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Tissue Renewal,
Regeneration & Repair
BY:
Dr/ Rehab M. Sharaf, MD
Healing occurs after any insult that causes tissue
destruction, and is essential for the survival of the
organism.
Healing
Regeneration
Proliferation of cells and
tissues to replace lost
structures
Repair
Consists of a combination of
regeneration and scar formation by
deposition of collagen
We have to know:-
 Cell cycle
 Types of Cells in our body.
 The role of Growth factors, Cell to cell and cell to matrix
interactions.
 Angiogenesis.
 Extracellular matrix synthesis and Cell Matrix Interaction.
Cell cycle
The whole process is divided into
three major stages:
1. Mitosis
2. Cytokinesis
3. Interphase
A) Types of cells according to their regenerative
capability
1-Labile cells
• continuously dividing
cells
• replaced by
regeneration
• Examples: -
Stratified squamous
epithelium of skin &
mucous membranes.
2-Stable cells
• quiescent cells (G0).
• enter cell cycle and
divide on demand
• replaced by
regeneration or
fibrosis.
Examples:
Parenchymatous cells
Mesenchymal cells
3-Permanent cells
• Not replaced.
• Regeneration does not
occur.
• repaired by connective
tissue
• Examples:
-Skeletal and cardiac
muscles
- CNS neurons
A) Types of cells according to their regenerative capability
4- Stem cells
 Stem cells are blank unspecialized cells.
 All stem cells have unique general properties:
 Replicate many times throughout the life of the organism.
 Self Renewal
 Stem cells can also divide and become differentiated
 Recently they are used in replacing damaged tissue,
Cell
proliferatio
n
Growth
inhibitors
Growth
stimulator
s
B) Growth factors
B) Growth factors
Growth stimulating factors
1. Epidermal growth factor (EGF):
mitogenic for a variety of
epithelial cells and fibroblasts in
vitro.
2. Platelet-derived Growth Factor
(PDGF): proliferation and
migration of fibroblasts and
smooth muscle cells.
3. Fibroblast Growth Factors
(FGFs): stimulate the
proliferation of fibroblasts and
angiogenesis.
4. Transforming Growth Factor Alpha
(similar to EGF)
5. Transforming Growth Factor Beta.
6. Vascular endothelial growth factor
(VEGF): promotes angiogenesis.
7. Interleukin-1 (IL-1) and Tumor
Necrosis Factor: TNF stimulates
fibroblastic proliferation.
B) Growth factors
Growth Inhibitors
1. Transforming growth factor beta: It inhibits growth in most cell
types; however, it stimulates fibroblast and the production of
collagen and fibronectin.
2. Alpha interferon.
3. Cell to Cell contact inhibition signals
C) Extracellular matrix synthesis and Cell Matrix Interaction
 The extracellular matrix (ECM) is a collection of extracellular molecules secreted by cells that
provides structural and biochemical support to the surrounding cells
ECM components
Structural
Proteins
Adhesive
glycoproteins
Proteoglycans
Functions of ECM
It does much more than just fill the spaces
around cells to maintain tissue structure.
Regeneration
Regeneration is proliferation of residual cells to replace the
lost structures
Regeneration involves
 Cell proliferation, (driven by growth factors )
 Integrated extracellular matrix, and
 development of mature cells
Repair by fibrosis
 The main healing process is repair by deposition of collagen and other
ECM components  SCAR.
 In contrast to regeneration which involves the restitution of tissue
components, repair is a fibro-proliferative response that “patches”
rather than restores the tissue.
Repair by fibrosis
Stages:
1. Inflammation
2. Angiogenesis
3. Migration and proliferation of fibroblasts
4. Deposition of extracellular matrix
5. Organization of collagen “remodeling”
6. Fibrosis – scar formation.
Angiogenesis
Definition:
 Angiogenesis is the process of new blood vessel formation, from
a preexisting vessel.
 VEGF is the most important growth factor involved in physiologic
angiogenesis as well as angiogenesis occurring in chronic
inflammation, wound healing and tumors.
Steps of Angiogenesis
Granulation Tissue
 Granulation tissue is the hallmark of tissue repair
 Characters:-
1. Red granular
2. Soft, Moist
3. Bleeds easily
Granulation Tissue
 Microscopically:
It is Formed of neo capillaries,
extracellular matrix with
fibroblasts +/- necrotic tissue
and scattered inflammatory
cells; macrophages.
Repair of nervous system
 No regeneration can occur.
 The necrotic cells are removed by microglia and then
replaced by proliferation of glial cells.
 This process is called gliosis.
Healing of wounds
Healing by primary union
(1st intention)
Wound characteristics:
 Non-gaping, clean (non
infected), with minimal tissue
loss and approximated edges.
Examples:
 Stitched surgical wound
Healing by secondary union
(2nd intention)
Wound characteristics:
 Gaping and infected wound
with marked tissue loss and
widely separated edges.
Examples:
 Abscess, ulcer, ……..
Stages of wound healing
1. Clot formation
2. Granulation tissue
3. Epithelialization
4. Collagen Formation
5. Scar
6. Maturation of scar
Healing by 2nd intention
Healing by first intention
Features
Gaping wound
Non-gaping wound
Type of wound
Present
Usually not present
Infection
Larger amount
Scanty
The amount of granulation
tissue
Longer time
Short
Healing period
The gap can’t be directly
bridged
Direct (bridge) healing
Healing direction
A prominent feature
Generally not a feature
Wound contraction
Bigger and contracted scar
Thin linear scar
The outcome
Frequent
Infrequent
Complications
Factors That Influence Wound Healing
Systemic Factors
• Nutrition: e.g, vitamin C
deficiency.
• Metabolic status: DM is
associated with delayed healing
• Circulatory status
• Hormones such as
glucocorticoids have anti-
inflammatory inhibit collagen
synthesis.
Local Factors
• Infection
• Mechanical factors,
• Foreign bodies,
• Size, location, and type of
wound.
Complications of wound healing
1. Cosmetic Deformities due to extensive scarring
2. Contracture : an exaggerated wound contraction
3. Function loss e.g. due to contracture of scars around joints.
4. Keloid: exuberant scar protruding on the surface.
Complications of wound healing
5. Chronic Ulcer: loss of epithelial continuity.
6. Sinus: blind ended tract, opening to a surface by a single opening
7. Fistula(an opening tract between 2 hollow organs).
8. Implantation epidermoid cyst.
9. Rarely carcinoma.
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repair for recording (tissue repair) .pptx

  • 1. Tissue Renewal, Regeneration & Repair BY: Dr/ Rehab M. Sharaf, MD
  • 2. Healing occurs after any insult that causes tissue destruction, and is essential for the survival of the organism. Healing Regeneration Proliferation of cells and tissues to replace lost structures Repair Consists of a combination of regeneration and scar formation by deposition of collagen
  • 3. We have to know:-  Cell cycle  Types of Cells in our body.  The role of Growth factors, Cell to cell and cell to matrix interactions.  Angiogenesis.  Extracellular matrix synthesis and Cell Matrix Interaction.
  • 4. Cell cycle The whole process is divided into three major stages: 1. Mitosis 2. Cytokinesis 3. Interphase
  • 5. A) Types of cells according to their regenerative capability 1-Labile cells • continuously dividing cells • replaced by regeneration • Examples: - Stratified squamous epithelium of skin & mucous membranes. 2-Stable cells • quiescent cells (G0). • enter cell cycle and divide on demand • replaced by regeneration or fibrosis. Examples: Parenchymatous cells Mesenchymal cells 3-Permanent cells • Not replaced. • Regeneration does not occur. • repaired by connective tissue • Examples: -Skeletal and cardiac muscles - CNS neurons
  • 6. A) Types of cells according to their regenerative capability 4- Stem cells  Stem cells are blank unspecialized cells.  All stem cells have unique general properties:  Replicate many times throughout the life of the organism.  Self Renewal  Stem cells can also divide and become differentiated  Recently they are used in replacing damaged tissue,
  • 8. B) Growth factors Growth stimulating factors 1. Epidermal growth factor (EGF): mitogenic for a variety of epithelial cells and fibroblasts in vitro. 2. Platelet-derived Growth Factor (PDGF): proliferation and migration of fibroblasts and smooth muscle cells. 3. Fibroblast Growth Factors (FGFs): stimulate the proliferation of fibroblasts and angiogenesis. 4. Transforming Growth Factor Alpha (similar to EGF) 5. Transforming Growth Factor Beta. 6. Vascular endothelial growth factor (VEGF): promotes angiogenesis. 7. Interleukin-1 (IL-1) and Tumor Necrosis Factor: TNF stimulates fibroblastic proliferation.
  • 9. B) Growth factors Growth Inhibitors 1. Transforming growth factor beta: It inhibits growth in most cell types; however, it stimulates fibroblast and the production of collagen and fibronectin. 2. Alpha interferon. 3. Cell to Cell contact inhibition signals
  • 10. C) Extracellular matrix synthesis and Cell Matrix Interaction  The extracellular matrix (ECM) is a collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells
  • 11. ECM components Structural Proteins Adhesive glycoproteins Proteoglycans Functions of ECM It does much more than just fill the spaces around cells to maintain tissue structure.
  • 12. Regeneration Regeneration is proliferation of residual cells to replace the lost structures Regeneration involves  Cell proliferation, (driven by growth factors )  Integrated extracellular matrix, and  development of mature cells
  • 13. Repair by fibrosis  The main healing process is repair by deposition of collagen and other ECM components  SCAR.  In contrast to regeneration which involves the restitution of tissue components, repair is a fibro-proliferative response that “patches” rather than restores the tissue.
  • 14.
  • 15. Repair by fibrosis Stages: 1. Inflammation 2. Angiogenesis 3. Migration and proliferation of fibroblasts 4. Deposition of extracellular matrix 5. Organization of collagen “remodeling” 6. Fibrosis – scar formation.
  • 16. Angiogenesis Definition:  Angiogenesis is the process of new blood vessel formation, from a preexisting vessel.  VEGF is the most important growth factor involved in physiologic angiogenesis as well as angiogenesis occurring in chronic inflammation, wound healing and tumors.
  • 18. Granulation Tissue  Granulation tissue is the hallmark of tissue repair  Characters:- 1. Red granular 2. Soft, Moist 3. Bleeds easily
  • 19. Granulation Tissue  Microscopically: It is Formed of neo capillaries, extracellular matrix with fibroblasts +/- necrotic tissue and scattered inflammatory cells; macrophages.
  • 20. Repair of nervous system  No regeneration can occur.  The necrotic cells are removed by microglia and then replaced by proliferation of glial cells.  This process is called gliosis.
  • 21. Healing of wounds Healing by primary union (1st intention) Wound characteristics:  Non-gaping, clean (non infected), with minimal tissue loss and approximated edges. Examples:  Stitched surgical wound Healing by secondary union (2nd intention) Wound characteristics:  Gaping and infected wound with marked tissue loss and widely separated edges. Examples:  Abscess, ulcer, ……..
  • 22. Stages of wound healing 1. Clot formation 2. Granulation tissue 3. Epithelialization 4. Collagen Formation 5. Scar 6. Maturation of scar
  • 23.
  • 24. Healing by 2nd intention Healing by first intention Features Gaping wound Non-gaping wound Type of wound Present Usually not present Infection Larger amount Scanty The amount of granulation tissue Longer time Short Healing period The gap can’t be directly bridged Direct (bridge) healing Healing direction A prominent feature Generally not a feature Wound contraction Bigger and contracted scar Thin linear scar The outcome Frequent Infrequent Complications
  • 25. Factors That Influence Wound Healing Systemic Factors • Nutrition: e.g, vitamin C deficiency. • Metabolic status: DM is associated with delayed healing • Circulatory status • Hormones such as glucocorticoids have anti- inflammatory inhibit collagen synthesis. Local Factors • Infection • Mechanical factors, • Foreign bodies, • Size, location, and type of wound.
  • 26. Complications of wound healing 1. Cosmetic Deformities due to extensive scarring 2. Contracture : an exaggerated wound contraction 3. Function loss e.g. due to contracture of scars around joints. 4. Keloid: exuberant scar protruding on the surface.
  • 27. Complications of wound healing 5. Chronic Ulcer: loss of epithelial continuity. 6. Sinus: blind ended tract, opening to a surface by a single opening 7. Fistula(an opening tract between 2 hollow organs). 8. Implantation epidermoid cyst. 9. Rarely carcinoma.

Editor's Notes

  1. depending on the extent of injury and surrounding framework
  2.  Self-renewal is division with maintenance of the undifferentiated state
  3. because it results in persistent tissue injury and inflammation.