Biomedical Engineering Reference
In-Depth Information
injury differentiate along the osteoblastic lineage and, eventually, produce
both compact and trabecular bone in the absence of cartilage production.
after 72 hours, osteoblasts from the cortex and committed osteoprogenitor
cells from the periosteum proliferate and differentiate to form immature
bone. Endochondral bone formation involves the recruitment, proliferation
and differentiation of undifferentiated mesenchymal cells into cartilage. MSC
proliferation can be detected as early as three days after fracture and is high
for several days 11 (Fig. 3.2).
Chondrogenesis continues from day 7 to day 21, leading to the formation
of a cartilaginous callus that bridges and stabilizes the fracture site. By
nine days after fracture, the chondrocytes of the soft callus adjacent to the
woven bone of the hard callus begin to elongate, portions of the chondrocyte
membrane deliver calcium from the mitochondria into the extracellular
matrix in packaged units (matrix vesicles) and cells express chondroblastic
characteristics, as shown by the deposition of an extracellular matrix made
of type ii collagen and aggrecan.
• Proliferation
• Differentation
• Engraftment(days7-21)
Growth factors
pO 2
Stressapplied
Bone end
MSC
Cell fusion?
Celltrans-differentiation??
Differentiation
Trophicactivity
FB
CB
OB
￿ ￿ ￿ ￿ ￿
Matrixformation
Cartilageandosteoid(callus)
Ossiicationandmineralization
Bridgingoffracturegap
3.2 Atthesiteofbonefracturemesenchymalstemcells(MSCs)
undergodifferentiationundertheinluenceofmicroenvironmental
factors,suchaslowoxygentension,stressappliedtothebone,
includingmicromovementsandseveralgrowthfactorsexpressed
atdifferenttimepointsduringhealing.DifferentiationofMSCsto
connectivetissuelineagesgeneratesibroblasts(FB),chondroblasts
(CB)andosteoblasts(OB),whichactivelysynthesizeextracellular
matrixtobecalciiedandconvertedtobone.Besidesdifferentiating
capacity,arelevant'trophicactivity'ofMSCshasbeenrecently
hypothesized. 41
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