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
Surfaces should be hydrophilic or very hydrophobic.
4
Figure by MIT OCW.
Example of gold standard
Surface modification with PEO derivative.
PEO-PPO-PEO, Pluronic
Chemical immobilization Physical adsorption
Short-time use Long-time use
Ex. Drug delivery
5
Physical adsorption
- - - -
Other strategies for hydrophilic surfaces 1
Albumin coating surface Phospholipid-mimicking surface
N
+
N
+
N
+
N
+
Albumin
Hydrophobic chain
O O O O
O P O O P O O P O O P O
O O O O
O O O O
Serum albumin:
O O O O
Hydrophilic phosphocholine head
High water solubility and stability
No affinity to proteins and platelets
Hydrophobic acylchain
6
- -
Other strategies for hydrophilic surfaces 2
Heparinized surface Endothelial cell attachment
-
OR
O
-
COO
-
OSO
3
O
OH
O
O OH
OH
O
OH
O
OH
OSO
3
-
O
COO
O O
OH
NHSO
3
-
OSO
3
NHSO
3
O
-
Heparin:
NHR
Natural blood vessel lining:
Immobilized covalently and ionically Fibrinolytic activity (hydrolysis of fibrin)
Inhibitor for thrombin or platelet adhesion
Plasma treatment
Will be discussed soon
Water soluble polymer
OH COOH
7
500 m
NR6 WT fibroblast adhesion triggered by RGD recognition
Photos removed for copyright reasons.
O
N
O
OH
Peptide coupling
O
N
O
O
RGD
PCL-g-PEO+RGD
O O
PCL-g-PEO
HN
H
N
O
N
HN
O
NH
2
OH
NR6 WT: OH
mice fibroblast bearing human integrin
H
2
N
O
H
O
Arginine Glycine Aspartate
Taniguchi, Polym Int. submitted
R G D
8
Biomolecule immobilization method for specific surfaces
van der Waals
Electrostatic
Physical adsorption
Affinity
Adsorbed and cross-linked
Barrier system
Physical entrapment Hydrogel
Dispersed system
Soluble polymer conjugate
Covalent attachment Solid surface
Hydrogel
Biomolecules: proteins/peptides, saccharides, lipids, drugs,
ligands, nucleic acids/nucleotides, (cells,) etc. 9
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
-NH
2
-CH=CH
2
-COOH etc.
10
Protein/peptide immobilization strategies 1
Major reacting groups: -NH
2
Activation of -OH
O
O
O Cl C O NO
2
R NH
2
OH O C O NO
2 O C NH R
O
Cl SO
2
CH
2
CF
3
R NH
2
O S CH
2
CF
3
NH R OH
O
Cl
N
Cl NH R
Cl N
N
N N
R NH
2
O N OH
R
O N
N N
R R
11
All the procedures must be carried out under anhydrous condition
Protein/peptide immobilization strategies 2
Major reacting groups: -NH
2
Activation of -NH
2
N
O
O N
O
O
O
O
O
O
O
O
R NH
2
NH
2
N O N
H N N R
H H
O
Activation of -COOH
O
O
HO N
O
O
R NH
2
H
COOH
O
C O N
C N R
O
O O
R NH
2
SOCl
2
H
COOH
C Cl C N R
Be careful!
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Protein/peptide immobilization strategies 3
Major reacting groups: -COOH
Activation of -NH
2
H
R
1
N C N R
2 O N
+
R
1
R COOH
R C O C
Portein/peptide
carbodiimide
HN R
2
H
O N
+
R
1
R C O C
O HN R
1
HN R
2
H
N C R + O C
HN R
2
NH
2
13
Protein/peptide immobilization strategies 4
Chemoselective ligation
Br R
SH S R
HS R
O C O C S R
O O
O O
S R
HS R
N N
O O
R R
H
2
N O R
C N O R C
O
Reactions take place between selected pairs of functional groups
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Other chemical surface modifications
Preparation of hydrophobic and inert surfaces
Fluorination
CF
2
CF
2
O
CF
2
O
CF
2
O
O
CF
3
O O
OH
CF
3 CF
3
O
OH Cl CF
2
CF
3
O
CF
3
OH
OH
O
Silanization
OH
O
O Si
O Si
O
O
O Si
O Si
OH O
OH O
OH O
OH
OH
O Si
OH OH O
O Si
OH
OH
OH
15
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
16