Biomedical Engineering Reference
In-Depth Information
layer in which patterns can be created by selectively exposing certain areas to light. The
light degrades the exposed portions of photoresist, leaving a bare biomaterial surface. Pro-
teins or molecules can then be selectively attached to these exposed areas. The remaining
photoresist is then removed to obtain a biomaterial surface that has protein or molecular
patterning. This type of photopatterning of a protein results in a substrate with specific
areas for enhanced cell attachment. Using this technique, researchers were able to see that
cells responded differently to being cultured on small, round-shaped areas rather than
larger, square areas. When cultured in medium that supported fat cell differentiation, only
the cells at a high density on the small circular areas became fat cells, while those cells
allowed to spread out on the larger square areas became bone cells. Restricting or enhanc-
ing cell attachment can thus govern cell differentiation.
Instead of modifying the exposed areas with proteins, the material that is exposed can be
deeply etched, leading to a pattern of grooves or pits. The directed activity of cells by a
groove in a biomaterial is known as contact guidance. When cells encounter grooves or pits,
they change their shape and align or elongate along topographic features. This is a tech-
nique that can lead to ordered alignment of cells on a surface, which is necessary if the goal
is to mimic the normal alignment of cells in muscle, blood vessels, and nerves. The distor-
tion of the cytoskeleton within the cell imparts biological messages to the cell nucleus, lead-
ing to changes in gene expression.
There are many methods for modifying the surface of biomaterials, and new technology
continues to be developed. It has been observed that the topography or roughness must be
on a biologically relevant scale (1-10
m) to affect cell growth and attachment. Other meth-
ods for modifying surface topography that provide this type of resolution include surface
roughening by laser ablation or wet etching with a corrosive solvent, or molding or casting
a biomaterial in melt form into a rigid mold. Hot embossing or imprint lithography forms a
relief replica of a mold by pressing it into a thermoplastic material. Microcontact printing is
the most often used method to create chemical patterns for cell substrates. An elastomeric
stamp is used to place a biologically active compound, such as a protein, onto a substrate
through contact transfer. These techniques are not only for polymeric substrates. Metals
can be roughened as well through sandblasting with ceramic particles or chemical etching
by being placed in an alkaline or an acidic solution that erodes its surface, leaving pits of
specific diameter and shape.
Since many metallic components are used in the orthopedic field and it is known that
calcium phosphate coatings enhance bone attachment, there are many techniques for coat-
ing titanium with calcium phosphate. Ion sputtering is a process by which a thin layer of
calcium phosphate is transferred over to the titanium by directing an ion beam into a block
of calcium phosphate and vaporizing it to create a plasma that is recondensed on the metal
implant. Plasma spraying is a similar technique and is used commercially. Biomimetic
deposition through immersion of the metal part in a highly saturated solution of calcium
and phosphate, leading to deposition on the metal, is a way to make a calcium phosphate
coating with the most similar structure to actual bone mineral crystals.
Smooth surfaces such as pyrolitic carbon resist protein and cell attachment are ideal for
heart valve applications. Bioprostheses made of bovine or porcine heart valves are even
more superior for valve applications and reduce coagulation and embolism by a combina-
tion of an ideal surface topography and surface chemistry. However, they typically fail due
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