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Mechanical Forces & GF (1) (GF (Bone (Bone Formation Cellular Events,…

- - - - Applied Physical Force => Secondary Force
        
        Bone
        
        Bone Deformation => Bone Cells Deformed => Pressure Gradients/Interstitial Fluid Flow => Applies Shear Stress to osteoblasts & osteocytes
    - - Primary/Secondary Physical Stimulus => Electrical, Chemical/Biochemical response
      - Mechanotransducers
        
        Mechanically Activated Ion Channels (MAC)
        
        Receptors
        
        G Proteins
        
        Cytoskeleton
      - Pharmacological Inhibitors
        
        Control tissue development
      - Pharmacological Stimulators
        
        Control tissue development
    - - Biochemical Signal Conversion
      - Signal Transduction Pathways
        
        Stimulated by physical forces
        
        Same as biochemical agonists + initial biochemical event (G Protein Activation) is mechanically induced
        
        G Protein Activated => Resultant downstream biochemical events same
    - - Initial Stimulus => Final Tissue-Level Response
      - Signal Transduction Pathways Activation
        
        Regulate cellular activities
        
        Gene Expression
        
        Protein Synthesis
        
        Autocrine Release
        
        Paracrine Release
  - - - GF
      - Hormones
      - Steroids
- - - - Strain & Stress
        
        Bone
        
        Cartilage
    - - Compression
        
        Bone
        
        Cartilage
  - - - Endothelium
    - - Endothelium & Vessel Wall
  - - - Bone
    - - Skin
  - - - Tissue Remodeling
- - - - Bearing Surfaces
        
        Load -Bearing
        
        Thicker
        
        Stronger
        
        High Glycosaminoglycan (GAG) Conc
        
        Decrease if joint immobilised
        
        Restore if joint remobilised
        
        GAG Synthesis
        
        ~ High Velocity
        
        Mechanical Stimulation
        
        1 more item...
        
        x~ Pressure
        
        Non Load-Bearing
      - Response to mechanical loading in vivo/in vitro
        
        Increase ECM production
        
        Stronger tissue
  - - - Stationary Cultures
      - Small MF systems
        
        Spinner Flask
        
        Petri Dish
        
        Rotating Bioreactor
  - - - Enhance Quality
        
        Modify mechanical enviro
        
        Better
        
        Improve biochemical and mechanical properties
        
        Small-Amplitude Cyclic Compression Devices
- - - - Mechanical Loading
        
        Low
        
        Bone Mass loss
        
        in vivo
        
        In vitro
    - - Areas exposed to stress
        
        Increase Strength & Density
      - Areas not exposed
        
        Opp
  - - - Tissue Development
- - - - Fluctuating Blood Pressure by cardiac cycle
        
        Cyclic Strain
        
        Endothelium
        
        Vascular Smooth Muscle Cells
      - Blood Flow
        
        Shear Stress
        
        Endothelium
      - Result
        
        Regulate endothelial functions
        
        Vasoregulation
        
        Transversal Transport
        
        Thrombogenesis Inhibition
    - - Endothelial Cells
        
        Nonthrombogenic surface
      - Smooth Vascular Muscle Cells
        
        Phenotypes
        
        Contractile
        
        Vessel Wall Strength & Contraction
        
        YES!
        
        Successful Bioartificial Artery
        
        Culture smooth muscle cells impt!
        
        Secretory
        
        Hyperplasia & Vessel Occlusion
        
        Transformation
        
        Contractile => Secretory
        
        Smooth muscle cells harvested from native vessels and cultured in vitro
  - - - Limit Usage
    - - Seed vessel with endothelial cells before surgical implantation
        
        Problem: Detachment of cells from prosthesis upon fluid flow exposure
        
        Solution: Precondition them to flow for cell retention
        
        Pretreated Grafts
        
        Less thrombogenic than static grafts
        
        Improve in vivo performance
    - - Develop Bioartificial Blood Vessel
        
        Resemble native vessel
        
        Improve Patency ("Openness")
        
        Needs reinforcement
- - - - Gene Expression
      - DNA Synthesis
  - - - In vitro control of growing tissues
    - - In vivo
        
        Aid tissue regrowth/regeneration
      - Implant alone/another
  - - - Preserve healthy cartilage
      - Growth & Metabolism
    - - Insulin-Like GF-1
        
        Stimulates mitotic activity
        
        Inhibits chondrocyte-mediated matrix catabolism
        
        Preserve mechanical function of cartilage
      - Basic Fibroblast GF
        
        Potent Mitogen
        
        Promote anabolic & catabolic matrix processes
        
        Promote cartilage repair in vivo
      - Transforming GF-beta
        
        Stimulate & Inhibit proteoglycan synthesis
        
        Biodegradable Polymer Scaffolds + TGF-beta1
      - Platelet-derived GF
        
        Stimulate proteoglycan synthesis in articular cartilage explants
      - Bone Morphogenetic Protein-2B
        
        Stimulate proteoglycan synthesis in articular cartilage explants
  - - - Chemotaxis of osteoblasts precursors
      - Increase of committed osteoblast precursors
      - ECM Maturation
      - Mineralization
    - - Regulate
        
        Systemic Hormones
        
        Local Mechanical Stress
  - - - Smooth Muscle Cell
        
        bFGF
        
        PDGF
        
        Heparin-Binding EGF-like GF
        
        Betacellulin
        
        Endothelia-1 (ET-1)
      - Endothelial Cell
        
        bFGF
        
        VEGF