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Transcript of Biomaterials and Protein Adsorption. Examples of Biomaterials Medical implants Contact lenses Drug...
![Page 1: Biomaterials and Protein Adsorption. Examples of Biomaterials Medical implants Contact lenses Drug delivery systems Scaffolding for tissue regeneration.](https://reader035.fdocuments.in/reader035/viewer/2022062407/56649e2e5503460f94b1e138/html5/thumbnails/1.jpg)
Biomaterials and Protein Adsorption
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Examples of Biomaterials
• Medical implants • Contact lenses• Drug delivery
systems• Scaffolding for
tissue regeneration
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Proteins are amphiphilic molecules in an aqueous
milieu• Polypeptides are
amphiphilic molecules• BUT -- The human
body is 90% water!• SO : hydrophobic
regions of proteins seek refuge in supramolecular configurations that minimize their exposure to water
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Hydrogen Bonding Depends on the Electronegativities of the Donor and
Receptor Groups
H2N CH C
CH2
NH
O
C
NH2
O
CH C
CH2
NH
O
SH
CH C
CH2
OH
O
CH CH3
CH3
• Blue = hydrogen donors
• Red = hydrogen acceptors
• Black = non-hydrogen bonding
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Proteins adhere to hydrophobic surfaces
t
•“Foot Model” of protein adhesion•Self-propagating•First step in the humoral response against foreign materials in the body
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Design of Biomaterials Surfaces
• Hydrophilicity inhibits protein adsorption, however:
• Some cell adhesion may be desirable
• Compliance is a key consideration
• Solution? Polymers, of course!
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Techniques for Coating Biomaterials
• Physisorption– Adhesion to biomaterial
surface is of hydrophobic and/or electrostatic origin
• Chemisorption– Polymer is chemically
attached to the surface, usually via reaction of the surface with a specific end-group on the polymer
– Often referred to as a “self-assembling monolayer” (SAM)
example: an –SH terminated polymer covalently binds to a Au3+ surface
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Polymer Brushes
• A “brush” is formed when the spacing d between end-grafted polymers is less than twice the Flory radius, RF, where RF ~ aN3/5 and a is the monomer size
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Fundamentals of Protein-Surface Interactions
• Large free energy gain associated with protein adhesion to hydrophobic surfaces
• Attraction due to long-range van der Waals forces, as well as specific and hydrophobic interactions, and the electrostatic double layer (all short-range)
• Repulsion due to steric and osmotic factors (short range)
• Proteins will stick if Ubare(0) < kT
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Steric and Osmotic Factors
• Atoms and molecules take up a finite amount of space which cannot be occupied by other elements – i.e. they introduce an excluded volume– Dense packing, rotations, and/or
rearrangements may therefore not be energetically allowed: i.e. steric hindrance
– Crowding leads to an increase in the internal energy and thus the osmotic pressure
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The Free Energy Profile of the Brush has Two
Minima
a) brush potential, Ubrush(z)
b) attractive [primarily] van der Waals
potential UvdW(z)
c) net interaction potential
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Modes of Protein Adsorption
solid substrate
e.g. human serum albumin7
(IV.)
(I.)
Loend-grafted
polymer brush
s
RP
RP(III.)(II.)
(I.)
adsorbed proteins
(I.) adsorption of proteins to the top boundary of the polymer brush
(II.) local compression of the polymer brush by a strongly adsorbed protein
(III.) protein interpenetration into the brush followed by the non-covalent complexation of the protein and polymer chain
(IV.) adsorption of proteins to the underlying biomaterial surface via interpenetration with little disturbance of the polymer brush
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What do the The Primary and Secondary Minima
Correspond to?
Primary minimum: Uin
adsorption at the solid surface
Secondary minimum: Uout
Adsorption at the outer brush surface
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Osmotic vs Entropic Forces
The brush thickness, L depends on a balance of forces:
Osmotic Force
2
kT
a 3
L
Na
3
where
So the correspondingforce and free energy per chain:
Elastic Force
2Na
L
kT
f el
31
2
a
Na
L
At Equilibrium
32
23
a
L
Na
34
33
a
kT
a
And the corresponding osmotic pressure:
Monomer volume fraction:
Brush thickness:
Variables:
pressure osmotic
fraction lumemonomer vo
sizemonomer
chainper area
a
osmf
LFosm
2
2
Na
L
kT
Fel
elosm ff 0
L
For
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Secondary Adsorption
• Since there is no energy barrier, it is only possible to control Uout thermodynamically
• Uout UvdW(L)• Because penetration of the brush requires chain
compression, large proteins will preferentially undergo secondary adsorption so long as UvdW(L) < -kT
• For a rod-like protein (fibrinogen, e.g.) of radius R and length H, suppression of secondary adsorption may only be achieved if:
Occurs when Uout < -kT
32
313
2
HR212
AL
Where A is the Hamaker constant, A ~ 10-21 J
for proteins interacting with organic materials
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Primary Adsorption
When Rp << L :3
PPbrush RVU
LzFosm )(
L
Naz
3
)(
When Rp >> L :
kT
azz
3)()(2 where
There is negligible effect on
Approach to the surface results in compression of the brushand an increase in osmotic pressure
and
Occurs when Uin < -kT
The rate constant for adsorption:
kT
U
L
Dkads
*
exp
Where is the width of the energy barrier and D is the diffusion coefficient
And the free energy barrier, U* for primary adsorption:
33
R
kT
R
kT
U *
Where Uads is the interaction potential of the adsorbed protein at the bare surface
*UUU adsin Finally:
** The presence of an energy barrier enables both thermodynamic and kinetic control
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Methods for Counteracting Protein-
Surface Interaction with Polymer Coatings
• Dense polymer coatings (low )
• Long polymer chains (large N)
d
R N
Uout may be manipulated by varying N or Uin is primarily controlled by varying
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Poly(ethylene oxide) (PEO)
in Biomaterials• The most extensively used
polymer for biomaterial surface coatings, because:– Completely water-soluble– Creates an extensive H-
bonding network– Helical conformation– Proven to be extremely protein
resistant– Capable of being functionalized
for ligand-receptor specificity
• However: – Poor mechanical stability– Protein adhesioin reported
under certain conditions
O
O O
H HO
O O
OH
HO
H
HO