Biomedical Engineering Reference
In-Depth Information
with synthetic biomaterials. These synthetic resorbable polymers provide much
higher mechanical strength and are degraded by hydrolysis. Although synthetic
polymers can be produced and used for tissue engineering, the FDA-approved bio-
materials such as polylactic acid (PLA), polyglycolic acid (PGA), or mixture of
these two polymers are by far the most commonly used biocompatible polymers.
From the mechanical perspective, the Young's modulus of cortical bone is on the
order of ~10 GPa, and the Young's modulus for PGA closely matches this value
[~7 GPa (Yang et al.
2001
)]. In addition to providing the mechanical strength, syn-
thetic polymers can be manipulated to create and control the scaffold architecture.
This has become an important task in tissue engineering because (1) spatial organi-
zation of cell seeding and cell growth depends on the scaffold architecture and (2)
this architecture is now believed to regulate the development of specifi c tissue func-
tions. Cima et al. (
1991
) demonstrated that tissue regeneration using synthetic mate-
rials depends on the porosity and pore size of the scaffold. While large surface area
promotes cell attachment, large pores are desirable for providing suffi cient nutrients
and removing waste. Another aspect of the scaffold architecture is the degree of
continuity of the pores. Molecule transport and cell migration have been shown to
be prevented in the highly porous matrix of disconnected pores.
4.1
Microfabrication
Many techniques have been developed over the years to physically control and regu-
late the topographical features of synthetic scaffold. One prominent approach that
has become popular in the fi eld of tissue engineering includes microfabrication.
This technique relies on surface modifi cation of biomaterials via physical or chemi-
cal methods that can lead to desired cellular responses (Wilkinson et al.
2002
) .
Physical techniques, such as microcontact printing, casting, and embossing, have
been known for a long time, and also successfully been downscaled to micro- or
nanoworld (Curtis and Wilkinson
2001
). Microcontact printing, shown in Fig.
4
,
uses a lithographically fabricated stamp (usually from polydimethylsiloxane) with
the desired pattern, which can be inked with protein, polysaccharide, or other large
molecule. On pressing the stamp onto a substrate preconditioned with a sticky layer,
the molecule is transferred with the pattern of the stamp (Michel et al.
2002a,
b
) .
This simple and cost-effective approach results in chemical patterns with micron or
submicron size features displaying binding sites for specifi c molecules. Examples
of successful microfabrication applications include designing controlled drug deliv-
ery systems (Tao et al.
2003
), altering surface topography to mimic in vivo condi-
tions (Motlagh et al.
2003
) , microfl uidic fl ow (Popat and Desai
2004
) , and 3D
confi guration of multilayer cell cultures (Tan and Desai
2004
) .
Microfabrication techniques offer a useful tool to control selective cell adhesion
and spatial organization of cells in the 3D scaffold. Cell adhesion and motility is one
of the important biological processes involved in cell growth, differentiation, infl am-
matory response, and wound healing, and is often desired for engineering tissue
