Chemical Bonding

(Surface modification 2)

Methods x7

1. Chemical reaction

2. Radiation grafting and photografting

3. RFGD Plasma Deposition

4. Silanization

5. Ion beam implantation

6. Self-assembled monolayers

7. Coating

1. Chemical reaction

x3

1. Specific (high yield, few side reactions) v.s.

    Nonspecific (many function groups)

2. Attach organic, biological molecules

    e.g. protein resistance, biorecognition by antibodies, immunoevasion (evade from immune system)

3. Form covalent bond

    strong bond and stable film

    couple polymer with a linker

    need -OH, -NH2

    complicated and long

2. Radiation Grafting and Photografting

Process x2

charateristics of formed layers x3

radiation breaks bonds

monomer reacts with free radicals and propagates to other monomers

thick

well bonded to material

can use many surface chemistries

3. RFGD Plasma Deposition

use what? x2

advantage x7

disadvantage x4

low pressure ionized gas environment

plasma introduce organic groups to bind biomolecules

conformal

free of voids

placed on any solid

good adhesion

low leachables

easily prepare

sterile

ill-defined chemistry

monomer scramble

expensive

uniform reaction in long, narrow pores is hard

 4. Silanization

use

process x2

advantage x3

disadvantage x1

modify hydroxylated (-OH) surfaces

(add Si)

obtain monolayer or 3D polymerized network

catalyzed by water

simple reaction

stable (covalent)

many functionalities for reaction

hydrolysis

5. Ion Beam Implantation

process

function x5

ions enter surface

hardness, wear, lubricity, corrosion, bioreaction

6. Self-assembled monolayers (SAMs)

process

advantage x3

disadvantage x2

spontaneously form crystal coating

Top: functional head

Middle: van der Waals/hydrophobic interaction of alkyl chains

Bottom: exothermic adsorption of an anchoring group to surface

easy

chemical stable

can change outermost group

poor in vitro(outside body)/in vivo(inside body) stability

need metal surface

Adsorption

(Surface modification 3)

characteristics x4

example

non-colvalent bonds

hydrophobic

electrostatic

multilayer polyelectrolyte films

biomimetic peptide coating

• cells attach to material by Interfacial biomaterial (IFBM)

Topography affects cells in 3 ways

1. adhesion -- osteoblasts favor rough & fibroblasts favor smooth
2. interlocking reduces motion
3. porosity

Bulk properties (no interface)

x4

1. chemical composition
2. microstructure: atom, crystalinity
3. leachables, additives
4. mechanics, durability, functionality

surface properties (with interface)

x5

1. chemical reactivity
2. smoothness
3. surface tention & energy
4. surface charge
5. biological response (e.g. surface protein direct cell behavior)

Regulate cell behaviors at biomaterial-tissue interface

x4

1. prevent nonspecific protein absorption
2. retain protein activity on material
3. protein surface distribution
4. immobilize protein

soluble protein

(1) 位置

(2) 例子x2

(3) shape

(4) structure

(5) hydrophilic/hydrophobic

(6)与biomaterial和cell的interaction

(1)

blood plasma, peritoneal （腹膜） exudate （分泌物）

(2)

fibrinogen, albumin

(3)

spherical/globular (except fibrinogen)

(4)

amino acid structure

(overall anionic or cationic charge)

(5)

内——hydrophobic

外——hydrophilic

(6)

protein absorbs to surface very fast;

cells bound to protein surface, not bulk material

fibrinogen

(1) synthesized in

(2) function

liver

1. convert to fibrin by thrombin
2. form clot
3. cover wound with platelets

albumin

特色 x3

功能 x2

amino acid

no carbonhydrate

60% plasma protein

(1) maintain colloid （胶体） osmotic pressure

(2) carry low H2O woluble molecules

      (e.g. hormones, bile salts, drugs)

Insoluble protein

特色 x2

例子 x1

• can't diffuse to implant surface
• secreted by cells

collagen

difference between adsorption (x2)

and absorption (x2)

• atoms, molecules, or ions adhere to surface
• localize

• permeation of a fluid
• involves whole volume

Protein race for surface to form monolayer

what will happen? x4

adsorption v.s. protein concentration plot

1. proteins differ in surface activity
2. Vroman Effect (high mobile proteins arrive first; later replaced by less mobile but high affinity proteins)
3. conformation change
4. desorption/re-adsorption

 [image]

影响protein surface activity的因素

x3

• hydration of sorbent （吸附剂） and protein
• Coulombc interaction (redistribution of charge)
• during adsorption, protein structure rearrange

driving force for adsorption

x3

• protein bulk concentration
• intrinsic surface activity
• affinity

surface properties governing protein adsorption

(1) hydrophobicity   x3

(2) surface and protein charge

(3) physical   x3

• more hydrophobic, more adsorption
• contact angle
• polymer > metal & ceramics

 [image]

• steric （原子空间排列） hindrance
• big, hydrophilic polymer has small adsorption
• more rough, more adsorption (trapping)

thermodynamics of adsorption

x3

• Gibbs free energy ΔG = ΔH - TΔS < 0

• ΔG = work (protein-solid work of adsorption)

• ΔG = g(ps) - g(pl) - g(sl)

g - interfacial tensions (imbalance of force between phases, energy required to increase surface area of interface)

p - protein

s - solid

l - liquid

protein denaturation

特性 x3

• disruption/unfolding of secondary/tertiary structure
• reversible/irreversible
• denatured protein absorbed to surface

[image]

protein absorb

定义

过程

• remove from surface, back to solution

• hydrophobic residues exposed to H2O, aggregate or precipitate

influence of surface protein denaturation

x3

cellular response

biocompatibility

immunogenicity

(absorbed) surface-protein interaction mediates celluar response

例子 x3

governed by x4

adhesion, proliferation, differentiation

1. amino acid side groups (polarity, charge)
2. portein archetecture (hydrophobic inside, steric conformation)
3. thermodynamics
4. protein concentration （越密，越多cell bind，surface protein远比bulk phase时多）

cell adhesion to surface

例子

influenced by   x4

adherent cells

• 负电（anion) cell membrane
• surface charge density & distribution
• chemistry
• porosity

• strong, non-specific (only growth)
• weak
• strong, specific (growth and function)

platelets

特点 x3

adhesion proteins x4

how it works

enucleated

budding off megakaryocytes (bone marrow)

source of growth factor

fibrinogen, fibronectin, vitronectin, von Willibrand factor

absorbed protein localize them

Implant Failure due to surface

Examples x3

Joints: imporper tissue integration

Delivery: membrane clog

Stents: improper signal

Goal of surface modification

x6

1. protein adsorption (biosensor)
2. cell adhesion & growth (hip implant)
3. blood compatibility (stent)
4. prevent fibrous capsule formation (breast implant)
5. increase lubricity, wear/corrosion resistance
6. change electrical characteristics

Surface modification

category   x4

1. metallization
2. chemical bonding (covalent)
3. adsorption (weak, non-covalent)
4. topography 地形 (uniform, gradient, patterned)

Metalization

1. metal coating
2. thin surface
3. delamination （分层，起皮） resistance

        covalent bonded

        加primer layer

        加function group for intermolecular adhesion