13.051J/20.340J Lecture 9: Surface Modification of Biomaterials Purpose: alter surface properties to enhance performance in biological environment while retaining bulk properties of device Specific Objectives: 1. clean a surface 2. reduce/eliminate protein adsorption • reduce undesirable/uncontrolled responses to implants & extracorpeal devices C3b/IgG adsorption ⇒ activation of WBCs • reduce nonspecific adsorption on biosensors & bioassays Source: Wikipedia (Gray's Anatomy)(noise & fouling) • current strategy: hydrated, hydrophilic surfaces PEO is current “gold standard” 3. reduce/eliminate cell adhesion • create surfaces that mimic nature’s cell resistant surfaces ex. Human serum albumin: naturally low affinity to components of body fluids & tissues (consider its high conc. in blood—60 wt% of proteins!)2 3.051J/20.340J 4. reduce thromogenicity • hydrophilic surfaces - eliminate protein adsorption • hydrophobic surfaces - inherently weak surface/cell interface - exploits shear stress due to blood flow • surface-bound heparin - natural surface of endothelial cells lining blood vessels - inactivates factor Xa & thrombin by binding anti-thrombin • surface-bound albumin - no ligands for platelets (can attach if HSA denatures-how?) • albumin affinity coatings - surfaces that strongly adsorb albumin from blood to make a passive coating; ex. bilirubin Kd ~ 10-8 l/mol • endothelial cell attachment - natural blood vessel lining ⇒ fibrinolytic activity (hydrolysis of fibrin)33.051J/20.340J 5. reduce bacterial adhesion “fimbriae” or “pili” (~1 µm)Bacterial adhesion ¾ via proteins & polysaccharides in cell wall (nonspecific) ¾ specific receptors for plasma proteins (ex. S. aureus binds fibrinogen/fibrin, FN, VN) ¾ pili facilitate initial surface attachment bacteria cell wall ex. E. coli bacteria cell wall (gram negative) (gram positive) ex. Staphylococcus aureus,proteins peptidoglycan S. epidermis lipopolysaccharide • passive coatings hydrophilic polymers, HSA, • bactericidal agents - Ag-containing films - antibiotics (ex., gentamicin eluting film) - cell wall-disrupting agents (cationic) i) non-mammal anti-microbial peptides: amphiphilic helix structures (ex. LKLLKKL) ii) cationic polymers (ex. lipid-like side chains)4 3.051J/20.340J 6. promote cell attachment/adhesion • modify γ1 (vary chemistry ⇒ ↑ protein adsorption) • create positive surface charge - many proteins have net negative surface charge ⇒ ↑ protein adsorption - cell glycocalyx has neg. charge ⇒ nonspecific attraction + + + + + + + + + + + + + + + + + + NOTE: a strongly ++ surface can inhibit cell growth • increase surface roughness/porosity - promotes cell attachment (↑ surface area for binding) - can inhibit cell growth • bind cell adhesion ligands to surface - adhesion proteins (fibronectin) - adhesion protein epitopes: RGD (fibronectin, collagen…); YIGSR(tyr-isoleuc-gly-ser-arg) (laminin B1)5 3.051J/20.340J 7. alter transport properties - regulate the passage of H2O, theraputic agents, etc. ex. crosslinking (passive) or pH “valves” (active) ↑ pH 8. increase lubricity (↓ friction/wear) in vivo: hydrophilic surfaces 9. increase hardness enhance wear resistance 10 . enhance corrosion/degradation