ebme 306 lectures 3-5 fall-2015-ziatsc (5).ppt
TRANSCRIPT
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Biological Constraints in Using Biomaterials- Inflammation Readings for September 2, 4 & 9:
Biomaterials: The Intersection of Biology and Materials Science, J.S. Temenoff and A.G. Mikos, Pearson/Prentice Hall, 2008, pp. 327-335, 369-384, 385-393
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BIOMATERIALS-TISSUE INTERACTIONSHemostasis/Thrombosis
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Acute InflammationChronic InflammationHealing, FibrosisGranulation Tissue, GranulomasCell Injury and NecrosisSEQUENCE of EVENTS of BIOMATERIAL RESPONSESSurgery, Material Implanted
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CAUSES of CELL INJURYMaterials (biomaterials)SurgeryHypoxiaPhysical AgentsChemicals and DrugsMicrobiologic AgentsImmunologic ReactionsGenetic DefectsNutritional Imbalances
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CELL/TISSUE INJURY CELL INJURYreversible vs. irreversiblepoint of no return
CELL DEATHNecrosis- the summation of the morphologic changes following cell death in living tissueApoptosis- programmed cell death
ADAPTATION- cells responses to stress
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Materials & Biomaterials
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CELL INJURY CAUSES NECROSISNormal Heart Tissue
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CELLS ADAPT to INJURY/STRESS
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REGENERATIVE CAPACITY of CELLS The growth response depends on the cell type:
LabileStable Permanent
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ATROPHY
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HYPERTROPHYWheres the beef?
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HYPERTROPHYCor bovinum
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Hyperplasia (Fibrosis around Biomaterials) Fibroblast Proliferation Increased ECM (collagen)+Fibrosis
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HYPERPLASIAFIBROSIS & FIBROUS ENCAPSULATIONPolymerCellsCollagen and other ECMs
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Acute InflammationChronic InflammationHealingGranulation tissueCell Injury and NecrosisSEQUENCE of EVENTS of BIOMATERIAL RESPONSE to INJURYSurgery, Material Implanted
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INFLAMMATION, HEALING & BIOMATERIALSLocal reaction of vascular (or vascularized) tissue to injuryOccurs in both acute and chronic inflammation!!
TWO MAIN THEMES:Destruction of tissue- or walling off of biomaterial Repair- by normal parenchyma or by scar (fibrosis)
TEMPORAL PATTERNACUTE- short duration, exudative- cells + proteins, PMNsCHRONIC- long duration, macrophages/lymphocytes, proliferative cells-fibroblasts and blood vessels
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CELLS of INFLAMMATION
Erythrocytic Granulocytic MononuclearMegakaryocyticBone Marrow stem cells + Growth factorsWhite Blood cellsPlateletsPMNs=neutrophils Eosinophils BasophilsMonocytes T & B Lymphocytes
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WHERE DO THESE CELLS COME FROM?
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Bone MarrowBoneFat
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EosPMN-segBasoMonoLymphoPlateletPMN-band
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INFLAMMATION and BIOMATERIALSSequence of EventsInjuryAcute inflammationChronic inflammationGranulation tissueForeign body reactionFibrosis
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ACUTE INFLAMMATIONShort duration
Hours to a few days
Hemodynamics, Vascular permeability, Leukocyte migration
Exudative or exudatesAre protein and cells which bind to biomaterials, pus is an exudate
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CalorRuborTumorDolor
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HEMODYNAMICS and INFLAMMATIONQ or Jv = ([Pc Pi] [c i])
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Q or Jv = ([Pc Pi] [c i]) Pc-Pic i
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TRANSUDATES vs. EXUDATES
CHARACTERISTICTRANSUDATEEXUDATEDefinition & EtiologyHemodynamic, an ultrafiltrate of plasmaInflammatoryInflammatory cellsNoneYesBacteriaNoneOftenProteinLow (4%)Specific Gravity1.020ExamplesCongestive heart failure, blisterPneumonia, abscesses, pus
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TRANSUDATEThis is a right pleural effusion (in a baby). Note the clear, pale yellow appearance of the fluid. This is a serous effusion. Fluid appears grossly clear.
Effusions into body cavities can be further described as follows: Pleural effusionsAscitesPericardial effusion
from Webpath 7.0
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EXUDATEPUS!!!!
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LEUKOCYTES in INFLAMMATIONAlso known as White Blood Cells (WBCs)Granulocytes- PMNs, Eosinophils, BasophilsMonocytesLymphocytes
Mast cells- are tissue cells, not in circulating blood
Normal value (blood) is 10,000 cells/cubic mmLeukocytosis (or philia)- >10,800/cubic mm, increased numbersLeukopenia-
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INFLAMMATION & BIOMATERIALSHEALINGCell & Tissue Response
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Leukocytes in InflammationAcuteChronic
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PMNsMononuclearcellS
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Other Cells/Components of Inflammation
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LEUKOCYTES in INFLAMMATIONfrom Webpath 7.0Capillary(Blood) SideMaterial with Bacteria
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Leukocytes in InflammationPhagocytosisClick on the link above, need to be in full slide mode
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Chemical Mediators of Inflammation
Plasma-derived Circulating precursors Have to be activated
Cell-derivedsequestered intracellularly synthesized de novo
Most mediators bind to receptors on cell surfaces but some have direct enzymatic or toxic activity
Mediators are tightly regulated
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INFLAMMATION-MEDIATORS
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ARACHIDONIC ACID PATHWAY
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COMPLEMENT SYSTEMand biomaterial surfacesComplement binds to biomaterials and is activated by biomaterialsBiomaterials
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FEVER, IL-6
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Acute InflammationChronic InflammationHealing, FibrosisGranulation Tissue, GranulomasCell Injury and NecrosisSEQUENCE of EVENTS of BIOMATERIAL RESPONSE to INJURYSurgery, Material Implanted
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CHRONIC INFLAMMATION
Long duration
Few days, weeks, months
Proliferative- fibroblasts and blood vessel divideBut also- macrophages & lymphocytesNote- macrophages do not divide
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Leukocytes in InflammationAcuteChronic
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MACROPHAGES and FBGCs(Biomaterials)
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MACROPHAGES, FBCGs and BIOMATERIALS
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Foreign Body Giant CellsSuture
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IN VIVO BIOCOMPATIBILITY TESTINGCage Implant SystemMaterialCageImplantationDays 7, 14 and 21Exudates Analyzed for Cell CountsSurfaces Explanted and Adherent Cells Analyzed
Insertsyringe
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MACROPHAGES and FOREIGN BODY GIANT CELLSFusion
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MACROPHAGES and BIOMATERIALSThe Big Mac Attack--- DegradationBIOMATERIAL DEGRADATION-OHH202-O2Enzymes+HPits, holes etc.
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FREE RADICALS
FREE RADICALS- any atom or molecule with an unpaired electron in its outer orbit, that can exist independently for a period of time
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Reactive Oxygen Species, Free Radicals & AntioxidantsAntioxidants
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PACEMAKER LEAD DEGRADATIONMacrophage adhesionForeign body giant cells (FBGC)Surface pittingSurface crackingFull thickness crackingDEVICE FAILUREExplanted pacemaker leadAdherent macrophages & FBGC release degradative enzymes and radicals.
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FBGC - Mediated Surface Degradation
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ACUTE INFLAMMATION & ROS
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Acute InflammationChronic InflammationHealingGranulation Tissue, GranulomasCell Injury and NecrosisSEQUENCE of EVENTS of BIOMATERIAL RESPONSE to INJURYSurgery, Material Implanted
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INFLAMMATION & BIOMATERIALSHEALINGCell & Tissue Response
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GRANULATION TISSUEA complex of macromolecules and cells, macrophages, blood vessels, fibroblasts
Blood vessels formation is referred to as neovascularization or angiogenesis
Biomolecules are produced by cells that results in a soft, watery, connective tissueGlycosaminoglycans (GAGS)Glycoproteins- fibronectin, lamininCollagens
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HEALING RESPONSE to BIOMATERIALSBiomaterialFibrosis:Collagen-richGranulation Tissue:GAG-richInfection following Implantation
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GRANULATION TISSUEGAGSBlood Vessels
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ANGIOGENESIS in GRANULATION TISSUE
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TISSUE RESPONSE to BIOMATERIALSGRANULATION TISSUE-H&EGranulation tissue:Blood vesselsGAGsSome MacsSome fibroblasts
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GLYCOSAMINOGLYCANSHighly Sulfated-binds to water
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GLYCOSAMINOGLYCANS
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Acute InflammationChronic InflammationHealing, FibrosisGranulation TissueCell Injury and NecrosisSEQUENCE of EVENTS of BIOMATERIAL RESPONSESSurgery, Material Implanted
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INFLAMMATION & BIOMATERIALSHEALINGCell & Tissue Response
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HEALING RESPONSE to BIOMATERIALSBiomaterialFibrosisGranulation Tissue
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FIBROUS TISSUEor Scar TissueA complex of macromolecules and cells, macrophages, blood vessels, fibroblasts
Biomolecules are produced by cells that results in a hard, tough, connective tissueGlycoproteins- fibronectin, lamininElastinCollagens- type III than type I, type I collagen makes up the final scar tissue
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FIBROSIS & FIBROUS ENCAPSULATIONPolymerCellsCollagen and other ECMs
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EXTRACELLULAR MATRIX- COLLAGENType III collagen is produced first thancells (fibroblasts) produce Type I collagen
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7 days14 days21 days28 daysFIBROUS ENCAPSULATION
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GROWTH FACTOR FAMILIES
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GROWTH FACTORSCELLCell responses:growth, migration, shape etc.
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FIBROBLAST RESPONSES Growth Factors and Cytokines FIBROBLAST RESPONSES
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CYTOKINES and LYMPHOKINESImportant in Biomaterials ApplicationsCYTOKINES- from cells, Cell derived products- Soluble or membrane bound INTERLEUKINS- 1-37Key Interleukins for Biomaterials (IL-1, IL-4, IL-6, IL-13)
TUMOR NECROSIS FACTOR- TNF-a
COLONY STIMULATING FACTORS- GM-CSF
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Cytokines and Lymphokines
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SUMMARY of the INFLAMMATORY RESPONSE to BIOMATERIALSHEALINGCell & Tissue Response
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SUMMARYCellular Injury and adaptations Acute vs. chronic inflammation- fluids, cells, timeTransudates vs. exudatesMacrophages and Foreign body giant cell response to biomaterialsFree radicals and material degradationGranulation tissue vs. scar (fibrous encapsulation) tissueFibroblast responses and healing phase- cell types, growth factors, cytokines
Resize of Shoulder_abscess_liquefactive_necrosis_gross.JPGREMEMBER THIS DIAGRAM
Granulation tissue fibrotic tissue
What cell types make proteoglycans? FibroblastsWhat about Collagen? Osteofibroblasts
How do they do this? How many collagens in human body? 28Chains in type 3 is lose, whereas type 1 is very distinct (every 64 nm), providing strong tensile tissue reticular collagenWhy is the thickness decreasing? Inflammation is decreasing, less collagen, cells are contracting down, less proliferate Molecular weights : 20,000 kDa
Except peptidesBind to growth factor receptor, then signal transduction, activation of pathway, and cell responses occurRemember whatever is in red