Surface

modica.ons for enhancing the blood-compa.bility

Physical Properties of Biomaterials 2011-2012 K.U. Leuven M.Sc. in Molecular and Cellular Biophysics Asterios Ntais | asterios.ntais@gmail.com

Introduc)on

Several biomaterials are used in biomedical applications in order to increase the quality of life and lifes expectancy. A biomaterial inside the human body must be continuously under the examination of blood-biomaterial interactions in order to avoid any lethal and undesired reaction. Blood Functions and Properties Biomaterials interaction with blood components Surface Properties and Modi9ication Strategies Modi9ication Methods

Blood Func.on and Proper.es

Surface modiJications for enhancing the blood-compatibility
Physical Properties of Biomaterials

Blood Func)on and Proper)es

43%

delivers several vital and functional substances to the cells via the circulation system delivers O2 to tissues and organs, in order to be used for combustions receives the useless and harmful products of metabolism and delivers them to the excretory organs heat transfer

55% 1% 1% Plasma White Cells Red Cells Platelets

Blood Func)on and Proper)es

contributes to the immunological system the hemostatic mechanism is designed to arrest bleeding from injured blood vessels when artiJicial surfaces are placed in contact with blood the same process may cause undesired reactions between:

surface platelets - coagulation proteins

cause harmful effects for the living organisms e.g. formation of thrombus

Blood Func)on and Proper)es

blood is a viscous, inhomogeneous and non-Newtonian Jluid a suspension of cellular components [liquid state] main properties:

opacity (different refractive index between components) red tint (RBC hemoglobin) viscosity is 310-3 to 310-4 Pascal-seconds at 37oC slightly alkaline with pH from 7.35 to 7.44 speciJic gravity is 1.06 gr/cm3 HCT is determined as the % content of blood cellular components

Biomaterials interac.on with blood components

Surface modiJications for enhancing the blood-compatibility
Physical Properties of Biomaterials

Biomaterials interac)on with blood components

complex and dynamic phenomena and the examination of b-b interactions indicates that relevant features are: protein adsorption platelet reactions intrinsic coagulation ECM proteins Jibrinolytic activity 9ibrinogen erythrocytes, leucocytes and complement albumin activation -globulin plasma and ECM proteins adsorption play a crucial role in balancing thrombosis and hemostasis

Protein Adsorp)on

amino acids side chains (polar/non-polar, charge) contribute to the interactions the protein molecules are the Jirst substances that are absorbed this process contributes to the surface activity a bio-layer of H2O and proteins is formed cells from surrounding tissues migrate onto the surface

Protein Adsorp)on

Vroman effect: proteins with high concentration in the blood, Jirstly adsorbed on a surface, but due to the weak adhesion replaced by others proteins expose their hydrophobic regions to the surface in order to: increase the area of contact to minimize the energy interaction with the surface Jinally, proteins tend to cover the whole area of the surface

i. ii.

Main Factors
1. the properties of protein molecules
conJiguration, electrostatic charge distribution, intermolecular bonds

2. the surface properties

structure, composition, contaminants, additives, wettability, hydrophobicity/hydrophilicity ratio, functional groups, receptor sites, potential, density, crystallinity, porosity, roughness, texture, polarity

3. the solution characteristics

pH and salt concentration

Protein Adsorp)on
the main interactions are: hydrogen bonding - Van der Waals electrostatic thermodynamic viewpoint:: G=H-TS <0 G<0 S>0 the process must be sufJiciently exothermic or to be accompanied by a large increase of entropy

Adverse eects

hemolysis: destruction of erythrocytes; impedes the circulatory system ability to transfer O2 to the tissues thrombus formation: affects the Jluidity of blood and causes hemostasis changes in clotting factors and white blood cell activation

ISO 10993-4:2000: Selection of tests for interactions with blood

Surface Proper.es and Modica.on Strategies

Surface modiJications for enhancing the blood-compatibility
Physical Properties of Biomaterials

Surface Proper)es and Modica)on Strategies

surface properties are as important as the bulk properties and often deJine each other surface characteristics are responsible for the control of interactions between the material and the external environment biological responses to biomaterials are related with the surface chemistry and structure, topography and energy

in order to increase the blood-compatibility, surface modiJications techniques are necessary and should retain the physicochemical properties to inJluence bio-interactions

Surface Proper)es and Modica)on Strategies

surface modi9ication techniques are trying to optimize:

protein adsorption, generation of thrombin and its function (blood coagulation platelet adhesion cellular behavior in the surface)
i.

main modi9ication strategies: chemical or physical alternations to atoms and/or molecules in the existing surface coating over the existing surface with a material, which have a new composition

ii.

Modica.on Methods
Surface modiJications for enhancing the blood-compatibility
Physical Properties of Biomaterials

Hydrogels
are hydrophilic polymeric structures contain covalent and hydrogen bonds physical cross-links governed by Van der Waals interactions bind in their volume large amount of H2O degree of Jlexibility similar to human tissues low interfacial tension increase hydrophilicity dont support cell adhesion and thrombus formation

Self-Assembled Monolayer (SAMs)

organized organic Jilms amphiphilic molecules chemisorption of a chemical substance in a solid substrate driving force to Jill the surface

molecular level control and easy formation change a hydrophobic surface to hydrophilic

changes to the tail groups dont affect the rest molecule

Surface Modifying Addi)ves (SMA)

small molecular weight and low concentration compared to bulk properties the interfacial energy difference lead the additives to concentrate in the surface molecular mobility determines the rate that additives reach the outer surface SMA blended polymers or SMA coated surfaces, increase the blood compatibility and decrease the risk of thrombogenicity

Langmuir BlodgeG Deposi)on

Amphiphilic molecules are spread on H2O and compressed by a barrier to compose a monolayer of organic material. Then they transferred to a vertical plate at constant surface pressure. Finally, highly ordered and active molecules cover a surface.

LB Jilm contains one or more monolayers is formed by molecules with hydrophobic tails and hydrophilic heads the head-water interactions is more favorable than the air- water reduction of the surface energy high degree of order (physical adhesion)

Heparin-mime)c materials

heparin is an anticoagulant and minimize thrombus formation on artiJicial surfaces modiJied synthetic polymers with similar properties with heparin however, heparin allows the platelets adhesion to foreign surface and may cause hematoma, hemorrhage and other complications immobilize chemically anticoagulant to increase blood compatibility of a polymer grafting sulphonate and/or amino acid sulphonamide groups on insoluble polystyrene

Plasma Treatments

plasma is the 4th state of matter similarities with ionized gas consists of: e-, ions, photons, free radicals and neutral particles is created by the application of energy: RF, microwaves, laser or e- from a hot Jilament to a gas source in a vacuum chamber behaves collectively no speciJic shape and volume

Plasma Treatments

when an atom or a molecule gains enough energy, ionization occurs inside the plasma: particles motion = local accumulations | (+) or (-) large scale el. Jields affect the motion of charged particles far enough compared to their size elastic and inelastic collisions momentum and charge transfer cause particles current that abut to the surface

Plasma Treatments

removes atoms or chem. groups from the surface by bond Jissions gaseous, metallic, and laser-based sources Jlow of free radicals and ions from plasma to the biomaterial ionization, fragmentation and excitation treatments are reliable, low-cost and applicable to different geometries cause changes in chemical, electrical, biological, optical, and mechanical properties

Plasma spuGering and etching

surface cleaning techniques via chemical reactions inert gases such as neon and argon are used 1 to several kV are applied and argon plasma is generated the energy is not very high, the argon ions cannot go very deeply into the substrate a big portion of their energy is transferred to the surface atoms via elastic and inelastic collisions some surface atoms escape into the vacuum chamber

Plasma spuGering and etching

the underlying layers will be exposed and etched after enough sputtering time, surface will be cleaned off two possible and competitive reactions:
1.

modi9ication: the properties of the polymeric biomaterial will alter because of ion beam interactions and plasma polymerization degradation: etching will take place in the surface

2.

Plasma spuGering and etching

Plasma etching:

after enough time of exposure to plasma, the exposed layers of the polymers are etched off the rate of weight loss is dependent on the nature of polymer and the energy of plasma happens mainly in the top layer the modiJied polymers have the same physicochemical properties as the original ones [composition, structure, degree of polymerization]

Plasma implanta)on of polymers

polymeric materials are hydrophobic the conversion to hydrophilic improves adhesion strength and biocompatibility a polymer exposed to plasma, cross-linked chains can be formed hydrogen is abstracted from polymer chains to create radicals radicals recombine with simple radicals created by gas to form oxygen functionalities ion implantation and the formation of oxygen functionalities increase the hydrophilic properties

Plasma deposi)on

thin plasma is produced due to the action of plasma easily prepared pinhole-free, dense, cross-linked act as an efJicient barrier when constituents of plasma are activated, polymerize by addition reaction accumulation of a polymeric coating with controlled thickness

Conclusions

blood-biomaterials are an extremely complex phenomenon due to the number of parameters. the physiological response of blood and its mechanisms are well deJined when a biomaterial enter the the human body several techniques from Materials Science in combination with biology-oriented methods try to increase the levels of blood-compatibility individual usage per case