Tissue repair occurs through either regeneration or scar formation. Regeneration involves the proliferation of residual cells to completely restore lost tissue, while scar formation deposits connective tissue when regeneration is not possible. The key stages of wound healing are inflammation, proliferation, granulation tissue formation, wound contraction, and strength acquisition. Factors like nutrition, infection, and location can influence healing. Complications include deficient or excessive scarring, contractures, and exuberant granulation. Stem cells also contribute to tissue repair through self-renewal and generation of new cells.

1. Item- 08
Tissue Repair
Dr. A K M Maruf Raza
Associate Professor of Pathology
Based on Robbins and Cotran
9th edition

2. Tissue Repair/Healing
• Repair, sometimes called healing refers to the
restoration of tissue architecture and function after an
injury.
• Repair of damaged tissues occurs by two types of
reactions:
1. Regeneration.
2. Connective tissue deposition (scar formation).

3. Tissue Repair/Healing
• Regeneration: is complete restitution of lost tissue
components identical to those removed or killed by
proliferation of residual (uninjured) cells and
maturation of tissue stem cells.
• Connective tissue deposition (scar formation): If the
injured tissues are incapable of regeneration, or if the
the tissue is severely damaged, repair occurs by the
deposition of connective tissue.

4. Tissue Repair/Healing
• Regeneration occurs for example, in the rapidly
dividing epithelia of the skin and intestines, and in
some parenchymal organs, notably the liver.
• Scar formation takes place in fibrosis of the lungs,
liver, kidney and in Myocardial Infarction.

5. Tissue Repair/Healing

6. Components of wound healing
1. Inflammation.

2. Proliferation and migration of parenchymal and
connective tissue cells.

3. Formation of granulation tissue.

4. Wound contraction.

5. Acquisition of wound strength.

7. Tissue Repair/Healing

8. Tissue Regeneration
• Both regeneration and scar formation contribute in
varying degrees to the ultimate repair.
• Both processes involve the proliferation of various
cells, and close interactions between cells and the
extracellular matrix (ECM).
• The cell proliferation in regeneration and repair is
driven by growth factors (VEGF, TNF, PDGF, TGF).

9. Tissue proliferative activity
1.Continually dividing cells (labile tissues):
These cells proliferate through-out life.
Epithelium of the skin, GIT and cells of bone marrow.
2.Quiescent cells (Stable tissue):
Have a low level of replication. Cells from these tissue
can undergo rapid division in response to stimuli.
parenchymal cells of liver and kidneys.
3.Non-dividing (permanent cells):
Cells that can not undergo mitotic division in the post-
natal life. Neurons and cardiac muscle cells.

10. Granulation tissue
• Granulation tissue is the hallmark of healing.
Granulation tissue progressively invades the site of
injury.
• The term granulation tissue derives from its pink,
soft, granular appearance seen an area of going
wound healing.

11. Granulation tissue
• Granulation tissue is:
i. the proliferation of fibroblasts
ii. new thin-walled, delicate capillaries
(angiogenesis), in a loose extracellular
matrix.
iii. admixed inflammatory cells, mainly
macrophages.

12. Granulation tissue

13. Healing of skin wound
• Healing of skin wound is a process that involves
both epithelial regeneration and the formation of
connective tissue scar.
• Based on the nature and size of the wound, the
healing of skin wounds occurs by first or second
intention.

14. Healing of skin wound
Healing by first intension
• When the injury involves only the epithelial layer
and the principal mechanism of repair is epithelial
regeneration it is called primary union or healing
by first intention.
• It is the process of healing of a clean, uninfected
surgical incisions approximated by sutures.

15. Healing by second intension
• Healing by second intention is also known as
healing by secondary union.
• When cell or tissue loss is more extensive like in
large wounds, abscesses, ulceration, and ischemic
necrosis (infarction) in parenchymal organs.
• The repair process in second intension involves a
combination of regeneration and scar formation.

16. Difference between
Primary intension
1. Inflammatory reaction is
less marked.
2. No wound contraction.
3. Margins are apposed
together.
4. Minimal tissue damage
5. Minimal bleeding
6. Heals quickly
7. Small scar.
Secondary intension
1. Intense inflammation.
2. Much granulation tissue
formation.
3. Gap persists between
margins.
4. Marked damage of
tissues.
5. More bleeding.
6. Takes time to heal.
7. Large scar

17. Healing by first VS second intension

18. Factors influencing wound healing
Systemic factors:
1.Nutritional status: Protein deficiency and vitamin C
deficiency inhibit collagen synthesis and delay wound
healing.
2.Metabolic status: DM is associated delay in wound
healing.
3.Circulatory status, poor perfusion: Inadequate blood
supply impair wound healing.
4.Hormones: Glucocorticoids have anti- inflammatory
effects and inhibits collagen synthesis causing delay.

19. Factors influencing wound healing
Local factors:
1.Infection (one of the most important cause of delay
in healing).
2.Mechanical factors (increased local pressure, high
mobility delays healing).
3.Foreign bodies (splinter, steel, glass delays healing).
4.Size and shape of wound (clear cut surgical wound
heals quickly).
5.Location of the wound (wound in the face heals
quickly)

20. Complications of wound healing
Complications of wound healing are grouped into
three categories:
i. Deficient scar formation.
ii. Excessive scar formation.
iii. Exuberant granulation tissue formation
iv. Formation of contractures.

21. Complications of wound healing
Deficient scar formation can lead to two types of
complications:
1.Dehiscence or rupture of a wound.
2. Ulceration.
Wound dehiscence is common after abdominal
surgery and is due to increased abdominal
pressure.
Wounds ulceration is due to inadequate
vascularization. Example lower extremity wounds
in with atherosclerosis.

22. Complications of wound healing
Excessive scar formation can give rise to:
(1) hypertrophic scar
(2) keloids.
• The accumulation of excessive amounts of
collagen give rise to a hypertrophic scar.
• If the scar tissue grows beyond the boundaries of
original wound and does not regress, it is called
keloid.

23. Keloid

24. Exuberant granulation tissue
• Exuberant granulation is the formation of
excessive amounts of granulation tissue, which
protrudes above the level of the surrounding skin
and blocks re-epithelialization (proud flesh).
• Excessive granulation must be removed by cautery
or surgical excision to allow re-epithelialization.

25. Wound Contracture
• An exaggeration of contraction of wound gives rise
to contracture and results in deformities of the
wound and the surrounding tissues.
• Common areas affected palms, the soles and the
anterior aspect of the thorax.
• Contractures are commonly seen after serious
burns which compromise movement of joints.

26. Wound Contracture

27. Remodeling of Connective Tissue
• The outcome of the repair is influenced by a balance
between synthesis and degradation of ECM proteins.
• The connective tissue in the scar continues to be
modified and remodeled.
• Scar modified and remodeled by an enzyme called
matrix metalloproteinases (MMPs) produced by a
variety of cell types (fibroblasts, macrophages,
neutrophils.

28. Stem cell
• Stem cell is characterized by prolonged self renewal
capacity .
Embryonic Stem cells:
Are pluripotent that is they can generate all tissues of
the body.
Adult Stem Cells:
1. Bone marrow stem cells
2. Skin  hair follicle bulge, inter-follicular area and
sebaceous glands

29. Thank you all