College 1 – “An introduction to Tissue Engineering” – 22nd of November 2012

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cell deformation, fluid flow, electrical streaming potentials (ions)
Intracellular events: nucleus distortion, mechano ion channels, integrins, mitochondria distortion, cytoskeletal reorganisation, nitric oxide, Ca2+ signalling (downstream mechanical responses), nucleotide release.
Agarose gels

  • Isolated chondrocytes are put in the agarose
     similar sugar composition as proteoglycans

  • More simple transfer function than normal cartilage  simplification model system  easier to see what is happening.
    (too much squeezing  cell ruptures)

  • Phenotype is retained (when the ECM is digested the cell becomes round again.

  • Reproducible and well established system and enable examination of the effects of the cell deformation on signalling pathways.

  • Bovine cells:

    • Max. strain of 15% (representable level)

    • Cell proliferation of dynamic tests do up regulate (static down), is dominated by superficial cells (higher density of cells on top).

    • GAG production only regulates up at 1 Hz (static down), is dominated by deep cells (higher density of GAGs). Optimisation of 15% strain always on 1 Hz (humans, horses).

 So we need both the layers!

 Dynamic compression inhibits the synthesis of NO (NO= bad  reduction of cell proliferation and production of GAGs). Cells that produce interleukin-1β (stimulates inflammation), an inhibitor of NO reverses this effect.

 Everyone should load mechanically (also old people!).

    • Human chondrocytes need a growth factor (TGFβ) before they will be active and so no effect in the culture media.
       Lots of interplay between mechanical loading and biochemical responses, integrin blocking will result in no responses to mechanical loading.

  • Scaffold materials
    Explants, agarose, fibrin, PEGDM, PLA/PCL
    Most of the scaffold look okay, but the mechanical properties are not good (compressive stiffness modulus of cartilage 1-10MPa, agarose 100kPa).

  • Bioreactor
    In Vitro (in a bioreactor  a controlled environment)
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