REPAIR TISSUE REPAIR

7/3/2012 1 TISSUE REPAIR REPAIR Maintenance of normal structure and function and survival of the organism Regeneration Healing: scar formation and fib...

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7/3/2012

REPAIR

TISSUE REPAIR



Regeneration : growth of cells and tissue to replace lost structure  

Tissue with high proliferative activity : hematopoietic tissue, epithelium Intact connective scaffold



Maintenance of normal structure and function and survival of the organism



Regeneration



Healing: scar formation and fibrosis

Factors involving tissue repair   



Healing : restore original structures involving collagen deposition and scar formation 



Tissue proliferative activity Stem cells Growth factors and chemical mediators Extracellular matrix

Wound, inflammation, necrosis

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REGENERATION 

Regenerative capacity attributed to two main factors  





Post hepatectomy : secretion of cytokine and growth factors 

Secretion of TNF, IL-6  G0  G1 TNF Activation of metalloproteinase



Metalloproteinase  Secretion of HGF, TGF-



The capacity of cell to reenter the cell cycle Efficient differentiation of stem cells in area of injury

Regeneration : Bone marrow, epithelium

 



Liver regeneration 

Compensatory hypertrophy and hyperplasia



HGF, TGF-  G1  S Norepinephrine, Insulin, Thyroid hormone

TGF-, Activin

HEALING, SCAR FORMATION AND FIBROSIS  

 Severe

tissue injury  Chronic injury  Damage of parenchymal cells and stromal framework of the tissue

  



Inflammation Angiogenesis Migration and proliferation of fibroblasts Scar formation Connective tissue remodeling Hallmark of healing : proliferation of fibroblasts and endothelial cell to form granulation tissue

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ANGIOGENESIS 

Angiogenesis





Neovascularization





Endothelial precursor cells (EPCs) : vascular implants, ischemia





Pre-existing vessels

 

Vasodilation (NO) and increased vascular permeability (VEGF) Degradation of basement membrane (metalloproteinase) and disruption of cell to cell contact (PA) Migration and proliferation of endothelial cells Maturation Recruitment of periendothelial cells

CUTANEOUS WOUND HEALING 

Growth factors in angiogenesis 

Growth of endothelial cells  Vascular endothelial growth factor (VEGF) 

Inducing agents of VEGF : Hypoxia, TGF-, PDGF, TGF-

Fibroblast growth factor (FGF) Recruitment of pericytes and smooth muscle cells  Angiopoietin  Platelet-derived growth factor (PDGF) Synthesis of extracellular matrix  Transforming growth factor-  (TGF-)

 



 

Inflammatory process Granulation formation and re-epithelialization Extracellular matrix deposition, wound contracture and tissue remodeling First intention wound Second intention wound

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HEALING BY FIRST INTENTION 

24 hr : migration of neutrophils, reepithelialization



Day 3 : migration of macrophages, granulation tissue formation, collagen synthesis



Day 5 : more granulation tissue formation and collagen synthesis, bridge in the incision, epidermis recover normal thickness



Week 2 : continue proliferation of fibroblasts and collagen deposition



1 month : complete scar formation

Growth factors and cytokines affecting in wound healing 

Monocyte chemotaxis



Fibroblast migration/replication Keratinocyte replication Angiogenesis

   

Collagen synthesis Collagenase secretion

     

Chemokines, TNF, PDGF, FGF, TGF-β PDGF, EGF, FGF, TGF-β, TNF, IL-1 HB-EGF, FGF-7, HGF VEGF, angiopoietins, FGF TGF-β, PDGF PDGF, FGF, TNF; TGF-β inhibits

HEALING OF SECOND INTENTION  More inflammatory process  More granulation tissue formation  More wound contracture : myofibroblasts  Thinning of new epithelium WOUND STRENGTH  1 week : 10%  3 months : 70-80%

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FACTORS THAT INFLUENCE WOUND HEALING  Local

factors

Infection  Physical factors  Foreign body  Type of tissue 



Systemic factors  Nutritional factors : protein, vitamin C  Metabolic status : DM  Blood circulation  Hormonal status

COMPLICATION IN CUTANEOUS WOUND HEALING  Inadequate formation of granulation tissue and scar formation  Excessive formation of the repair components    



Hypertrophic scar Keloid Exuberant granulation Aggressive fibromatosis

Formation of contracture

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