Synthesis of Layered, Graded Bioscaffolds - Structural Interfaces and Attachments in Biology - page 341

Fig. 16.1 ESEM image of the pore structure of the CG scaffold ( T f ¼ 40 C). Scale bar: 100 m.

m

(Reproduced, with permission, from Pek et al. [ 38 ])

controllable biodegradation rates and products, native ligands to aid cell attach-
ment, and relatively weak antigenicity/immunogenicity [ 34 , 35 ]. GAGs were added
to the collagen material for several reasons beyond that of ECM biomimicry. First,
the co-precipitation of collagen with GAG increased the open-cell nature of the
scaffold, facilitating cell penetration and subsequent metabolic support; the CG
composite was also more resistant to degradation, thereby reducing the need for
heavy crosslinking that would otherwise leave the material brittle [ 35 ]. Not surpris-
ingly, the addition of GAG was also shown to significantly improve material
mechanical integrity [ 35 ]. While chondroitin sulfate remains the primary GAG
constituent, additional GAGs can be added for tissue-specific reasons, such as the
generation of a collagen-hyaluronic acid (HA) scaffold for cartilage tissue engi-
neering [ 36 ]. Homogenization and acidic co-precipitation (pH

3.2) of the collagen
with GAG content also destroys collagen's quaternary structure (without
denaturing the collagen). This resulted in unique hemostatic properties for CG
materials through the limitation of platelet aggregation in vivo normally associated
with collagen materials [ 35 ]. CG scaffolds are typically fabricated from a suspen-
sion containing between 0.5 and 1% w/v collagen and 0.05-0.1% w/v GAG [ 7 ].
These values were selected so that the resultant scaffolds have high porosities to
enable rapid cellular infiltration and diffusive transport processes, but also because
of the inherent difficulty in processing collagen-GAG suspensions with higher
solids content without denaturing the collagen due to the increased temperature
and shear stresses required for complete mixing.
The scaffold structure is created via lyophilization [ 7 ]. Briefly, the CG suspen-
sion is frozen at a specified temperature and rate [ 19 , 37 ], resulting in a continu-
ous, interpenetrating network of ice crystals surrounded by fibers of CG co-
precipitate termed struts. Sublimation of the ice crystals at a low vacuum

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