Lecture 9: Surface Modification of Biomaterials Supporting notes 3.051J/20.340J Materials for Biomedical Applications, Spring 2006 1Purpose: 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 2Specific 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 3Preparation 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 immobilizationPhysical adsorption Short-time use Long-time use Ex. Drug delivery 5Physical 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-OSO3 O OH O O OHOH O OH O OH OSO3 -OCOOOO OH NHSO3-OSO3 NHSO3 O -Heparin: NHRNatural blood vessel lining: Immobilized covalently and ionically Fibrinolytic activity (hydrolysis of fibrin) Inhibitor for thrombin or platelet adhesion Plasma treatment Will be discussed soonWater soluble polymer OH COOH 7500 µmNR6 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 OO PCL-g-PEO HNHNONHN O NH2 OH NR6 WT: OH mice fibroblast bearing human integrin H2N O H O Arginine Glycine AspartateTaniguchi, Polym Int. submitted R G D 8Biomolecule immobilization method for specific surfaces van der Waals ElectrostaticPhysical 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. 9Chemical 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. 10Protein/peptide immobilization strategies 1 Major reacting groups: -NH2 Activation of -OH O OOCl C O NO2 R NH2 OH O C O NO2 O C NH R O Cl SO2CH2CF3 R NH2 O S CH2CF3 NH ROH O Cl N Cl NH RCl N N N NR NH2O NOH R O N N N RR 11All the procedures must be carried out under anhydrous conditionProtein/peptide immobilization strategies 2 Major reacting groups: -NH2 Activation of -NH2 NOONO OO O O OO O R NH2 NH2 N O N H N N R H H O Activation of -COOH O OHO N OO R NH2 HCOOH O C O N C N R O O O R NH2SOCl2 HCOOH C Cl C N R Be careful! 12Protein/peptide immobilization strategies 3 Major reacting groups: -COOH Activation of -NH2 H R1N C N R2 O N+R1 R COOH R C O C Portein/peptide carbodiimide HN R2 H O N+ R1 R C O C O HN R1 HN R2 H N C R+ O C HN R2 NH2 13Protein/peptide immobilization strategies 4 Chemoselective ligation Br RSH S R HS R O C O C S R O O O O S RHS R N N OO RR H2N O R C N O RCO Reactions take place between selected pairs of functional groups 14Other chemical surface modifications Preparation of hydrophobic and inert surfaces Fluorination CF2CF2O CF2O CF2O O CF3O OOH CF3CF3 OOH Cl CF2 CF3 O CF3 OH OH O Silanization OH O O Si OSi O O O SiOSi OHO OH O OH O OH OH O Si OH OH O O Si OH OH OH 15Summary: · 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