Tissue Engineering
Wound – disruption of body’s structure
Chronic wound – wound that fails to heal 3-4 months (chronic cutaneous ulcer)
Cutaneous ulcer – develops after another pathological lesion
Papule – elevation of skin with no fluid
Pustule – swelling of skin with pus
Natural Wound Healing Process
Inflammation (lag), tissue formation (proliferation) then tissue remodelling
phases
Inflammatory phase:
Lasts 4-6 days
1. Cytokines – PDGF, EGF, TNF, IGF and GM-CSF induce chemotaxis of WBCs plus
induces proliferation of fibroblasts, endothelial and epithelial cells
2. Vasoconstriction and haemostasis – rapid constriction of vessels, thrombocyte
aggregation, coagulation cascade and formation of clot made of matrix of fibrin,
fibronectin and thrombospondin
3. Fibrinolysis leaves newly formed granulation tissue
4. After clot formation vasodilation and increased permeability due to PGs and
histamine
5. Chemotactic GFs and phagocytosis – influx of WBCs, neutrophils and
transformation of monocytes
Tissue formation:
1. Angiogenesis and granulation tissue formation – GFs induce migration and
proliferation of endothelium plus capillaries invade fibrin matrix in wound. New
vasculature (granulation tissue) covers the wound and is made of collagen type
III with imbedded WBCs, fibroblasts and endothelial cells
2. Formation of ECM – fibroblasts produce collagen III, proteoglycans and
glycosaminoglycans restoring integrity of granulation tissue and ECM. Collagen
produced by hydroxylation of Pro and Lys requiring co-factors O, Fe and vitamin
3. Re-epithelialisation – migration, proliferation burst and differentiation of
keratinocytes as they detach from basal lamina. Lamellopodial crawling
reinserting actinomyosin filaments
4. Wound contraction – modified fibroblasts activated by TGF-B1 produces
myofibroblasts that have actin like movements. NO acts on endothelial cells,
keratinocytes and fibroblasts affecting collagen deposition
Tissue remodelling:
1. Can take up to 2 years as dynamic equilibrium between synthesis of new
collagen and degradation of old
2. Collagen type III replaced by stable type I that align forming scar tissue
Chronic wounds:
Increased enzymatic activity of matrix proteases – increased MMP activity and
decreased MMP inhibitor (TIMPs) activity allows degradation of GFs and
connective tissue
Reduced response to GFs – GFs are degraded by MMPs and reduced GF-R
expression
Cell senescence – cells grow old due to continuous stimulation to proliferate
Wound – disruption of body’s structure
Chronic wound – wound that fails to heal 3-4 months (chronic cutaneous ulcer)
Cutaneous ulcer – develops after another pathological lesion
Papule – elevation of skin with no fluid
Pustule – swelling of skin with pus
Natural Wound Healing Process
Inflammation (lag), tissue formation (proliferation) then tissue remodelling
phases
Inflammatory phase:
Lasts 4-6 days
1. Cytokines – PDGF, EGF, TNF, IGF and GM-CSF induce chemotaxis of WBCs plus
induces proliferation of fibroblasts, endothelial and epithelial cells
2. Vasoconstriction and haemostasis – rapid constriction of vessels, thrombocyte
aggregation, coagulation cascade and formation of clot made of matrix of fibrin,
fibronectin and thrombospondin
3. Fibrinolysis leaves newly formed granulation tissue
4. After clot formation vasodilation and increased permeability due to PGs and
histamine
5. Chemotactic GFs and phagocytosis – influx of WBCs, neutrophils and
transformation of monocytes
Tissue formation:
1. Angiogenesis and granulation tissue formation – GFs induce migration and
proliferation of endothelium plus capillaries invade fibrin matrix in wound. New
vasculature (granulation tissue) covers the wound and is made of collagen type
III with imbedded WBCs, fibroblasts and endothelial cells
2. Formation of ECM – fibroblasts produce collagen III, proteoglycans and
glycosaminoglycans restoring integrity of granulation tissue and ECM. Collagen
produced by hydroxylation of Pro and Lys requiring co-factors O, Fe and vitamin
3. Re-epithelialisation – migration, proliferation burst and differentiation of
keratinocytes as they detach from basal lamina. Lamellopodial crawling
reinserting actinomyosin filaments
4. Wound contraction – modified fibroblasts activated by TGF-B1 produces
myofibroblasts that have actin like movements. NO acts on endothelial cells,
keratinocytes and fibroblasts affecting collagen deposition
Tissue remodelling:
1. Can take up to 2 years as dynamic equilibrium between synthesis of new
collagen and degradation of old
2. Collagen type III replaced by stable type I that align forming scar tissue
Chronic wounds:
Increased enzymatic activity of matrix proteases – increased MMP activity and
decreased MMP inhibitor (TIMPs) activity allows degradation of GFs and
connective tissue
Reduced response to GFs – GFs are degraded by MMPs and reduced GF-R
expression
Cell senescence – cells grow old due to continuous stimulation to proliferate
