Webinar at DIT Dehradun

Overview of Fluid Mechanics and Its

Applications in Physiological Flows

Dharmendra Tripathi
Associate Professor, Mathematics
National Institute of Technology Uttarakhand
Srinagar, Pauri Garhwal, Uttarakhand –
246174
Email: dtripathi@nituk.ac.in
 Canalicular Fluid flow model in Bone Adaption

In Silico Ex Vivo Experiments

Modelling
Wistar Rat
Mathematical Modelling Micro-CT Scan

In Vivo Loading Flow Geometry

• Loading (Sinusoidal, Trapezoidal, Boundary Conditions Proximal

Triangular, Sawtooth) Based on In vivo Mid-diaphysis

• Frequency Loading
Distal
• Rest insertion between load cycles
Poroelasticity
for Estimation
C57BL/6J Mice Bone Morphology Analysis
Fo sin t of Pore-Pressure
y a
x
Nanoindentation
z
Flow Analysis
1.8 mm Distal
end free
Proximal a' 5 mm
end fixed
Computational Solution

Permeability Measurement/
Results and Discussion Dynamic Measurement
Analysis
Bone Adapts According to Demand!
Cell Regulates Bone Adaptation..!!
 Bone gain vs. bone loss

Tennis player using Physically Challenged :[b] 25-30% bone mass

Bo [a]
his forearm reduction during
ne Bo six months
Gai ne exposure to
n Los microgravity [c]
s

Dominant arm

Non-Dominant arm
CT scan of a 26-year-old male tennis player. Paired slices, from left to right, are
the proximal humerus, humeral shaft, and distal humerus. Upper panel:
dominant arm; lower panel: nondominant arm (Source: BoneVol. 27, No. 3, pp.
Spinal cord injury:[d] Bed ridden patients:[e
351–357)
 Consequences!

Increase in
Porosity [f]

Bone Fractures [h]

Reduced cortical
thickness [g]
 Solutions?

vs.

Pharmaceutical drugs [i] Physical exercises [j]

• Low-amplitude, cyclic mechanical loading may inhibit bone loss.

• “How” and “where” to stimulate to maximize osteogenic response for cure, are required to
addressed.
• The relationship between loading induced mechanical environment and site-specific new bone
formation is less clear.
Animal Loading Models on Bone Adaptation
Canalicular fluid flow in a Lacuno-canalicular system (LCS) of bone to
examine the effect of transport of signalling molecules

Fig 5.1: a) Cantilever bending model of mice tibia, (b) loading configuration based
on Srinivasan et al. (2002), (c) mid-diaphyseal cross section of mice tibia, (d) curvy
canaliculus channel used for fluid flow analysis.

NO molecule Adenosine-5’-Triphospate (ATP) Prostaglandin E2 (PGE2)

Pore-pressure estimation

The solution provides pore-fluid pressure as a sum of steady-state and transient

responses mentioned in Kameo et al. (2009) out of which transient pore-pressure for
cantilever bending is computed as:

n2 sinh n (cosh n  cosh(n y * ))  n2t*
P *
 2 e
   
Transient
n 1 ( n
4
  2
)( n  sinh n cosh n )

n2 (sin n  n cos  n )( y * sin  n  sin(  n y * ))  n2t*
 6 e
n 1 (  4
n   2
)(  2
n   n sin  n cos  n  2sin 2
 n )

Fluid flow analysis

Pericellular fluid is assumed as an incompressible and isothermal Newtonian fluid. Now,
the mass conservation equation and Cauchy’s momentum equation are used to compute
fluid flow in the canaliculus as follows (Tripathi 2012; 2013):
u f v f
 0
y x
    P   2u f  2u f  uf
 f   vf  uf u
 f      2  2 
 
 t x y  y   y  x  kc
 The slip boundary conditions are considered as:

uf x  h1
 0, uf x  h2
0

Non-dimensional solution is obtained

1
to compute
1
axial fluid velocity as follows:
x*  x*
P*
u ( y , x )  C1e  C2  kc *
' * * kc kc

y
f

Molecular Transport
The governing equations employed to define the motion of the particles are
(Jiménez-Lozano et al. 2009; Johnson 2016):
  p d p3  u p   p d p3  v p
  3 d p  u f  u p           3 d p  v f  v p 

6

t  6  t
   
c  p d p2
Following non-dimensional parameters where Sn   
18 l 2
are introduced in above equation
Now equation is subjected to boundary
u p Rm2 v pl 2 u f Rm2 vf l2
u 'p  , v 'p  , u 'f  , v 'f  , t* 
ct condition
Q Q Q Q l2
u 'f t* 0
 0, and v ' f t* 0
0
This modifies the equations
   
*
t *
t
 
u 'p v 'p u p  u f 1  e Sn
' '
 v p  v f 1  e Sn
' '
 
t*
1

   u 'f  u 'p
Sn
 t *
1
Sn

   v 'f  v 'p  







 Signaling Molecules of Interest

Diffusion
Free Molecular
Molecular coefficient Hydrodynamic
Diffusion Density Stoke’s number
Molecule Structure Weight measured in Diameter
bone LCS
Coefficient ( p ) ( Sn)
(dp )
( D free )
( DLCS )
Units (Da) (micorn 2 /sec) (μm 2 /sec) (nm) (kg/m 3 )
Adenosine-5’-
Triphospate
507 275.63 502 0.82 1040 4.19  108
(ATP)

Prostaglandin E2
(PGE2) 352 297 540 0.76 873.8 3.029  108

Nitric Oxide
30 353.42 644 0.63 1.3402 3.19  1011
(NO)
 Results and Discussion
Transient Pore-Pressure Distribution

Normalized transient pore-pressure distribution with respect to the Normalized transient pore-pressure
normalized position at different frequencies with respect to the normalized time
 Results and Discussion
Canalicular Fluid Flow Characteristics
10-3
6

u' f
3 y* = 0.5
y* = 0.4
2 y* = 0.3
y* = 0.2
1
y* = 0.1
0
1 1.5 2 2.5 3
*
y

(a) k 10
c
17

(e) (i) (m)

Ω = 1 Hz

x* x* (j) x* (n) x*
(b) (f)
Ω = 3 Hz

(c) x* (g) x* (k) x* x*

(o)
Ω = 5 Hz

x* x* (l) x* x*
(d) (h) (p)
Ω = 10 Hz

x* x* x* x*

Normalized transient fluid velocity with respect to the normalized location at different axial distance
 Results and Discussion
Canalicular Fluid Flow Characteristics
(a) (b)

0.3

0.2
f
u'

0.1

0
3
1
2 0.5
y* 1 0
x*
t* x*
(a) (b)
y* = 0.1 y* = 0.2
(c) (d) 0.3

0.2

u' f
0.1

0
3
1
2 0.5
y* 1 0
x*
t* x*
y* = 0.1 y* = 0.2
(c) (d)

x* x*

x* x* y* = 0.3 y*= 0.4

(e)
y* = 0.3 y*= 0.4

(e)

x*
y* = 0.5

x*
y* = 0.5

A three-dimensional plot of transient fluid velocity with respect to normalized time and normalized
location at different axial location 4
7
 Results and Discussion
Streamlines (Trapping)
x
(a) (b)
y

  10

(c) (d)

Streamlines of canalicular fluid motion at different frequency

4
8
 Results and Discussion
Signalling Molecule Transport: Effect of Loading Frequency

1 Trajectories of ATP (a, b, and c), PGE2 (d, e, and f) and NO (g, h, and i) molecules located at
( y  0.15and x  1.1 ) for different time intervals [0 0.1], [0 0.5], and [0 1].
* *
2
 Results and Discussion
Signalling Molecule Transport

1 Trajectories of (a and b) ATP, (c and d) PGE2, and (e, f) NO molecules: (a, c and e) near cell
2 process ( y*  0.05 and x*  0.8 ), and (b, d, and f) near canalicular wall (
* *
 Results and Discussion
Small Molecule Moves Faster

Comparative trajectories for ATP, PGE2 and NO molecules at spatial locations

( y*  0.15 and x*  1.1 ) with different frequency (a)   1 ; (b)   3 ; and (c)   10
 Conclusions
The conclusions are as follows:

 Particle trajectories indicate that small molecule moves faster as compared to large
molecule with in the canalicular fluid flow.
 Transport behaviour will allow us to design effective guidelines for the formulation of
drugs to ensure effective transport in bone tissue.
 Inhomogeneous flow behavior is observed at higher loading frequency which could
be the possible explanation for amplified mechanoresponsive observed at higher
frequency.

 Trapping of molecules may saturate the mechano-response at higher loading

frequency.

 Molecules trajectories may be utilized in design of biomechanical interventions in

combination with pharmaceutical agents to improve the bone health.
 References

Image sources:
a) http://topnews.in/sports/files/Leander-Paes-16.jpg
b) http://www.empoweryourhealth.org/sites/all/themes/empower/vol2issue3/images/page16-top.jpg
c) http://www.masterfile.com/stock-photography/image/640-01354672/Physically-challenged-senior-man-walking-on-
a-treadmill
d) http://www.injurylawyer.com/wp-content/uploads/2012/09/spinal_cord_injury_lawyer.jpg
e) http://www.thehindubusinessline.com/news/science/countdown-begins-for-sunita-williams-expeditions-
return/article4097776.ece
f) http://www.iofbonehealth.org/what-is-osteoporosis
g) http://depts.washington.edu/osl/Botox_files/Picture%202.png
h) http://fxrxinc.com/blog/wp-content/uploads/2013/02/Femur-fracture-4.jpg
i) http://www.examiner.com/article/osteoporosis-drugs-like-fosamax-and-boniva-linked-to-hip-fractures
j) http://club-fitness.net/wp-content/uploads/2016/05/ejercicios-1.gif

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THANK YOU FOR YOUR KIND ATTENTION !