Micro/Nanoporous Scaffolds

for Tissue Engineering

Applications
Department of Chemical Engineering and Materials Science
Amrita School of Engineering
Coimbatore – 641 105
January 2009
 First Review
By
Divya Haridas (CB105PE012)
Karthikeyan G (CB105PE023)
Krishna Priya C (CB105PE025)
Premika G (CB105PE028)

Guide
Dr. Murali Rangarajan. Ph.D

Co-Guide
Dr. Nikhil K Kothurkar. Ph.D
 Scaffolds-Overview
 Scaffolds play a critical role during cell adhesion,
proliferation and differentiation
 Cell Adhesion occurs between cell membrane and
the implanted scaffold surface via the receptor-
ligand bonds
 Following implantation, the gradually degrading
scaffolds is continuously subjected to load due to
the growing tissues
 Effect of stress – detachment of bonding forces -
undesirable
 However, little is known of the interaction
between the scaffold and the bone
 Need for Modeling
 Once implanted, there is only very limited
access to the adhered scaffolds
 Any control over the healing response is
also lost upon implantation
 Surgical intervention to possibly re-
engineer any treatment also would prove
to be an invasive procedure
 At this point, the scaffold modeling
process takes over, modifying the design
and mechanical characteristics of the
scaffold on its own
 Cell Adhesion
 Cell adhesion is
the binding of cell
to another cell or
to a surface or
matrix

 Cell adhesion is
regulated by
specific cell
adhesion
molecules that
interact with other
molecules
 Cell adhesion on Biomaterials
 The adhesion involves two phases – the
attachment phase and the adhesion phase
 Attachment phase – involves short term events
like physicochemical linkages between cells and
materials involving ionic forces, van der Walls
forces, etc.
 Adhesion phase – involves long term events like
interaction between extracellular matrix proteins,
cell membrane proteins and cytoskeleton proteins
 Protein interactions with ligands, other proteins,
or surfaces are controlled by the complex array of
intermolecular and intersurface forces
 Peeling Model
 Assumes attachment pattern similar to that of
peeling

 Simple model that captures essential physics

 The model consists of two regions

1. the free zone and 2. the adhesive zone

 General approach
 Analyze the membrane mechanics for each
zone separately
 Requires continuity of the solutions at the
interface between the two zones
One Dimensional Peeling Model

Evan A. Evans, 1985. Detailed mechanism of membrane-

membrane adhesion and separation, Biophysical Journal, 48,
175-183
 Peeling Model - Assumptions
 Scaffold Membrane
 Rigid, flat, non-porous, solid surface

 Cell Membrane
 Thin elastic shell, Axisymmetric

 Forces of separation = Tension induced during

adhesive contact formation.

 The adhesion forces are finite range interactions

Hence membrane is studied under two zones
 Peeling Model- Forces
Forces
 A cell membrane adhered to the scaffold will be
subjected to a combination of internal and external
forces
 External forces acting includes

 Ligand-receptor Interactions ( Major Force)

 Electrostatic interactions at the surface

(Approximated)
 van der Waals forces of attraction (Approximated)
 Steric forces of repulsion (Approximated)

 The shape of the cell is then obtained by solving for

the internal forces when the cell is subject to the
external forces, at equilibrium
Leckband D., 2000. Measuring the forces that control
protein interactions, Annual Review Biophysics Biomolecular
Structure 29, 1-26
One Dimensional Peeling Model

Dong Kong, Baohua Ji, Lanhong Dai, 2008. Nonlinear

mechanical model of cell adhesion, Journal of
Theoretical Biology 250, 75-84
 Peeling Model
 The forces acting is given as an empirical formula
:
Linear :

fn - strength of the bond

lb - bond length

Nonlinear :

L - bond extension
C - dimensionless parameter characterizing the nonlinearity of
force–extension relationship of bond and the ability of bond
Evan having
A. Evans, 1985.
large Detailed mechanism of membrane-membrane adhesion and
deformation
separation, Biophysical Journal, 48, 175-183
 Governing Equations

Free Adhesive Zone

Zone

Where
s = arc length f = adhesive bond force of a single
bond
k= local curvature n = bond density
 Solution for free zone – Linear and
Boundary Conditions
Non Linear

Changing the variables from Ɵ to X we get

Boundary
Conditions
 Solution for free zone – Linear and
Non Linear
The solutions of free zone are functions of local angle θ, the external force Tex ,
the Macroscopic angle θ0 is shown as follows

The elastic constitutive relation for membrane is given by bending moment is

proportional to the change in curvature

Where km0 is stress free curvature B – bending modulus

The local balance of moments in the membrane surface is given by the

relation transverse Shear equal to gradient bending moment

Free zone curvature :

 Solution for adhesive zone - Linear
 Tangential forces remains the same but normal
forces gets modified
 fn is the sum of the attractive and repulsive
forces
 Fn is the maximum force at which the bond will
break
 Bond length scale lb is the maximum stretch
required to reach the peak force
 Solution for adhesive zone - Linear
 The work done in either breaking or forming the
cross bridges when the membrane is brought
from large separations to equilibrium contact is
given as

 Adhesion energy per unit contact area is given as

 Solution for adhesive zone - Linear
 Adhesive stress

 When the membrane angle is less than θ ≤ 30°

 Solution for adhesive zone - Linear

 Solving
 Solution for adhesive zone
 Variation in tension term is of higher order i.e.
smaller compared to bending stress term

 Where,

Ɵα - ratio of adhesion and bending energies

t - ratio of tension and bending
 Solution for constants
 At the edge of contact zone i.e. s = 0 and = lb
 C2 / =1
 Θ= 1 C2 - 2 C1
 K=- 1
2
C2 + 2 1 2 C1 + 2
2
C1
 Q/B = [( 2
2
- 1
2
) 1 +2 1 2 ]C2 +
2

[( 1
2
- 2
2
) 2 +2 2 1 ]C1
2

 C1 value is solved using Newton’s method and

values are obtained from a C program
 Adhesion energy per unit area vs ratio of
adhesion to bending (deformation) energies
Picture 11

The approximation that tension T is constant is reasonable for:

large bending (small θ ) and strong adhesion (large θ0)
 Contact Angle (θ0) vs.
Adhesion/Bending Energy (θα)

Contact angle is large when adhesion is strong and free

contact angle is large
 Future work
 Linear Model
 Obtain the contour of the cell membrane as
function of
 Bending Modulus

 Tension

 Adhesion

 This translates as obtaining contour of the cell

membrane as a function of
B

Θ
0


 Future work
 Adhesive zone – Nonlinear Modeling :

 From experimental data on osteoblast adhesion on

scaffolds, find a nonlinear force-extension model

 Use this model to obtain equilibrium adhesion profiles of

osteoblasts on flat scaffold surfaces

 Extend this model to curved scaffold surfaces

Thank you