Biomedical Engineering Reference
In-Depth Information
intelligent instructive scaffolds is also being increasingly explored,
as discussed elsewhere. This can incorporate growth factors to
inducevesselinvasionorperhapsgenevectorstoupregulateexpres-
sion of VEGF, for example, thereby expediting vessel invasion fol-
lowing implantation. This type of research is at the cutting edge
of current scientific approaches to bone and cartilage repair. Pre-
conditioning MSCs to hypoxia prior to implantation is also being
explored.
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Thereis,however,perhapsamuchmorelogicalapproachtoform
bone.Whynotinduceboneformationbyendochondralossification?
In this scenario a construct of chondrogenically primed MSCs or
perhaps even a MSC-derived cartilage template would be implanted
and allowed to progress further along the endochondral ossifica-
tion route to form bone naturally. This approach has several advan-
tages. First, MSCs are known to progress along the endochondral
ossification route, naturally becoming hypertrophic, as occurs very
oftenincartilagetissueengineeringapproaches.
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Second,chon-
drocytes usually reside in an environment of very low oxygen ten-
sion. Placing an unvascularized cartilage-like template into such an
environmentshould notresult incelldeath, aswouldnormallyhap-
pen. Third, as explained earlier, endochondral ossification is char-
acterized by attraction of vessels by the hypertrophic chondrocytes,
whichoccurssimultaneouslywithboneformation.Thisistheoppo-
site of the intramembranous approach usually used in tissue engi-
neering, whereby bone formation is stimulated by an increase in
vessel density, which has already occurred. A combination of this
approachwithnewscaffoldscouldofferhugepotentialforthefields
of both bone and osteochondral tissue engineering. Of course the
challenge will be to maintain the chondral layer in an unhyper-
trophic, unvascularized state. However, with new instructive scaf-
folds and the surrounding cartilaginous and synovial environment,
perhaps this will occur naturally. This approach is looking increas-
ingly promising with recent research demonstrating the stability
of implanted MSCs in chondral defects.
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In vitro
these same cells
produced collagen type X and became hypertrophic; however, when
implanted directly without
in vitro
culture, the same cells showed
much lower expression of collagen type X and degrading enzymes
indicative of the endochondral ossification process. Generation of
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