Repair

14. Skin: Types of wound healing
Wound healing
• Edges lined up
• 1st INTENTION • 2nd INTENTION
• Edges NOT lined up
• More granulation
• More epithelialization
• More FIBROSIS
e.x.: surgical wound
e.x.: accidental trauma

15. Phases of wound healing
macrophage,
endothelium
neutrophils
fibroblasts

16. An example of 2° wound healing:
Skin ulcer

17. RETARDING factors of wound healing
(LOCAL)
• DECREASED Blood supply
• Type, size, location of the wound (back, sacrum)
• Ionizing radiation, UV light (further damaging)
• Denervation
• Local Infection
• Hematoma,Mechanical stress, Necrotic tissue

18. RETARDING factors of wound healing
(SYSTEMIC)
• DECREASED Blood supply
• Age
• Anemia
• Malignancy
• Malnutrition
• Metabolic status (Diabetes)
• Hormones (cortisol)
• Obesity
• Systemic infection (sepsis)
• Organ failure

19. Abnormal wound healing:
keloid(‘too much collagen’)

20. Fibrosis
• DEPOSITION OF COLLAGEN by FIBROBLASTS
• With time (weeks, months, years?) the collagen becomes
more dense, therefore, the tissue becomes
“STRONGER”
contracture:
(too much fibrosis & wound contraction)

21. Fibrosis regulated by cytokines

22. Definitions:
• abnormal deposition of calcium salts (usually with
Fe++(+), Mg++ and other minerals)
• dystrophic calcification: in dying, degenerating tissues
with normal calcium metabolism (DNA lacks of phosphate backbone,
negatively charged)
• metastatic calcification: deposition in normal tissue,
due to derangement in Ca++ metabolism
(hypercalcaemia, parathyroid homone, tumor necrosis)

23. Dystrophic calcification
•previous tissue injury
•initiation (or nucleation): calcium enters cells  binds
to phospholipids of membranes, vesicles, mitochondria
• propagation (calcium phosphate deposition): focus
of nucleation grows (gritty, sand-like or stone-hard
mass)
• source of calcium: interstitial fluid, blood
• inhibitors and promoters of mineralisation (pH, etc.)

24. Examples of dystrophic calcification
• Degenerated cyst
• heart valves
• in necrosis (infarct, TB, lymph nodes, pancreas)
• in thrombi
• tumours
• metaplastic bone formation may occur (ossification)

25. Metastatic calcification
• increased parathormon: parathyroid tumour
• bone destruction. Increased turnover (Paget disease);
• tumours (multiple myeloma, leukaemia);
• Vitamin-D intoxication
• renal failure with phosphate retention
 2° hyperparathyroidism
• sites: lung (alveolar septa); stomach; kidney.