Biomedical Engineering Reference
In-Depth Information
delivers periosteal cells in vivo and supports
osteochondral repair [
surface modifi cation technique is being widely
investigated [
80
].
21
,
38
,
83
].
6.3.2 Macrostructure
6.3 Scaffold Design
Properties
A porous scaffold permits cells to become part
of the porous void space. A porous scaffold is
also important for diffusion of nutrients and
waste removal. In general, it is advantageous
for the scaffold to have a high surface-area-to-
volume ratio. This promotes the formation of
pores with a diameter that is small but still
larger than the diameter of most cells. High-
porosity scaffolds have poor mechanical integ-
rity, and engineering for appropriate diffusion
and mechanical strength is an important chal-
lenge in their construction. Fiber meshes, foam
scaffolds, and hydrogels are examples of mate-
rials that provide added mechanical strength
to porous scaffolds.
Fiber meshes are formed into three-
dimensional structures by knitting or weaving
individual polymer fi bers, thus providing a
large surface area that promotes cell attach-
ment [
Scaffolds can be made to mimic the tissue that
is being regenerated. Aspects of the scaffold
that can be altered include the surface, the
macrostructure, mechanical properties, bio-
degradation, and biocompatibility.
6.3.1 Surface Properties
The majority of cell types used in bone tissue
engineering are anchorage dependent. The
engineered scaffold should therefore facilitate
cell attachment. The scaffold surface is the
initial and primary site of interaction with the
surrounding tissue. Scaffolds that cells can
attach to abundantly and easily with large,
accessible surface areas are favored. In addi-
tion, the scaffold surface should support cell
proliferation. Strong cell adhesion promotes
cell proliferation, and a rounded surface pro-
motes differentiation [
]. The structure of fi ber-mesh scaffolds
resembles that of the ECM, which allows for
nutrient diffusion and waste removal. The use
of fi ber bonding helps strengthen the mechani-
cal integrity of fi ber-mesh scaffolds [
97
]. Hydrophilic poly-
mers have highly wettable surfaces. This allows
cells to be encapsulated through capillary
action [
89
].
Foam scaffolds are generally prefabricated
before implantation. Similar to fi ber meshes,
their structure allows for adequate nutrient
diffusion and waste removal. Foam scaffolds
tend to be more stable than fi ber meshes but
still lack suffi cient mechanical integrity. Poros-
ity and pore structure can be modifi ed by using
different processing techniques, such as solvent
casting particulate leaching, melt molding,
freeze drying, and gas foaming.
Hydrogels are formed from hydrophilic
polymers by physical polymer entanglements
or cross-linking [
64
]. However, the most signifi cant
surface property of polymers is that they
provide an environment for scaffold-host
interaction. Many natural polymers can facili-
tate attachment because they contain func-
tional groups that vary in polarity, electrostatic
charge, hydrophobicity, and the ability to inter-
act by van der Waals forces. In addition, by
utilizing covalent and noncovalent assembly,
association constants can be varied and the
structure of natural polymers can be precisely
controlled [
23
]. The hydrophilic poly-
mers can absorb water up to a thousand times
their own dry weight [
33
,
36
]. In synthetic polymers, an
attempt is made to mimic the characteristics of
natural polymers. By altering polymer and
side-chain architecture, functional groups can
be made part of the surface or included within
the scaffold. For example, modifi cation of a
polymer with short peptide sequences or long
protein chains promotes interaction with the
surrounding tissue [
21
]. The aqueous envi-
ronment created in hydrogels simulates the in
vivo environment and therefore provides an
ideal setting for cell encapsulation. In addition,
the aqueous environment supports quick dif-
fusion of nutrients, proteins, and waste, thus
promoting cell growth and proliferation. Some
hydrogels, including PEG-based hydrogels, are
easily injectable and capable of being molded,
allowing minimally invasive implantation [
36
]. Specifi cally, ligands
that are common in the extracellular matrix,
such as fi bronectin, vitronectin, and laminin,
have been used as surface molecules [
83
].
The disadvantages of hydrogels are that they
25
83
]. This
