Biomedical Engineering Reference
In-Depth Information
achieve suffi cient stiffness and strength in a highly porous structure to provide adequate mechanical
integrity. One of the most demanding applications is the repair and generation of musculoskeletal
tissues, particularly bone, where scaffolds need to have a high elastic modulus to provide temporary
mechanical support without showing symptoms of fatigue or failure, to be retained in the space they
were designated for, and to provide the tissue with adequate space for growth. One of the fundamen-
tal challenges of scaffold design and material selection concerns the achievement of high enough
initial strength and stiffness; the scaffold material must have both a suffi ciently high interatomic
and intermolecular bonding and a physical and chemical structure, which must in turn allow for
hydrolytic attack and breakdown,
in vivo
, as the scaffold degrades over time.
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Porosity
. A pore can be defi ned as a void space within a scaffold, whereas porosity can be con-
sidered as a collection of pores. Pore size and porosity are important scaffold parameters. Macro-
pores (
50 µm) are of an appropriate scale to infl uence tissue function, for example, pores greater
than 300 µm in size are typically recommended as optimal for bone in-growth in relation to vascu-
larization of the construct. Micropores (
>
50 µm) are of a scale to infl uence cell function (e.g., cell
attachment) given that mammalian cells typically are 10-20 µm in size. Nanoporosity refers to pore
architectures or surface textures on a nanoscale (1-1000
nm).
There is often a compromise between porosity and scaffold mechanical properties. Increasing
porosity may provide a greater pore volume for cell infi ltration and extra cellular matrix (ECM)
formation, but there is a concomitant decrease in mechanical properties in accordance with a power-
law relationship.
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Pore interconnectivity
. Pore interconnectivity is a critical factor and is often overlooked in
scaffold design and characterization. A scaffold may be porous, but unless the pores are intercon-
necting (i.e., voids linking one pore to another), they serve no purpose and become superfl uous
within a scaffold intended for tissue engineering. The interconnecting pore size is more critical
than pore size, and should be suitably large to support cell migration and proliferation in the initial
stages and subsequent ECM infi ltration of desired tissue. It is preferable that scaffolds for tis-
sue engineering have 100% interconnecting pore volume, thereby maximizing the diffusion and
exchange of nutrients (e.g., oxygen) and the eliminations of waste throughout the entire scaffold
pore volume.
Pore characterization
. As a measure of pore interconnectivity, the accessible pore volume,
or permeability, of a scaffold can be measured. Accessible pore volume can be defi ned as the
total volume of pores that can be infi ltrated from all peripheral borders to the interior of the scaf-
fold. Scaffold permeability can be measured by determining the fl ow rate of fl uid fl ow through
interconnecting pores. However, this technique is not suitable in scaffolds with large, 100%
interconnected pore volumes as the scaffold provides no resistance to fl uid fl ow. Alternatively,
accessible pore volume as well as vol.% porosity, pore size distribution, and scaffold surface
area to volume ratio (i.e., volume fraction) can be characterised using techniques such as mer-
cury intrusion porosimetry, microcomputed tomography (µCT), or image analysis.
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Mercury
porosimetry is a popular technique based on the principle that the pressure required to force a
nonwetting liquid such as mercury into pores, against the resistance of liquid surface tension, is
indicative of the pore size, assuming that the pores are cylindrical in shape. However, the resolu-
tion of the technique is severely limited in scaffolds with large pore sizes (
<
500 µm) where low
mercury intrusion pressures are necessary, and it has limitations when applied to materials that
have irregular pore geometries. Alternative techniques such as µCT have been developed for
analyzing bone architecture and more recently scaffold architecture to generate computer models
of porous materials. Using 3-D µCT techniques, a much greater amount of information can be
obtained to characterize pore architectures containing features ranging from 6 to
>
1500 µm,
without the physical limitations associated with mercury porosimetry.
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Scaffold fabrication is a
critical step in the production of an appropriate scaffold and an increasingly popular technique
for creating these tailor-made scaffolds in SFF.
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