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.
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.
Osteogenic (stem or precussor cells)
Osteoconductive (synthetic biomaterial bone graft)
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
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
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.
Current repair - poor long term success (quite reasonable on short term).
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.
Proteoglycan (chrondroiten sulphate, keratin sulphate, hyaluronan (wants to swell l(absorb water) collagen does not)
A lot of people get cartilage problems at an older ager because of cartilage damage.
2 types of cartilage defect:
Cartilage is loaded cyclically (106 cycles per year), moreover the loading level can be quite significant (it can be 20% of the stress level).
Pharmacology “all drugs that work will have side effects”
Microfractures drill down into subchondral bone and release cells (only repair with growth factors)
Use fibrocartilage as repair tissue
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.