Lecture 9:
Surface Modification of Biomaterials
Supporting notes
3.051J/20.340J Materials for Biomedical Applications,
Spring 2006
1
Purpose:
Alter surface properties to enhance performance in
biological environment while retaining bulk properties
of device
The modified zone at the surface of the device should be
as thin as possible. Ideally < 1 nm
2
Specific objectives:
1. Clean a surface
2. Reduce/eliminate protein adsorption
3. Reduce/eliminate cell adhesion
4. Reduce bacterial adhesion
5. Reduce thrombogenicity
6. Promote cell attachment/adhesion
7. Alter transport properties
8. Increase lubricity
9. Increase hardness
10. Enhance corrosion/degradation resistance
3
Preparation of non-fouling surfaces
to prevent non-specific protein/cell or bacterial adhesion
to reduce thrombogenicity
Figure by MIT OCW.
Surfaces should be hydrophilic or very hydrophobic.
4
Example of “gold standard”
Surface modification with PEO derivative.
PEO-PPO-PEO, Pluronic
Physical adsorption
Chemical immobilization
Short-time use
Ex. Drug delivery
Long-time use
5
Other strategies for hydrophilic surfaces 1
Albumin coating surface
Phospholipid-mimicking surface
N+
N+
N+
N+
Albumin
O
-O
O
P
O -O
O
P
O -O
O
O
O
O
P
O -O
O
O
O
O
O
O
O
O
P
O
O
Hydrophobic
chain
Physical
adsorption
Serum albumin:
High water solubility and stability
No affinity to proteins and platelets
Hydrophilic phosphocholine head
Hydrophobic acylchain
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Other strategies for hydrophilic surfaces 2
Heparinized surface
OR
O
COO­
O
OSO3O
O
OH
OH
COO-
OSO3O
O
O
OH
OH
OH
NHSO3
-
OH
O
O
O
NHR-
Endothelial cell attachment
OSO3-
NHSO3
-
Heparin:
Natural blood vessel lining:
Immobilized covalently and ionically
Inhibitor for thrombin or platelet adhesion
Fibrinolytic activity (hydrolysis of fibrin)
Plasma treatment
Water soluble polymer
OH
COOH
Will be discussed soon
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NR6 WT fibroblast adhesion triggered by RGD recognition
Photos removed for copyright reasons.
500 µm
O
O
N
OH
Peptide coupling
O
N
RGD
O
O
O
PCL-g-PEO
PCL-g-PEO+RGD
O
HN
NH2
HN
NR6 WT:
mice fibroblast bearing human integrin
Taniguchi, Polym Int. submitted
O
H
N
H2N
O
N
H
OH
OH
O
O
Arginine Glycine Aspartate
R
G
D
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Biomolecule immobilization method for specific surfaces
Physical adsorption
Physical “entrapment”
Covalent attachment
van der Waals
Electrostatic
Affinity
Adsorbed and cross-linked
Barrier system
Hydrogel
Dispersed system
Soluble polymer conjugate
Solid surface
Hydrogel
Biomolecules: proteins/peptides, saccharides, lipids, drugs, ligands, nucleic acids/nucleotides, (cells,) etc.
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Chemical modification of materials
ref. Ratner, Biomaterials Science, p. 229
For covalent binding to an inert solid polymer surface, the
surface must first be chemically modified to provide
reactive groups for the subsequent immobilization step.
-OH
-SH
-NH2
-CH=CH2
-COOH
etc.
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Protein/peptide immobilization strategies 1
Major reacting groups: -NH2
Activation of -OH
O
Cl C O
O
NO2
OH
R
O C O
NO2
O
NH2
O
C
NH R
O
Cl
OH
SO2CH2CF3
R
O
S
CH2CF3
NH2
NH R
O
Cl
N
Cl
Cl
N
N
N
OH
R
N
O
NH R
R
NH2
N
N
O
N
N
R
All the procedures must be carried out under anhydrous condition
R
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Protein/peptide immobilization strategies 2
Major reacting groups: -NH2
Activation of -NH2
O
N O
NH2
O
O
O
O
O
O
O N
O
R
N
H
O N
NH2
N
H
N
H
O
Activation of -COOH
O
O
HO N
O
COOH
O
R
C O N
NH2
O
C
H
N
R
H
N
R
O
O
COOH
SOCl2
Be careful!
O
R
C
Cl
NH2
C
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R
Protein/peptide immobilization strategies 3
Major reacting groups: -COOH
Activation of -NH2
H
R1
R
N
C
N
R2
N+ R1
O
COOH
R
carbodiimide
Portein/peptide
C
O
C
HN
R2
H
N+ R1
O
R
C
O
C
O
HN
NH2
R2
H
N
C
HN
R
+
O
R1
C
HN
R2
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Protein/peptide immobilization strategies 4
Chemoselective ligation
SH
O
C
Br
R
HS
R
S
R
O
C
O
R
O
O
O
HS
S
R
N
N
O
O
R
C
S
H2N
O
O
R
R
R
C
N
O
R
Reactions take place between selected pairs of functional groups
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Other chemical surface modifications
Preparation of hydrophobic and inert surfaces
O
Fluorination
O
OH
OH
CF2
Cl
CF3
OH
OH
O
O
CF2
O
O
CF2
O
O
CF2
O
CF2
CF3
CF3
CF3
CF3
Silanization
OH
O
O Si
OH
O
O
Si
O
Si
OH O
OH O
OH
OH
O
OH
OH
OH
OH
O
O Si
Si
OH O
O
Si
O
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Summary:
· Clean a surface
· Reduce/eliminate protein/cell/bacteria adsorption,
reduce thrombogenicity
Non-fouling and bioinert surfaces
· Promote biological response
Immobilization of biomolecules
Short time - Physical adsorption
Long time - Covalent bonding
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