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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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