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Bleed First Harvest Later. Arjan van den Hil European Sales Manager Leipzig, Dezember 18, 2006. Blood. „Blut ist ein ganz besonderer Saft!" Mephisto in Faust Goethe 1808 Früher wurde das Blut als Sitz der Seele und des Lebens angesehen. Blood Components.
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Bleed FirstHarvest Later Arjan van den Hil European Sales Manager Leipzig, Dezember 18, 2006
Blood „Blut ist ein ganz besonderer Saft!" Mephisto in Faust Goethe 1808 Früher wurde das Blut als Sitz der Seele und des Lebens angesehen.
Blood Components • Human blood consists of 22% solids and 78% water. Its different components are plasma (with all the different blood cells), fat globules, chemical substances (proteins, carbohydrates, hormones, etc.) and gases (oxygen, nitrogen, carbondioxide, etc.)
thrombopoietin Platelets platelet count circulation Destruction/removal (spleen, liver) Production (bone marrow) 70% spleen 30%
The Healing Process: The Role of Platelets When an injury occurs, platelets attach to the connecting tissue. The platelets form a loose plug and are activated by thrombin. Thrombin converts fibrinogen into fibrin.
The Healing Process: The Role of Platelets A fibrin matrix is formed, which finally results in a blood clot. Platelets are releasing growth factors and cytokines
Platelet Functions • Haemostasis • Primary haemostasis • Secundary haemostasis (coagulation) • Inflammation • Antimicrobial host defence • Wound and/or bone healing, through the release of growth factors and other mediators
Activation of Platelets: Release of Growth Factors and Cytokines + Thrombin activation Platelets in rest Platelets activated
Activation of Platelets: Release of Growth Factors and Cytokines
Growth Factors and Cytokines in Platelets and White Blood Cells • Connective-tissue activating peptide III • Lipoxygenases • Antiplasmin • Histamine • EPEA • LMW-EMA • HMA-EMA • 12-HETE, 15-HETE • PGE1, PGE2, PGA2, PGJ2, PGF1a, PGF2a • Serotonin • ADP • PDGF-AA,BB, AB • TGF-1, 2 • VEGF • EGF • bFGF • IGF-I • PD-ECGF • HGF • Osteocalcin • Fibronectin • Fibrinogen • Platelet Factor 4 • P-Selectin • Ca2+
PDGF VEGF FGF Growth Factor Effects: Angiogenesis
IGF TGF- PDGF Growth Factor Effects: Chemotaxis
EGF PDGF TGF-b Growth Factor Effects: Mitogenesis
TGF- Growth Factor Effects: Differentiation
Role of Growth Factors • PDGF • Stimulates cell replication • Promotes angiogenesis • Promotes epithelialisation • Promotes granulation tissue formation • TGF • Promotes formation of extracellulair matrix • Regulates bone cell metabolism • VEGF • Promotes angiogenesis • EGF • Promotes cell differentiation • Stimulates re-epithelialisation, angiogenesis and collagenase activity • FGF • Stimulation of angiogenesis • Promotes proliferation of endothelial cells and fibroblasts
Role of Inflammatory mediators • Serotonin • Vasoconstriction, increased capillary permeability • PDGF • Chemotaxis, vasoconstriction, SMC proliferion, activation of monocytes and neutrophils • -TG • Neurophil recruitment • TGF- • Chemotaxis, inhibits neutrophil apoptosis, fibroblast proliferation
Role of Antimicrobial Proteins in Host Defence • Toxic O2 metabolites (e.g. O2-, H2O2, OH-) • All are potent antimicrobial activity • Antimicrobial peptides (e.g. PF4, PBP, CTAP-3, NAP-2, RANTES, TB-4, FPA, FPB) • Chemotactic receptors (e.g. C3a, CCR, C5a, thrombocidins) • Involved in guiding platelets towards sites of microbial infection • Platelets are the first cells to arrive at a site of infection!
Synergistic Action of Growth Factors • Vascularisation: VEGF and bFGF • Asahara et al. Circulation. 92:365. 1995. • Migration: PDGF and TGF- • Lind M. Acta Orthop. Scand. Supp. 283:2. 1998. • Proliferation: PDGF, TGF-, and EGF • Slater et al. J. Orthop. Res. 13(5):655. 1995. • Differentiation: FGF, TGF-, and IGF • Kasperk et al. Growth Factors. 3:147. 1990.
Wound Healing & Bone Regeneration: Role of Platelets Platelet Degranulation