Material Properties

Question 1

Bulk properties

Answer 1

Throughout the material sample

Question 2

Surface properties

Answer 2

Top few layers of material samples.

• Biomaterials “show” to the world (and the biological environment) only surfaces.
• The atoms and molecules that reside at the surface have a special organization and reactivity.
• An important question in biocompatibility is how the device or material “transduces” (through the surface) its structural makeup to direct or influence the response of proteins, cells, and the organism to that material.

Question 3

Methods to evaluate Bulk properties of a material

Answer 3

Mechanical, Thermal, Optical

Question 4

Methods to evaluate Surface properties of a material

Answer 4

Wettability, Chemistry, Morphology

Question 5

BULK: Mechanical Properties

Answer 5

The mechanical properties of a material refer to the characteristic values of a material under various mechanical loading conditions.

• Stress and strain are two mechanical variables that are commonly referred to for a material, but they are not properties of the material.
• Only the stresses that cause certain structural changes, such as yielding or breaking, etc. will be regarded as properties.
• Of interest are elastic properties (elastic limit), Yield strength (yield point), Ultimate tensile strenght and breakpoint.

Question 6

BULK: Thermal Properties

Answer 6

• Thermal conductivity becomes a significant consideration if an implanted material contributes to an unnatural flow of heat through the surrounding tissue.
• For example, metal rods selected for their combination of stiffness, strength, fracture toughness, and biocompatibility can promote heat loss and cause the patient to feel colder than normal.
• Heat capacity is the materials ability to absorb heat.
• Thermal conductivity is the ability of a material to transfer heat.
• Thermal expansion is a (nominal) strain that occurs when the temperature of a material is changed.

Question 7

BULK: Optical Properties

Answer 7

In the context of biomaterials, the most significant bulk optical properties are color, refractive index, and transparency; all three are important in the selection of materials for intraocular lenses or fluids.

Question 8

SURFACE: Wettability

Answer 8

• Implanted biomaterials will come into contact with H20 and participate in corresponding biological interaction through the influence of adsorbed water on the amount and conformation changes of adsorbed proteins.
• Wettability refers to chemical reactivity of surface layer, implying a ‘race’ between water molecules and proteins to adsorb to the surface. Particularly as hydrophobic surfaces are considered to be more protein adsorbent.
• Adsorbed proteins then further influence platelet adhesion/activation, blood coagulation and adhesion of cells.
• Wettability property particularly used to predict the performance of vascular grafts and the adhesion of cells to surfaces.
• CONTACT ANGLE can be explained as a balance between the force with which the molecules of the drop liquid are being attracted to each other (a cohesive force) and the attraction of the liquid molecules for the surface (an adhesive force), with an equillibrium established between them.
• The force balance manifested through the CONTACT ANGLE of the drop with the surface can be used to quantitatively characterise the energy of the surface.

Question 9

Advantages and disadvantages of contact angle measurements

Answer 9

• Contact angle methods can be inexpensive, and, with some practice, easy to perform.
• A contact angle goniometer (a telescope to observe the drop that is equipped with a protractor eyepiece) is the least expensive method for contact angle measurement.
• A number of companies now offer video systems that compute the contact angle and other surface energy parameters from digital image analysis of the liquid drop profile.
• Contact angle measurements provide a “first-line” characterisation of materials and can be performed in any laboratory.
• Contact angle measurements provide a unique insight into how the surface will interact with the external world.

DISADVANTAGES

• The measurement is operator dependent
• Surface roughness influences the results
• Surface heterogeneity influences the results
• The liquids used are easily contaminated
• Liquid evaporation and temperature changes can impact measurement.
• The liquids used can absorb into the surface, leading to swelling.
• The liquids used can dissolve the surface.

Due to extensive disadvantages, should be followed by more sophisticated techniques to characterise material properties.

Question 10

SURFACE: Chemistry (ESCA [aka. XPS])

Answer 10

• Electron spectroscopy for chemical analysis (ESCA) provides a comprehensive qualitative and quantitative overview of a surface that would be challenging to obtain by other means.
• In contrast to the contact angle technique, ESCA requires complex, expensive apparatus and demands considerable training to perform the measurements.
• ESCA is based on the photoelectric effect, properly described by Einstein in 1905.
• X-rays are focused upon a specimen.
• The interaction of the X-rays with the atoms in the specimen causes the emission of core level (inner shell) electrons.
• The energy of these electrons is measured and their values provide information about the nature and environment of the atom or atoms from which they originated.

Question 11

Advantages and Disadvantages of ESCA

Answer 11

• The advantages include high information content, surface localization of the measurement (outermost 8–10nm), speed of analysis, low damage potential, and the ability to analyze most samples with no special specimen preparation (biomedical devices (or parts of devices) can often be inserted, as fabricated and sterilized, directly in the analysis chamber for study).
• The disadvantages include the need for vacuum compatibility (i.e., no outgassing of volatile components), the vacuum environment and its impact on the specimen (particularly for hydrated specimens), the possibility of sample damage by X-rays if long analysis times are used, the need for experienced operators, and the cost associated with this complex instrumentation.
• Vacuum limitations can be sidestepped by using an ESCA system with a cryogenic sample stage. At liquid nitrogen temperatures, samples with volatile components, or even wet, hydrated samples, can be analyzed.

Question 12

SURFACE: Morphology (SEM)

Answer 12

• Surface offers morphological cues dependent on fibre alignment, porosity and roughness, to direct cell migration and influence cell adhesion, differentiation and proliferation.
• Scanning electron microscopy (SEM) images of surfaces have great resolution and depth of field, with a three-dimensional quality that offers a visual perspective familiar to most users.
• SEM functions by focusing and rastering a relatively high-energy electron beam (typically, 5–100 keV) on a specimen that is under vacuum.
• Low-energy secondary electrons (1–20eV) are emitted from each spot where the focused electron beam impacts.
• The intensity of the secondary electron emission is a function of the atomic composition of the sample and the geometry of the features under observation.
• The image of the surface is spatially reconstructed on a phosphor screen (or CCD detector) from the intensity of the secondary electron emission at each point.

Question 13

Advantages and Disadvantages of SEM

Answer 13

• Disadvantageously, nonconductive (insulating) materials observed in the SEM are typically coated with a thin, electrically grounded layer of metal to minimize negative charge accumulation from the electron beam. Therefore, the surface of the metal coating is, in effect, what is being monitored –> specimen surface chemistry no longer influences secondary electron emission. Yet, the development of low-voltage SEM does study the surface chemistry (and geometry) of nonconductors.
• Advantageously, an important corroborative method to use in conjunction with other surface analysis methods. Surface roughness and texture can have a profound influence on data from ESCA, SIMS, and con- tact angle determinations. Therefore, SEM provides important information in the interpretation of data from these methods.

Question 14

Surface interaction: Blood-Material Interactions

Answer 14

• The hemostatic mechanism designed to arrest bleeding from injured blood vessels may produce adverse consequences when artificial surfaces are placed in contact with blood.
• These events involve a complex set of interdependent reactions between:
  (1) the surface;
  (2) platelets; and
  (3) coagulation proteins, resulting in the formation of a clot or thrombus, which may subsequently undergo removal by fibrinolysis.
• The process is localized at the surface by opposing activation and inhibition systems, which combine to maintain the fluidity of blood in the circulation.

PLATELETS:

• Platelets adhere to artificial surfaces and injured blood vessels.
• Mediated by adsorbed proteins. involves the interaction of platelet glycoprotein Ib (GP Ib) and connective tissue elements, which become exposed (e.g., collagen) and require plasma von Willebrand factor (vWF) as an essential cofactor.
• When an artificial material comes in contact with blood, the surface of the material is coated with an adsorbed layer of blood-plasma proteins within a matter of seconds.
• This process is initially kinetically driven, which results in the surface being first coated with the fastest diffusing proteins, such as albumin.
• Platelets remaining adherent to the protein-coated surface result in the growth of thrombus on the material surface, leading to the reduction or possible complete block- age of blood flow, or the possible loss of function of the implanted prosthesis, such as has occurred with artificial heart valves and ventricular assist devices.

COAGULATION:

• Initiation of clotting occurs either intrinsically by surface-mediated reactions that occur within a blood vessel, or extrinsically due to blood contacting tissue external to the vasculature due to a disrupted blood vessel wall through factors derived from tissues (i.e., tissue factor).
• Intrinsic contact activation refers to reactions following the adsorption of contact factors to a material surface.
• Contact activation of the blood coagulation cascade.

Question 15

Non-fouling surfaces

Answer 15

• Surfaces that resist the adsorption of proteins and/or the adhesion of cells.
• Most common non-fouling material is PEG (poly(ethylene glycol)).
• Important as thrombus formation against artificial surfaces by both platelet adhesion and contact activation is mediated by adsorbed proteins.

Question 16

How a materials’ surface can be modified to alter biological interactions (platelet adhesion and contact activation).

Answer 16

• Resistance to protein adsorption at biomaterial interface is directly related to the interfacial groups in response to their bound waters of hydration.
• —> surfaces that like water (hydrophillic) are typically non-fouling.
• Surface Modifications:
• Surface coatings that are strongly resistant to protein adsorption. (However, while demonstrated to be highly effective in vitro, these surface chemistries have not been shown to be fully effective in eliminating protein adsorption and subsequent thrombus formation in vivo).
• —> further research and development into surface modifications:
• Surface functionalization with bioactive molecules that inhibit thrombus formation.
  (1) Heparin is a natural polysaccha- ride, which, in combination with antithrombin III (ATIII), strongly binds and deactivates thrombin. Heparin–ATIII complexes can also inhibit other blood coagulation factors including XIa, Xa, and IXa.
  (2) Polymer coatings that release nitric oxide (NO), which are strong inhibitors of thrombin formation. One of the inherent limitations of this approach, however, is that once the NO release is diminished, prevention of thrombus formation is lost, thus potentially limiting this approach to short-term blood-contact applications.
  (3) Coatings designed to bind to plasminogen, which upon activation by circulating plasminogen-activating factor may result in the rapid breakdown of thrombus if it begins to form on the material surface.
• Coating of surfaces with endothelial cells in attempts to provide surfaces that resemble that of natural blood vessels.
  (1) This approach has proven to be extremely difficult to achieve. As a biological cell, endothelial cells used for surface coatings must be of autologous origin to prevent immunological reactions against these cells.
  (2) Another approach, in situ endothelialization, requires functionalizing the surface with bioactive molecules designed to stimulate the migration and proliferation of endothelial cells from the adjacent vasculature, or to capture endothelial progenitor cells from the circulation and stimulate their maturation to form a firmly attached endothelial cell layer to completely cover the material surface.
• Unsuccessful thus far.
• The solution to this problem may require the implementation of more complex multifaceted in vitro test methods combined with in vitro test-method standardization.
• Surface modification is particularly important for materials that have desired bulk properties, as they made need to have their surface altered to be protein resistant, resistant to cell adhesion or offer specific cell adherence.