Physiochemical Surface Modification & Non-fouling Surfaces

Question 1

Physiochemical Surface Modification

Answer 1

• goal is to retain the bulk physical properties of the biomaterial, while modifying the outermost layer to influence biointeractions
• should be as thin as possible while ensuring uniformity, durability, and functionality
• some possible goals: blood compatibility, cell adhesion, controlling protein adsorption, lubricity, etc
• resist layer division (delamination) by covalent bonding, intermixing (like through IPNs), or applying primer layer
• surface rearrangement at molecular scale is driven by thermodynamic minimization of “interfacial energy” (ex: fluorinated molecules blossom at the air material interface)

Question 2

Non-Specific Surface Modification Methods

Answer 2

• leave a distribution of different functional groups at the surface
• Plasma (or RFGD), which oxidizes surfaces and gases in a highly reactive environment

Question 3

Plasma (RFGD) treatment

Answer 3

• atomically and molecularly dissociated gaseous environments (contain ions, free radicals, atoms, photons, etc)
• ability to react with/polymerize molecules from the gas phase, which can then combine higher molecular weight units that precipitate onto substrate
• conformal, coat pretty much any surface, easy to prepare, and sterile
• yields ill-defined surface chemistries due to random nature of reactions (can produce highly crosslinked polymeric films)

Question 4

Specific Surface Modification Methods

Answer 4

• well-defined, reactive surface chemical groups to attach specific surface modifying species
• techniques include silanization, ion beam implantation, Langmuir-Blodgett deposition, self-assembled monolayers (SAMs), layer-by-layer and polyelectrolyte deposition, surface modifying additives, conversion coatings, and parylene coating

Question 5

Silanization

Answer 5

• densely presented on glass, silicon, alumina, titania, quartz, and other metal oxide surfaces
• bind to form self-assembled, covalently bound monolayers on hydroxylated surfaces
• silane-hydroxl bond prone to hydrolysis
• pretty much can customize which functional group the surface presents

Question 6

Ion beam implantation

Answer 6

• injects accelerated ions into the surface zone of a material
• modifies hardness, lubricity, toughness, corrosion, conductivity, and bioreactivity
• primarily used with materials with crystal lattice structure (metals, ceramics, glasses, and semi-conductors)

Question 7

Langmuir-Blodgett deposition

Answer 7

• coats a surface with one or more highly ordered layers of surfactant (amphiphilic) molecules
• molecules have a polar end and nonpolar end
• films are stabilized after by crosslinking
• uses water bath to force molecules onto surface

Question 8

Self-assembled monolayers (SAMs)

Answer 8

• requires moderate-to-strong adsorption of chemical anchoring group and van der Waals interactions of alkyl chains (9-24 carbons), producing crystalline-esque structure
• examples: n-alkyl silanes on hydroxylated substrates, amines and alcohols on platinum substrates, etc.

Question 9

Layer-by-Layer and Multilayer Polyelectrolyte Deposition

Answer 9

• alternating dip-coating of molecules with alternating charges (polyanions or polycations like hyaluronic acid and chitosan)

Question 10

Surface modifying additives

Answer 10

• added in low concentrations during bulk material fabrication
• spontaneously rise to dominate the surface, minimizing interfacial energy
• like fluoropolymers!

Question 11

Conversion coatings and Parylene coating

Answer 11

• conversion coatings modify the surface of a metal into a dense oxide-rich layer
• corrosion protection, better adhesion, sometimes lubricity (generally uses acid washes)
• parylene coating is used widely to insulate electrical components
• simultaneous evaporation, pyrolysis, deposition, and polymerization of a di-para-xylene monomer

Question 12

Non-fouling surfaces

Answer 12

• resist the adsorption of protein and/or cell adhesion
• acute/delayed versus persistent
• hydrophilic surfaces are more likely to resist protein adsorption, while hydrophobic will adsorb monolayer of tightly adsorbed proteins
• resistance at interfaces is directly related to the resistance of interfacial groups to release bound water molecules
• lots of applications (like catheters, biosensors, microfluidic devices, etc)

Question 13

Poly(ethylene glycol) (PEG)

Answer 13

• immobilized using a variety of methods, like cross-linking, surfactants, grafted brush, etc
• longer the chain, the lower the surface density needed to be non-fouling
• in SAMs, minimum of 3 EG units needed to be effective
• conformation and surface density are variables
• osmotic repulsion occurs due to highly ordered water layer created within PEG’s hydrated coils
• for large chains, entropic repulsion occurs to random polymer coils wanting to retain larger volume

Question 14

More on Non-fouling

Answer 14

• protein-coated surfaces can be considered non-fouling, as they’ll adsorb as a monolayer and resist secondary layers by retaining water
• surface packing density is critical factor
• commonly hydrophilic, electrically neutral, and have hydrogen-bond acceptor (NOT DONOR) groups
• pluronics (zwitterionic groups on backbone) and naturally occurring molecules and block non-specific protein/cell adsorption/adhesion
• kosmotropes work as well, as they order surrounding water molecules

Question 15

Thrombogenicity

Answer 15

• ability of a material to induce/promote the formation of a thromboemboli
• considered a rate parameter (low levels are tolerated as they are constantly cleared anyways)
• becomes an issue when rates clog flow paths, etc
• truly nonthrombogenic material surface does not yet exist
• a material’s thrombogenicity is characterized by level of platelet adhesion and activation, leukocyte activation, and complement activation

Question 16

Nonthrombogenic Treatments/Strategies

Answer 16

• inert materials with low thrombogenicity (unsure whether should be hydrophilic or hydrophobic)
• can coat/graft with hydrophilic hydrogels, if the chemistry fits
• PEG grafting/immobilization/surface adsorption, albumin coating/adsorption on hydrophobic surfaces
• zwitterionic groups or phospholipid mimicking
• SAMs
• heparin-like materials or surface modifying additives

Question 17

Nonthrombogenic Treatments pt 2

Answer 17

• active materials that limit thrombogenicity
• heparinization: popular, many methods, helps to inhibit thrombin and factor X with antithrombin III (acts as a catalyst)
• hirudin, curcumin, thrombomodulin (maybe expand…?)
• antiplatelet agents (platelet GPIIb/IIIa antagonist, factor X or tissue factor inhibitor)
• endothelization (ingrowth)

Question 18

Surface-Immobilized Biomolecules

Answer 18

• plenty of different chemistries and approaches for the same biomolecule to be immobilized
• maintaining bioactivity is critical (given proteins’ tendency to unfold)
• biomaterial surfaces with pendant surface hydroxyl (-OH), carbonyl (-COOH), or primary amine (-NH2) groups are advantageous in immobilizing biomaterials using “azide, alkyne, and sulfhydryl”
• for metals, metal oxides, inorganic glasses, or ceramics, can add chemically immobilized or physically adsorbed polymeric/surfactant adlayers
• use plasma discharge or ozone to modify surface composition

Question 19

Surface-Immobilizing part 2

Answer 19

• many different biologically functional molecules can be immobilized chemically/physically for other applications
• can be made cell adhesive using covalent immobilizing of ECM peptides that engage with integrin receptors
• thus, can elicit specific cell functions or enzymatic reactions
• three major methods: physical adsorption, physical entrapment, covalent attachment
• physical adsorption: van der Waals, electrostatic, affinity recognition
• physical entrapment: microcapsules, hydrogels, and physical mixtures like drug delivery
• covalent attachment: soluble polymer conjugates, conjugates on solid surfaces or within hydrogels (has support functions and major reacting groups on proteins)