INTEGRATING TOP-DOWN AND BOTTOM-UP SCAFFOLDING TISSUE ENGINEERING APPROACH FOR BONE REGENERATION - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 145

exogenous bioactive molecules to enhance regeneration. Many methods have been
developed to produce scaffolds with adequate properties as mentioned earlier based
on the top-down concept. An adequate processing technique should be performed on
selected biodegradable materials. A description and discussion of these techniques is
given in the following sections.

6.3.1.2 Processing Techniques Many techniques have been developed to prepare
porous ceramic, polymer, or composite scaffolds. Gel casting of foams is an early
developed technique for fabricating ceramic scaffolds with high mechanical
strength. 29-31 This technique commonly results in a poorly interconnected pore
structure and nonuniform pore size distribution; 32 however, these properties can be
improved by using a sol-gel material and a gel-casting hybrid process. 33 The ceramic
foam fabricated with this hybridmethod exhibited sponge-like structures with uniform
large pores and smaller pores distributed on the walls of the larger pores. The sizes of
big and small pores were within 500-800 and 50-300 m, respectively. 33

Replication of a polymer sponge is a typical technique for producing ceramic
scaffolds. 34,35 The replication method uses a sacrificial template (e.g., polyurethane
foam) coated by a ceramic (or glass) slurry. After drying the ceramic slurry, the
polymer template is slowly removed by thermal degradation, and the remaining
ceramic is further sintered. The process replicates the macrostructure of the starting
sacrificial polymer foam. 36-38 However, the low compressive strength of the scaffolds
produced by this method limits their application in the repair of load-bearing bone
defects. 39 Ramay and Zhang combined the gel-casting and polymer spongemethods to
produce porous hydroxyapatite scaffolds with high mechanical properties. 32 A com-
pressive modulus of 8 GPa and yield strength of 5MPa for the scaffold with
hydroxyapatite (HA) concentration of 50 wt% were achieved. 39 Fu et al. used a
newmethod of direct-ink-write assembly of a hydrogel-based ink to fabricate bioactive
glass scaffolds. Porous glass scaffolds with combined high compressive strength
(136MPa) and porosity (60%) were obtained, 40,41 which were comparable inmechan-
ical properties to those of cortical bone and a porosity comparable to that of trabecular
bone. The template-casting method is another technique that is used to produce porous
ceramic scaffolds 41 and polymer scaffolds. 42-44 Recently, Yang and coworkers
developed a template-casting technique to produce scaffolds with improved porous
structure and mechanical strength. Scaffold composition and architecture were
spatially regulated by controlling bead size and arrangement. 45-47
For producing porous polymer scaffold, solvent casting and particulate leaching is
the best known and most widely used method for the preparation of bone tissue
engineering scaffolds because of its simple operation and adequate control of the
pore size and porosity. After casting a dissolved polymer with a porogen, the
solidified polymer is placed in a water bath to leach out the porogen, thus yielding an
interconnected porous network. In this method, the particle size and amount of the
porogen can be controlled. However, this technique is not applicable to ceramic
scaffolds because the ceramic matrix obstructs complete removal of the porogen in
the leaching step, resulting in a less interconnected network. Ever since Mikos et al.
developed this technique to produce PLLA and PLGA polymer scaffolds, 48 many

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