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 CW. Surfaces should be hydrophilic or very hydrophobic. 4
Example of gold standard Surface modification with PE derivative. PE-PP-PE, Pluronic Physical adsorption Chemical immobilization Short-time use Ex. Drug delivery Long-time use 5
ther strategies for hydrophilic surfaces 1 Albumin coating surface Phospholipid-mimicking surface + + + + Albumin - P - P - P - P Physical Hydrophobic adsorption chain Serum albumin: High water solubility and stability o affinity to proteins and platelets Hydrophilic phosphocholine head Hydrophobic acylchain 6
ther strategies for hydrophilic surfaces 2 Heparinized surface Endothelial cell attachment H - - C R S S 3 3 C- H H H H - - H HS - 3 S 3 HS HR- 3 Heparin: Immobilized covalently and ionically Inhibitor for thrombin or platelet adhesion atural blood vessel lining: Fibrinolytic activity (hydrolysis of fibrin) Plasma treatment Water soluble polymer H CH Will be discussed soon 7
R6 WT fibroblast adhesion triggered by RGD recognition Photos removed for copyright reasons. 500 µm H Peptide coupling RGD PCL-g-PE H H 2 PCL-g-PE+RGD H R6 WT: mice fibroblast bearing human integrin Arginine Glycine Aspartate Taniguchi, Polym Int. submitted R G D H 2 H H H H 8
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. 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. -H -SH -H 2 -CH=CH 2 -CH etc. 10
Protein/peptide immobilization strategies 1 Major reacting groups: -H 2 Activation of -H Cl C 2 R H 2 H C 2 C H R H Cl S 2 CH 2 CF 3 R S CH 2 CF 3 H 2 H R H Cl Cl Cl R H R 2 R H R R All the procedures must be carried out under anhydrous condition 11
Protein/peptide immobilization strategies 2 Major reacting groups: -H 2 Activation of -H 2 H 2 R H 2 H H H R Activation of -CH CH H R H 2 H C C R SCl 2 R H 2 H CH C Cl C R Be careful! 12
Protein/peptide immobilization strategies 3 Major reacting groups: -CH Activation of -H 2 H R CH Portein/peptide R 1 C R 2 + R 1 R C C carbodiimide H R 2 H + R 1 H 2 R C C H R 1 H R 2 H C R + C H R 2 13
Protein/peptide immobilization strategies 4 Chemoselective ligation Br R SH S R HS R C C S R HS R S R R C H 2 R R C R Reactions take place between selected pairs of functional groups 14
ther chemical surface modifications Preparation of hydrophobic and inert surfaces Fluorination H CF 3 CF 2 CF 3 CF 2 CF 3 H H Cl CF 2 CF 3 CF 2 H CF 2 CF 3 Silanization H Si Si Si H H H H H Si H H H Si H H Si 15
Summary: Clean a surface Reduce/eliminate protein/cell/bacteria adsorption, reduce thrombogenicity on-fouling and bioinert surfaces Promote biological response Immobilization of biomolecules Short time - Physical adsorption Long time - Covalent bonding 16