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ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

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where n p is the number of proliferating chondrocytes per unit time (cells/day) and<br />

h max is the maximum height, in μm, of the fully mature hypertrophic chondrocytes.<br />

d) Based on the mathematical model proposed by Garzón-Alvarado et al [12] the<br />

growth rate can be written as:<br />

where<br />

proliferation<br />

d and<br />

proliferat ion hypertroph y<br />

& , (4)<br />

ε = d + d<br />

hipertrophy<br />

d are the strain rate tensors due to proliferation and<br />

hypertrophy, respectively. The growth in the proliferative zone is due to cellular<br />

mitosis, therefore it is given by<br />

⎛ ⎞<br />

proliferation<br />

d ⎜<br />

dn<br />

= n ⎟n<br />

⊗n<br />

⎜ p ,<br />

⎟<br />

(5)<br />

⎝ lp<br />

⎠<br />

where d n is the width of the chondrocyte in the preferential direction of growth n,<br />

and l P is the width of the proliferative zone. Furthermore, the growth in the<br />

hypertrophic zone is due to the elongation experienced by the cells during their<br />

differentiation from the proliferative state (ovoid) to the hypertrophic state (quasispherical<br />

shape) [12]:<br />

⎛<br />

⎞<br />

hypertrpohy<br />

d ⎜<br />

2 ⎛ R ⎞<br />

i(<br />

t)<br />

− s<br />

= ⎟<br />

⎜ ∑ ⎜<br />

⎟<br />

⎟<br />

n ⊗n<br />

, (6)<br />

⎝ lh<br />

i∈C ⎝ Δt<br />

H i ⎠⎠<br />

where Ri (t)<br />

is the instantaneous radius of the i-th chondrocyte in the growth<br />

direction once the cell begins to differentiate, s is the minor radius of the<br />

proliferative chondrocyte ( d n = 2s<br />

), l h is the width of the hypertrophic zone and<br />

Δ ti<br />

is the hypertrophy elapsed time. This time is limited by the maximum<br />

chondrocyte maturation time t E [12].<br />

e) According to Stokes et al [7] the final size of the hypertrophic chondrocytes is<br />

mechanically modulated, so we assume that the instantaneous radius is a function of<br />

the stress modulation over the preferential direction of growth Δ σ n :<br />

where<br />

n<br />

R<br />

( Δσ<br />

) − s<br />

( 1+<br />

αΔσ<br />

)<br />

− s<br />

Ri ( t)<br />

= s + max<br />

tE<br />

n Δti<br />

= s +<br />

n<br />

tE<br />

f<br />

max Δti<br />

Δ σ = σ −σ<br />

is the difference between the current stress over the preferred<br />

n<br />

f<br />

n<br />

f f<br />

direction of growth σ n and the stress under physiological conditions σ n , Rmax is<br />

the radius of the sphere representing the hypertrophic chondrocyte achieved under<br />

physiological loading conditions ( Rmax hmax<br />

2<br />

f<br />

= ) and α is the change in the<br />

maximum size of chondrocyte per unit stress. α is calculated using experimental<br />

data [6]<br />

R<br />

(7)

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