Biomedical Engineering Reference
In-Depth Information
There are different cross-linking approaches to design degradable hydrogels
for biomedical applications [Hennik and Nostrum, 2002]. Biodegradable macro-
porous material prepared using synthetically adaptable cross-linkers offer a new
tool in designing the drug delivery systems and in tissue engineering. The majority
of biodegradable polymers belong to the polyester family. Among these poly(
-
hydroxy acids) such as poly(lactic acid), PLA, poly(glycolic acid), PGA and their
copolymers have been intensively used as synthetic biodegradable materials in a
number of clinical applications [Gunatillake and Adhikari, 2003; Hasirci et al.,
2001 ].
Design and manufacture of appropriate three dimensional (3D) scaffolds for
a particular application are of key importance in tissue engineering. The funda-
mental properties of scaffolds are their biocompatibility, adequate degradation
time, appropriate biodegradation rate (not too fast in a fi rst stage of contact with
cells and tissues) and proper porous microstructure. Depending on the tissue of
interest and specifi c application, the requirements for the scaffold material differ.
The materials should meet several requirements to be used as scaffolds for cell
applications. The open porous structure and interconnectivity of macropores are
needed for proper oxygen and nutrients delivery to cells, waste removal, vascular-
ization and tissue in-growth [Peters and Mooney, 1997]. Typically, cell scaffolds
should have a 3D porous structure and its porosity should be at least 90% in
order to provide a high surface area for maximizing cell seeding and attachment
[Cai et al., 2002]. Even the pore size is very type-specifi c. It is generally accepted
that pore size should be in the range of 10-400
α
m. Porosity can, however,
adversely affect important mechanical characteristics of a polymer, requiring
more complex material design. Pore size, shape, and surface roughness affect cel-
lular adhesion, proliferation and phenotype. Cells can discriminate even the subt-
lest changes in topography, and they are most obviously sensitive to chemistry,
topography, and surface energy [Burg et al., 2000]. Providing adequate mechani-
cal support is a critical requirement. The porous scaffold should have a mechani-
cal modulus in the range of soft tissues (0.4-350 MPa) [Hollister, 2005]. Scaffolds
made using traditional polymer-processing techniques, such as porogen leaching
or gas foaming, have maximum compressive module of 0.4 MPa [Hollister, 2005].
Classical approaches to synthesize the macroporous biomaterials include
freeze-drying [O'Brien et al., 2004, 2005; Patel and Amiji, 1996; Wan et al., 2007;
Yeong et al., 2007], porogenation [Wood and Cooper, 2001], microemulsion for-
mation [Bennett et al., 1995], phase separation [Liu et al., 2000; Nam and Park,
1999] and gas blowing technique [Kabiri et al., 2003; Sannino et al., 2006]. Recently,
the cryotropic gelation (cryogelation technique), implying the synthesis at sub-
zero temperature, was intensively employed for the preparation of macroporous
materials (known as
cryogels
) for biotechnological and biomedical applications
[Lozinsky et al., 2002; Kumar et al., 2003; Dainiak et al., 2006; Plieva et al., 2007a].
In most cases, the macroporous biomaterials with well defi ned porous struc-
ture are produced through freeze-drying technique [Wan et al., 2007; Yeong et al.,
2007] when the porosity is created by the sublimation of frozen solvent (most
frequently, water or dioxane), and the polymer is concentrated in the thin walls of
μ
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