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

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Bone tissue engineering

 The companies involved in the bone regeneration are usually not only focusing on this.

Tissue Engineering Requirement for bone graft

  1. Tumour (leaves big hole e.g. maxiliofacial)

  2. Total joint arthroplasty (bone stock, particularly poor in revision surgery)

  3. Trauma reconstruction (large bony and soft tissue defects)
    Bad fractures, loose bone fragments at the site.

  4. Arthrodesis (normal bone but want more for fusion e.g. spine, see above)
    also for joints when they are not any more intensively used but do hurt.

Scaffold Considerations

  • Appropriate for cell attachment and proliferation

  • Delivery of bioactive molecules

  • Mechanical properties comparable to bone

  • Porous with controlled degradation

  • Sterilisable
     appropriate techniques!

  • Injectable, mouldable and processable ???

  • Available when needed
     fractures are random…

3rd Generation scaffolds

  • Matrix-Based (degradable scaffolds)

  • Cell-Based (Mesenchymal cells implants onto scaffolds or delivered by it)

  • Bone Morphogenetic Protein-Based (delivery by degradable polymers)

  • In vitro studies: already cellular attachments after 1 day, significant proliferation: 14 days.

  • In vivo studies on rabbits by inserting a piece of matrix in the ulnar: you want to see the different effects in the defect. The easiest way to evaluate bone healing is with x-rays.
    The integration of the matrix is most critical in the middle (studying with histology), collagen fibers with mineral are produced by integrated cells.
    Ulnar effect:
    4 groups are tested; matrix alone, matrix with marrow, matrix with OP1, matrix with OP1 and marrow. (OP1 is of the BMP-family (BMP3)).
    Conclusion: OP1 with or without marrow is not much difference, so probably marrow is the least important and matrix most.

  1. Osteogenic (stem or precussor cells)

  2. Osteoconductive (synthetic biomaterial bone graft)

  3. Osteoinductive (autocrine, paracrine or added growth factors (BMP’s))

  • Osteoinductive materials: the use of hydroxyapoptite, DCP and TCP (calciumphosphate). A porous material, processed at high temperatures (ceramics). The temperatures do influence the way the wound heals.

The effect of processing temperature on microporosity; at higher temperatures the pore size is bigger. Also the chemical aspects of the material change.
Test: 1100ºC: 35% mature bone, 1200ºC: 15% mature bone, 1300ºC: 0% mature bone
So a lower temperature for sintering production of the scaffold is important.

College 3 – “Articular cartilage” – 9th of January 2012

Articular Cartilage

Covers the bone in synovial joints (it is a bearing surface, there is a lubricant (synovial fluid) for very low friction very little wear).


  • Protect bone from high stresses  cartilage reduces the stresses

  • Low friction, low wear bearing surface

  • Slow remodelling (‘Cartilage once destroyed, is not repaired’)
    avascular, aneural, alymphatic, so no normal healing mechanism.
     Cartilage gets the nutrients from movement of synovial fluid (“like a sponge”)
     Oxygen gradient (at top 7%, bottom 1-2%)
     Chondrocytes are preferentially glycolytic (instead of oxygen), so low enery/metabolic cells.

Clinical Problem


  • Meniscal cartilage is from fibrous cartilage (only in jaw and knee  knee rolls)

  • When there is damage on the meniscal cartilage, the knee locks.

  • It has load bearing properties.


  • Chondrocytes (cartilage cells, 10% vol.)
    * The cells shape change: I ellipse, II/III rounded/spherical, IV rounded(columns) depends on ECM
    The density of proteoglycans rises when you get deeper, the collagen density decreases.

  • Extracellular matrix

    • Collagen

    • Proteoglycan (chrondroiten sulphate, keratin sulphate, hyaluronan (wants to swell l(absorb water) collagen does not)

  • Water (70%-80%)

  • Non-collagenous proteins

Cartilage defects

  • Causes are sporting, work-related injuries and road traffic accidents

  • A lot of people get cartilage problems at an older ager because of cartilage damage.

  • 2 types of cartilage defect:

  • Mechanical loading:
    Cartilage is loaded cyclically (106 cycles per year), moreover the loading level can be quite significant (it can be 20% of the stress level).

  • Therapy:

    • Pharmacology  “all drugs that work will have side effects”

    • Microfractures drill down into subchondral bone and release cells (only repair with growth factors)

    • Tissue graft

    • Use fibrocartilage as repair tissue

    • Cell transplantation

       You inject back some autologous cells, you sow on a patch (biomaterials or periosteum (they were hoping that some stem cells of the periosteum helped the healing)).
       In 2D culture chondrocyte dedifferentiate into fibrochondrocytes  you can see the change from ECM (chondrocyte produce collagen type 2 and fibrochondrocytes collegen type 1).
       Chondrocytes have a strain history, so less loaded chondrocytes differ from more loaded ones.
       Although there is a patch, they still lose some cells.
      Success is questionable, since it will only help for 10 years.

Tissue Engineering

  • Mechanical loading
    Extracellular events: pH and osmatic pressure change (swelling), hydrostatic pressure,
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