1. Definition Surface Modification
Surface modification aims to tailor the surface characteristics of a material for a specific application without detrimentally affecting the bulk properties.
At present, a range of biological, physical and chemical methods are used to effect surface modifications on biomedical devices and biomaterials.

2. Methods Coating Monolayer Graft Copolimerization Synthetic polymer
Chemical initiation
Photochemical initiation
 Irradiance
Coating
Synthetic polymer
Protein
Polysaccharide
Monolayer H S
Coo-
Graft
Copolimerization
Surface modification generally falls into one of two categories:
1) modification of the existing surface, e.g., etching or chemical modification or
2) coating the surface with a different material, e.g., plasma deposition or polymer grafting.
These approaches, as showed in the picture above, can be used to affect a range of properties, including wettability, permeability, biostability and/or chemical inertness, adhesion, biocompatibility, topography, electrical characteristics and optical and frictional properties.
The figure above lists some of the common surface modification techniques used at present in biomedical engineering and the materials properties they influence.

3. Immobilization Methods
Occlusion with
covalent/crosslinking bonding
Occlusion form:
- precursors monomers
- precursors oligomers
- Polymeric chains E
Binding
Adsorption (non ionic)
Ionic bonds
Covalent bonds
Crosslinking
Occlusion +
Coatings incorporating biologically active and/or inactive molecules to generate specific, predictable and controlled responses in the biological envoirnment have been recent biomaterials research.
A wide range of biomolecules, including proteins, peptides, polysaccharides, lipids and oligonucleotides, have been immobilized on surfaces with the aim of eliciting specific, predictable and controlled biological responses.
The term "immobilized" means unable to move or stationary.  And that is exactly what an immobilized enzyme is:  an enzyme that is physically attached to a solid support over which a substrate is passed and converted to product.
When immobilizing an enzyme to a surface, it is most important to choose a method of attachment that will prevent loss of enzyme activity by not changing the chemical nature or reactive groups in the binding site of the enzyme. 
Carrier-Binding : the binding of enzymes to water-insoluble carriers.
The carrier-binding method is the oldest immobilization technique for enzymes. In this method, the amount of enzyme bound to the carrier and the activity after immobilization depend on the nature of the carrier.
According to the binding mode of the enzyme, the carrier-binding method can be further sub-classified into:
Physical Adsorption (method based on the physical adsorption of enzyme protein on the surface of water-insoluble carriers)
Ionic Binding (this method relies on the ionic binding of the enzyme protein to water-insoluble carriers containing ion-exchange residues)
Covalent Binding (this method is based on the binding of enzymes and water-insoluble carriers by covalent bonds)
Cross-Linking : intermolecular cross-linking of enzymes by bi-functional or multi-functional reagents.
Cross-linking an enzyme to itself is both expensive and insufficient, as some of the protein material will inevitably be acting mainly as a support. This will result in relatively low enzymatic activity. Generally, cross-linking is best used in conjunction with one of the other methods. It is used mostly as a means of stabilizing adsorbed enzymes and also for preventing leakage from polyacrylamide gels.
Entrapping (occlusion) : incorporating enzymes into the lattices of a semi-permeable gel or enclosing the enzymes in a semi-permeable polymer membrane. The entrapment method of immobilization is based on the localization of an enzyme within the lattice of a polymer matrix or membrane. It is done in such a way as to retain protein while allowing penetration of substrate. It can be classified into lattice and micro capsule types.
Lattice-Type entrapment involves entrapping enzymes within the interstitial spaces of a cross-linked water-insoluble polymer. Some synthetic polymers such as polyarylamide, polyvinylalcohol, etc... and natural polymer (starch) have been used to immobilize enzymes using this technique.
Microcapsule-Type entrapping involves enclosing the enzymes within semi permeable polymer membranes. The preparation of enzyme micro capsules requires extremely well-controlled conditions and the procedures for micro capsulation of enzymes can be classified as:
Interfacial Polymerization Method:  In this procedure, enzymes are enclosed in semi permeable membranes of polymers. An aqueous mixture of the enzyme and hydrophilic monomer are emulsified in a water-immiscible organic solvent. Then the same hydrophilic monomer is added to the organic solvent by stirring. Polymerization of the monomers then occurs at the interface between the aqueous and organic solvent phases in the emulsion. The result is that the enzyme in the aqueous phase is enclosed in a membrane of polymer.
Liquid Drying:  In this process, a polymer is dissolved in a water-immiscible organic solvent which has a boiling point lower than that of water. An aqueous solution of enzyme is dispersed in the organic phase to form a first emulsion of water-in-oil type. The first emulsion containing aqueous micro droplets is then dispersed in an aqueous phase containing protective colloidal substances such as gelatin, and surfactants, and a secondary emulsion is prepared. The organic solvent in then removed by warming in vacuum. A polymer membrane is thus produced to give enzyme micro capsules.
Phase Separation:  One purification method for polymers involves dissolving the polymer in an organic solvent and re-precipitating it.  This is accomplished by adding another organic solvent which is miscible with the first, but which does not dissolve the polymer.

4. Methods of surface techniques used for biomaterials 1
Modification
Properties
Plasma Techniques Polymerization
Organic and inorganic coatings with tailored physicochemical properties.
Barrier coatings (thermal and chemical). Control of chemical functionality, cell and protein adhesion.
Sputtering and etching
Chemical and physical deposition and etching.
Surface cleaning, introduction of topographical features and chemical functionality.
Spraying
Deposition of metals and inorganic coatings.
Enhanced corrosion and ablation resistence. Improve biocompatibility.
Grafting copolymerization
Creation of radicals to iniciate polymerization.
Polymer grafting for enhanced biocompatibility and nonfouling.
UV and Gamma and Laser irradiation
Chemical funcionalization and etching.
Polymer grafting, enhanced biocompatibility, introdution of topographical features.
Biomolecule attachment
Chemical and biological.
Biomimetric surfaces, introdution of specific biological function and activity.
Molecular imprinting
Chemical and topographical.
Cell and protein selectivity and improved biological functionality.
Self assembly
Introduce functionality, nonfouling and biomimetric properties.
The table above lists some of the common surface modification techniques used at present in biomedical engineering and the materials properties they influence.
1 Adapted from: Wnek, G.E., Bowlin, G.L., Encyclopedia of Biomaterials and Biomedical Engineering, Marcel Dekker, Inc., USA, vol. 2, 2004

5. Improve blood compatibility
Modifications
Surface
Modification
Improve blood compatibility
Protect the
body from
the device
Modify the
appearance
device from
the body
Alter the
protein adsortion
characteristics
Reduce
(or increase)
tissue adhesion
Add biologically
active substances to
the surface layer
Increase or decrease
wettability of the surface
Some examples of surface-modified biomaterials are:
To modify blood compatibility:
- Octadecyl group attachement to surface (albumin affinity)
- Silicone-containing block copolymer additive
- Plasma fluoropolymer deposition
- Plasma siloxane polymer deposition
- Radiation-grafted hydrogels
- Chemically modified polystyrene for heparine-like activity
To influence Cell Adhesion and Growth:
- Oxidized polystyrene surface
- Ammonia plasma-treated surface
- Plasma -deposited acetone or methanol film
- Plasma fluoropolymer deposition (reduce endothelial adhesion to IOLs)
To Control Protein Adsorption:
- Surface with immobilized poly(ethylene glycol) (reduce adsortion)
- Treated ELISA dish surface (enhance adsorption strength)
- Affinity chromatography particulates (reduce adsorption or enhance specific adsorption)
- Surface-cross-linked contact lens (reduce adsorption)
To improve lubricity:
- Plasma treatment
- Interpenetrating polymeric networks
To improve wear resistance and corrosion resistance:
- Ion implantation
- Diamond deposition
- Anodization
To alter transport properties:
- Plasma depositions (methane, fluoropolymer, siloxane)
To modify electrical characteristics
- Plasma deposition (insulation layer)
- Solvent coatings (insulator or conductor)
- Parylene (insulation layer)

6. Membranes Characterization
Superficial – contact angle determination
Zeta Potential
Diffusion coefficients of ions and other compounds
Water sorption capacity
Scanning electron microscopy
Any surface modification should be physically, chemically and biologically characterized. A range of highly sensitive surface analytical methods exist, like:
Superficial – contact angle determination
Zeta Potential
Diffusion coefficients of ions and other compounds
Water sorption capacity
Scanning electron microscopy

7. Characterization of a solid surface
Contact angle
Angle which encloses the tangent line on the drop shape from the three-phase point to the base line on the solid surface
LV
liquid
air
SL
SV 
solid
Contact angle ,θ , is a quantitative measure of the wetting of a solid by a liquid. It is defined geometrically as the angle formed by a liquid at the three phase boundary where a liquid, gas and solid intersect.
Most often the concept is illustrated with a small liquid droplet resting on a flat horizontal solid surface. The shape of the droplet is determined by the Young-Laplace equation.
Contact angle is measured using a contact angle goniometer. A goniometer is an instrument that either measures angles or allows an object to be rotated to a precise angular position.
As a definition of contact angle,it is not always the case of liquid/vapour interface, rather, we can use interface between fluids.Contact angle is equally applicable to interface of two liquid or two vapours.
Balance between adhesion and cohesion forces

8. Biomaterials Contact Angle
Low values of contact angle indicate that the liquid spreads, or wets well
High values indicate poor wetting once the cohesive forces increases
Contact angle greater than 90º indicates non- wetting
As demonstrated in the pictures above, low values of cotact angle indicate that the liquid spreads, or wets well , while high values indicate poor wetting. If the angle θ is less than 90 the liquid is said to wet the solid. If it is greater than 90 it is said to be non-wetting. A zero contact angle represents complete wetting.

9. Contact angle vs. Surface
Biomaterials
Contact angle vs. Surface
 liquid
vapour
LV
SL
SV
SV = interfacial tension of the solid/vapour interfaces
 SL = interfacial tension of the solid/liquid interfaces
 LV = interfacial tension of the liquid/vapour interfaces
In 1805 YOUNG had already formulated a relationship between the interfacial tensions at a point on a 3-phase contact line.
Three interfacial free energies have to be assumed, if a liquid is in contact with a solid surface as indicated above:
γSV = interfacial tension of the solid/vapour interfaces
γSL = interfacial tension of the solid/liquid interfaces
γLV = interfacial tension of the liquid/vapour interfaces
During equilibrium: γ SV = γ LS + γ LV cos θ (young’s equation)
The Young's Equation defines the balances of forces caused by a wet drop on a dry surface.
SV = LS +  LV cos  (1)

10. Contact angle determination (Young-Dupré's Equation)
Biomaterials
Contact angle determination
Young's Equation:
LV . cos  = gSV – gSL (1)
Adhesion work:
WA = SV + LV - SL (2)
WA = LV (1 + cos ) (3)
If the drop will be removed from the padding, energy is needed to form equal area of liquid and solid surface and energy will be obtained, which was stored in the liquid/solid interface. Therefore, according to DUPRÉ, the generation of equal areas of solid and liquid surfaces and the stored interfacial energy is given by the Adhesion work equation:
WA = SV + LV - SL
Comparing this equation with young’s equation, gives the following equation, which is known as Young-Dupré's Equation:
WA = LV (1 + cos )
From this equation it could be seen that work has always to be done, if a wetting procedure is canceled. We also see that the contact angle can be predeterminated and could be foresen, if the work of adhesion, W, and the surface tension of the liquid are known.
(Young-Dupré's Equation)

11. Wettability Biomaterials Ability of liquids to spread on a surface
Can be measured by contact angle determination
Measurements of surface tension yield data which directly reflect thermodynamic characteristics of the liquid tested. While measurement of contact angles yield data which reflect the thermodynamics of a liquid/solid interaction. If you wish to characterize the wetting behavior of a particular liquid/solid pair you only need to report the contact angle. It is possible to characterize the wettability of a solid in a more general way.
The solid is tested against a series of liquids and contact angles are measured. Calculations based on these measurements produce a parameter(critical surface tension, surface free energy,etc) which quantifies a characteristic of the solid which mediates wetting.

12. The energy of a solid surface is higher then inside it
Biomaterials
Surface Energy
The energy of a solid surface is higher then inside it
On the inside all atoms are equally attracted by each other
Surface energy quantifies the disruption of chemical bonds that occurs when a surface is created. In the physics of solids, the energy of a solid surface is higher then inside it. On the inside all atoms are equally attracted by each other. On the surface the energy is higher because atoms are not equally attracted in every directions.
The surface free energy of a solid is sometimes also referred as the "surface tension" of the solid substrate. The surface tensions of solid-vapour interfaces and solid-liquid interfaces are important parameters in many areas of applied science and technology. These interfacial tensions are responsible for the behaviour and properties of commonly used materials such as paints, adhesives, detergents and lubricant.
On the surface the energy is higher because atoms are not equally attracted in every directions

13. Energy per area value increase
Biomaterials
Surface Energy
Energy per area value increase
Compensation
Atoms stablish bonds between each other on their surrounds, reducing the energy value
In 1805, Thomas Young first described that the surface energy is the interaction between the forces of cohesion and the forces of adhesion which determines whether the spreading of a liquid over a surface occurs.
So, surface free energy is defined as the work required to increase the area of a substance by one unit area.
If the surface is hydrophobic then the contact angle of a drop of water will be larger. Hydrophilicity is indicated by smaller contact angles and higher surface energy. Water has high surface energy by nature; it's polar and forms hydrogen bonds.

14. Bibliography Books Web Sites Figures References
Buddy D. Ratner, Allan S. Hoffman, Frederick J. Schoen, Jack E. Lemons, "Biomaterials Science: An introduction to materials in medicine”, Academic Press, 1996.
Wnek, G.E., Bowlin, G.L., “Encyclopedia of Biomaterials and Biomedical Engineering”, Marcel Dekker, Inc., USA, 2004
Web Sites
Figures References