This document summarizes wound healing and fibrosis. It discusses the processes of granulation tissue formation, angiogenesis, fibrogenesis, and maturation/remodeling that lead to scar formation during wound healing. It describes primary and secondary wound healing. Complications of wound healing like hypertrophic scars, keloids, and chronic ulcers are also outlined. Other examples of fibrosis including thrombus organization, infarct healing, and bone healing are provided. The document also briefly discusses stem cells, their types (totipotent, pluripotent, multipotent), sources, and potential therapeutic applications.

1. REPAIR
By
Shatha al sulh
1

2. Healing By Fibrosis
• Replacement of the damaged tissue by granulation tissue which
matures into fibrous tissue (scar).
• Michanism:
• Start with granulation tissue formation (fibroblasts &
capillaries) moist, red, granular.
• matures to fibrous tissue (collagen deposition
followed by remodeling) firm, greyish.
• Controlled by GF.
• Steps: angiogenesis, fibrogenesis,progressive
maturation & remodeling.
• E.g: healing of wounds, healing of serofibrinous
inflammation & others. 2

3. 3

4. Hypertrophic scars on neck with
raised features within scar margins. 4

5. 5

6. Angiogenesis (neovascularisation)
•Formation of new capillaries.
•Steps:
• Proteolytic degradation of the parent vs. BM migration of
endothelial cells proliferate solid endothelial budds.
• Canalization (maturation) of the budds to form capillary tubes.
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7. Fibrogenesis
• Fibroblast migration, proliferation & secretion of collagen.
• Steps:
• Migration of fibroblasts to the site of injury.
• Proliferation of fibroblasts.
• Secret ECM ptn (fibronectin & proteoglycan).
• Type III collagen (thin fibrils).
• Type I collagen (thick fibrils).
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8. Progressive maturation & remodeling
• To form the permanent scar.
• Steps:
• Resorption of many capillaries
• progressive type I collagen synthesis.
• When the scar is big : Myofibroblasts action.
• Collagenases: minimize the scar size.
• Mature scar :
• Matrix
• dense collagen type I
• few or no capillaries (nearly avascular)
• resting fibrocytes.
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9. Types of wound healing
1ry union
• Type of wound:
• non gaping
• Clean
• with minimal tissue loss
• close edges.
• E.g: stitched surgical wound.
2ry union
• Type of wound:
• Gaping
• Infected
• with marked tissue loss
• widely separated edges.
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10. 1ry union
• Michanism:
a)D1: the narrow wound gap filled with clotted blood& covered with scab of dry clotted
blood.
b)D2:start epid.regen.At both edges from the basal layer with new BM, complete 1-
2d,PMN exudate in wound gap.
c) D3: macrophages replace PMN + phagocytosis & GF.
d)D4&5: granulation tissue starts& fills the gap+ start collagen fibril appear
e)2nd-4th w:
a) Separation of surface scab(end 2nd w) .
b) Maturation of GT to FT.
c) Wound shows fine mature small scar covered by regenerated epidermis.
d) Skin adenexa don’t regenerate.
• Less common complications. 10

11. 11

12. 2ry union
•Michanism: basically similar to 1st intension, but differ in :
a)necrotic debris, clots, inflam.cells> extensive. Pus may exist, phagocytosis take longer
time causing longer period of healing.
b)Epidermal proliferation starts early but fails to reconstitute epid.covering except after
filling the gap with GT so, epid.cells can grow over it to complete epid. regeneration.
c) Amount of GT is > larger,so scar is big.
d)Wound contraction by myofibroblasts.
– Finally the wound consists of contracted scar covered with regenerated epid.
– Skin adenexa don’t regenerate.
•More common complications.
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14. 14

15. 15

16. Healing of wounds (cont.)
• Complications :
• Cosmetic deformities ( extensive scar).
• Functional troubles: contracture of scars round joints.
• Keloid:
• Protuberant scar covered by stretched epidermis.
• Overdone repair (susceptible persons or FB).
• Recure after surgical excision & shrink with irradiation.
• Epidermoid cyst (implantation cyst):
• keratin filled cyst, due to proliferated trapped epith.cells in the depth of the
wound.
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17. 17

18. 18

19. 19

20. • Chronic ulcer, fistula, sinus:
• Chronic ulcer: persistent surface discontinuity due to loss of
epithelium.
• Chronic sinus: persistent blind ended tract, opening to a surface by
single opening.
• Chronic fistula: persistent double ended tract with opening on 2
surfaces.
• Michanism: due to defective repair due to :
• Persistent infection destroy granulation tissue.
• Excess deposition of collagen at wound edges without filling the
whole wound with granulation tissue.
• carcinoma:
• Rarely from the epithelium related to a scar (mainly burn).
• This SCC called Marjolin’s ulcer.
Complications of wound healing (cont.):
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21. Marjolin’s ulcer
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22. Healing of serofibrinous inflam.
• Michanism :
• Absorbtion of fluid exudate & phagocytosis.
• GT (from subserosal tissue).
• Regeneration of serosal cells.
• Maturation of GT to fibrous tissue.
• Complications:
• Extensive fibrosis leading to adhesions (fibrous
extensions between visceral & parietal layers).
• Lead to serious efects e.g intestinal obstruction in
case of peritoneal adhesions.
22

23. Small intestine with Fibrovascular adhesions
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24. Other examples of fibrosis:
• Fibrous organization of thrombi.
• Infarcts.
• Meningitis.
• Arthritis ankyloses (is a stiffness of a joint due to abnormal adhesion and rigidity of the
bones of the joint, which may be the result of injury or disease.The rigidity may be complete or
partial and may be due to inflammation of the tendinous or muscular structures outside the joint or of
the tissues of the joint itself).
• Salpingitis tubal adhesions.
• Fibrous healing of bone. 24

25. 25

26. Stem cells
• Unspecialized cells giving copies of themselves & also develop
into mature cells of different types under proper conditions.
• to repair, treat & cure many diseases.
• Examples of Potential theraputic applications:
• Production of complete organs.
• Generation of HF stem cells to ttt baldness.
• Generation of insulin secreating pancreatic cells to ttt type 1 DM.
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27. Types of stem cells:
• Totipotent, Pluripotent & Multipotent.
• Totipotent:
• In mammals.
• Become any type in adult body, any cell of extraembryonic
memb.
• Include only the zygote & 1st few primitive cells produced by its
division.
• Misnomer.
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28. 28

29. •Pluripotent:
• True stem cells.
• Only From embryonic or fetal tissue.
• Can be grown in specific cultures to reproduce themselves
without differentiation.
• They can make any differentiated cell in the body.
• 3 types:
• Embryonic Stem (ES) cells: from ICM of blastocyst obtained from excess
embryos during IVF.
• Embryonic Germ (GS) cells: from precursor gonadal cells of aborted fetuses.
• Embryonic Carcinoma (EC) cells: from teratocarcinoma, aneuploid cells(unlike
previous 2).
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30. •Multipotent:
• True stem cells:
• Self renewal: make identical copies of themselves.
• Give raise to mature cell types with charecterstic shapes &
specialised functions.
• Differentiate into limited number of types.
• Found in adult animals & most organs contain them to replace dead
or damage cells.
• May give raise to clone of cancer cells(if accumulate sufficient
mutations).
• Progenitor cells : partly differentiated intermediate cell type
produced by multipotent stem cells, committed to particular cell
lineage to give raise to differentiated cells.
• Best e.g hematopoietic SC in BM. 30

31. •Sources of SC:
• Aborted fetuses or fertilized eggs : limited by ethical
considerations.
• BM, peripheral blood or UC blood: ethical & legal.
• Recent sources of adult stem cells: skin, pulp of milk teeth & fat
cells.
•SC plasticity: adult SC from 1 tissue able to give raise to cell types of
a completely different tissue (in contrast to previous believe that adult
SC are irreversibly committed to specific lineages of differentiation).
E.g:BMSC becoming neurons or pancreatic islet cells producing
insulin. 31