This ppt will give you an understanding about tissue repair via regeneration and scar formation.

1. Basic Pathology
Lecture 4
Tissue Repairs and Healing
By Hermizan Halihanafiah

2. Introduction to Tissue Repair
• Tissue repair refers to the restoration of tissue
structure and function after injury.
• It can be :
1. Regeneration: replacement of injured parenchymal
cells with cells of the same type
2. Connective tissue (fibrous tissue) replacement :
lead to the scar formation (fibrosis)

3. Tissue Repairs
• Involve cell proliferation, differentiation and
apoptosis
• Cell proliferation :
• Cell Differentiation :
• Cell apoptosis :

4. Continue….
• Several types of cells proliferate during tissue
repair including remnants of injured
parenchymal cells, vascular endothelial cells
fibroblast.
• The proliferation of this cells driven by protein
known as growth factors, hormones, cytokines
• It also mediates for cells growth. For examples
IGF stimulates hypertrophy of skeletal
muscles.

5. Cell Cycle
• Full regeneration or repair cannot occur without
replacing cells lost (due to injury or disease) through
the cell cycle
• Cell cycle consist of several steps
– Synthesis (S)
– Mitosis (M)
– Gaps 1 (G1)
– Gaps 2 (G2)
– Gaps 0 (G0)

6. CELL CYCLE

7. PROLIFERATIVE CAPACITY OF TISSUE
• The capacity for regeneration varies with
tissue and cell type
• Based on the ability of their parenchymal cells
to undergo regeneration, body tissue can be
divided into:
– Labile tissue/cells
– Stable tissue/cells
– Permanent tissue/cells

8. Labile tissues
• Cells continue to divide
and replicate
throughout
life, replacing
injured/destroyed cells
• Examples: epithelium
cells of skin, GIT, vagina
etc

9. Stable Tissues
• Cells that normally stop dividing when growth
ceases.
• This cells remain in G0 phase in cell cycle, but
capable to undergo regeneration with
appropriate stimulus.
• Examples : liver, kidney, smooth muscles
cells, vascular endothelium.

10. Permanent Cells
• Do not proliferate
• Considered terminally
differentiated (highly
specialize)
• Do not undergo mitotic
division in postnatal life.
• Example: nerve
cells, skeletal muscle
cells, cardiac cells
• Once destroyed, it will
replaced by fibrous
connective tissue (scar
formation)

11. Extracellular Matrix and Cell Matrix Interaction
• ECM – network of spaces
surrounding the tissue
cells
• 3 basic components of
ECF
– Fibrous structural
protein (collagen and
elastin fiber)
– Water hydrated gel
(proteoglycans and
hyaluronic acid)
– Adhesive glycoprotein
(fibronectin, laminin)

12. Healing by Connective Tissue Repair
(Fibrosis Formation)
• Tissue repair highly associated with tissue
regeneration – replacing the injured/destroyed
cells with the same type cells
• Tissue regeneration only occur in labile and stable
cells
• If the regeneration cant occur, healing process via
fibrosis formation (scar formation)
• Fibrosis – extensive the deposition of collagen
fiber (lungs, kidney, liver etc) as a results of
chronic inflammation or injury

13. Fibrosis Formation
4 basic processes:
• In growth of granulation tissue and Formation
of new blood vessels (angiogenesis)
• Migration and proliferation of fibroblast and
Deposition of ECM
• Maturation and reorganization of the fibrous
tissue (remodeling)

14. Ingrowths of granulation tissue
• Formation of granulation tissue at the site of
injury area
• Granulation tissue : highly vascularized tissue,
composed with newly formed capillaries,
proliferating fibroblast and residual inflammatory
cells.
• Vascular proliferation, fibroblast and other cells
at the site of injury is controlled by growth
stimulatory and inhibitory factors (most
importantly Vascular Endothelial Cells Growth
Factor & Fibroblast Growth Factor)
• Edamotous appearance – leaking of new blood
vessels

15. Migration and proliferation of fibroblast and
deposition of ECM
• Migration and proliferation of fibroblast at the
injury site driven by platelet derived growth
factor (PDGF)
• Collagen fiber synthesis by fibroblast, is critical
to the development of strength in a healing
site (days 3 – 5) and may continue to several
weeks
• Granulation tissue ------- scar tissue

16. Maturation and reorganization of the fibrous
tissue (remodeling)
• the collagen content of granulation tissue
progressively increase in time
• A young scar tissue consist of granulation
tissues, collagen fiber and moderate number
of capillaries and fibroblast
• As the scar matures, the amount of collagen
increases and the scar become less cellular
and vascular.

17. Healing of Epithelium Tissue
(Wound Healing)
• Involve epithelial cells regeneration and scar formation
• Wound healing mechanism can be divided into two ways:
1. Healing by first intention (primary union)
• Simple repair, clean incised wound and laceration in
which the edges of the wound are in close apposition.
2. Healing by second intention (secondary union)
• When the wound can’t be heals by 1st intention
• Large wound or Tissue lost more extensive
• Maybe due to infarction, inflammatory ulceration,
abscess formation, infections.

18. Wound Healing Mechanism
• Cutaneous wound healing commonly can be
divided into three phases
1. Inflammatory phase
2. Proliferative phase
3. Remodeling / maturational phase

19. Inflammatory Phase
• Crucial period – it prepares suitable environment for
tissue healing
• Hemostasis : constriction of injured blood
vessels, blood clot formation with platelet
aggregation
• Then vasodilatation, and increase it’s permeability
allowing blood plasma and its component to leak
into injured area.
• Then follows by cellular phase ; migration of
phagocytic WBC (neutrophil and macrophage)
• Macrophage : release of growth factor – promote
epithelial cell growth, angiogenesis and attraction of
fibroblast

20. Proliferative Phase
• The major cells during this phase : fibroblast
• Synthesizes and secretes collagen and other
intercellular elements that needed for wound
healing’
• Fibroblast also produce growth factor (FGF) that
needed for angiogenesis, wound contraction and
matrix deposition.
• Fibroblast and vascular epithelial cells begin
proliferating and form granulation tissue that
serves as the foundation for scar tissue
development.

21. Continue…
• The final component of proliferation phase is
epithelialization, which is the
migration, proliferation and differentiation of
epithelial cells and the wound edges.

22. Remodeling Phase
• Begins approximately 3 weeks after injury and continue
for 6 months or maybe longer
• There is continued remodeling of scar tissue by
synthesis of collagen by fibroblast and lysis by
collagenase enzyme.
• As a results the architecture of the scar become
reoriented to increase the tensile strength of the
wound
• An abnormality in healing by scar tissue repair is keloid
formation
• Keloid are benign tumorlike masses caused by excess
production of scar tissue (excessive collagen).

25. Factor That Affect Wound Healing
• Failure of collagen synthesis
• Excessive collagen production – keloid formation
• Local factors :
– Foreign or necrotic tissue or blood
– Infections
– Abnormal blood supply (ischemic)
– Decrease viability of cells – irradiation of the
tissue/antimitotic drugs
• Diabetes mellitus – poor microcirculation / infections
incidence
• Excessive levels of adrenal corticosteroid (depress WBC
function)

26. Bone Healing/repairs
• The repair of the bone fracture involves the
following steps:
1. Formation of fracture hematoma
2. Fibrocartilaginous callus formation
3. Bony callus formation
4. Bone remodelling

27. 1.Formation of fracture hematoma
• Haemorrhage within
the bone from ruptured
blood vessels and
forming blood clot - - - - -haematoma
• Haematoma facilitates
repair and tissue
healing
• Forms 6-8 hours after
injury

28. 2. Fibrocartilaginous callus formation
(soft tissue callus)
• Formation of collagen
fiber by fibroblast and
fibrocartilage by
chondroblast
• Lead to formation of
fibrocartilaginous
callus and become
bridge of the broken
area

29. 3. Bony callus formation
• Ossification --conversation of
fibrocartilaginous callus
into bony callus
• Osteogenic cells
developed into
osteoblast and then
developed into spongy
bone trabeculae
• Begins 3 – 4 weeks after
injury

30. 4. Bone remodelling
• Final phase
• Remodeling of the
bony callus
• Compact bone replace
by spongy bone at the
periphery site
• Osteoclast – resorps
the fragment of broken
bone

31. Factors That Influence Bone Healing
1. Malunion
• Healing with deformity at fracture site
• Inadequate reduction or malalignment of
fracture at time of mobilization

32. 2. Delayed union
• Failure to unite within normal period
• Contributing factors:
– Large displaced fracture
– Inadequate immobilization
– Large hematoma
– Infection at fracture site
– Excessive lost of bone
– Inadequate circulation

33. 3. Nonunion
• Failure to produce union / cessation of bone
repairs process
• Contributing factors:
–
–
–
–
–
–
–
–
–
Inadequate reduction
Mobility at fracture site
Severe trauma
Soft tissue between bone fragment
Infection
Extensive loss of bone
Inadequate circulation
Malignancy
Bone necrosis