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Additive manufacturing of bone scaffolds
Several thermoplastic polymers were used to fabricate of ketoprofen, a non-steroidal anti-inflammatory
electrospun scaffolds for bone tissue engineering, such drug for local chemotherapy [186] . Kolambkar et al. [187]
as PCL [172] , PLGA [173,174] , and PLA [175] . For instance, Shim fabricated the electrospun PCL nanofibrous scaffolds,
et al. [176] reported electrospun PLLA fibrous scaffolds, which contained a growth factor delivery system for
which were proved to be desirable substrates for cell stable release of recombinant bone morphogenetic
growth and bone construction, while Vaquette et al. [177] protein-2 (rhBMP-2). It was found that the delivery
produced electrospun PCL scaffolds and investigated system provided a consistent release of rhBMP-2 in
the cell adhesion. It was observed that a dense cell the fibrous structure, which effectively induced the
sheet formed on the top and bottom of the samples bone formation. More comprehensive review regarding
cultured in osteogenic media (Figure 10C). However, the area of using electrospun nanofiber scaffolds as a
microcomputed tomography analysis revealed the drug delivery system can be seen in Wang et al. [171] and
slow bone regeneration until implantation for 8 weeks Bagchi et al. [183] .
(Figure 10D). Yao et al. [178] prepared 3D electrospun PCL
and PCL/PLA nanofibrous scaffolds, which exhibited a 4. Post-treatments
high porosity of ~95.8% and interconnected and multiscale Although the porous scaffolds fabricated by AM can
structure with pores sizes ranging from submicrometers achieve the analogous porous architecture of natural
to 300 μm. Compared to PCL scaffolds, PCL/PLA bone, their various properties, especially mechanical
scaffolds exhibited enhanced mechanical properties and properties and biological characteristics, are commonly
bioactivities. In fact, the synthetic nanofibrous scaffolds lower than expectation. Therefore, post-treatments
with relative low mechanical strength and poor ability are commonly needed to enhance the comprehensive
to interact with cells have difficulty in meeting the performance of AM processed scaffolds so that they can
requirements of bone repair. Thus, researchers attempted reach the requirements of bone tissue repair. Summarizing
to prepare biphasic composite nanofibrous scaffolds the previous literature, the post-treatment technologies
with an improved comprehensive performance. Tan applied in AM-processed scaffolds can be classified into
et al. [179] obtained PCL and gelatin-blended scaffolds two categories, including heat treatment and surface
by electrospun, as shown in Figure 10B. It was found treatment, which are fully reviewed in this chapter.
that PG73 scaffold (PCL: gelatin ratio of 70:30) spun
at high flow rates was more favorable for cell growth 4.1. Heat Treatment
and retention. Besides, Li et al. [180] reported electrospun
composite nanofibers composed of mesoporous silica Heat treatment is a way to improve the performance by
nanoparticles and chitosan. The incorporation of modifying the microstructure. In extrusion process, solid
mesoporous silica nanoparticles was proved to enhance ceramic particles are generally mixed with a solvent to
the mechanical properties and promote biomineralization form slurry, then extruded through the nozzle, and directly
ability of the scaffolds. In addition, Lin et al. [181] reported built into scaffolds. Such green scaffolds inevitably have
electrospun PLGA/HAp/Zein scaffolds, which exhibited extremely loose structure and resultant poor mechanical
excellent ability to promote in vivo cartilage formation. property. Thus, the heat treatment is essential to sinter
Bagchi et al. [182] incorporated three different perovskite and consolidate the solid particles together, with an aim
ceramic nanoparticles into PCL nanofiber, resulting in to improve the mechanical properties. Aleni et al. [188]
an enhanced expression of osteogenic genes. It is noted used extrusion method to fabricate TiO scaffolds with
2
that an excess addition of nanoparticles would disrupt bentonite powder (2 wt.%) as the binder and water
the formation of polymer fiber, leading to deteriorated (35 wt.%) as the solvent. To harden the scaffolds, they
mechanical behavior. were sintered at 1200–1300°C for 4 h with heating and
The electrospun fiber scaffolds also show great loading cooling rates of 10°C/min. Mechanical tests revealed
and encapsulation capacity of various drugs or small that the elastic modulus of TiO scaffolds after post-heat
2
molecules because of their characteristic nanoscale treatment ranged from 2.08 to 5.90 GPa, which was close
morphological structure [171,183] . For electrospun nanofiber to that of high-density cancellous bone. Huang et al.
drug delivery system, it possesses greater permeability [189] used HA/TCP composite ceramic slurry to fabricate
to allow shorter response time and more precise control scaffolds by extrusion method. HA and TCP powders
over the release rate. Thus, a large amount of bone were dissolved in the solvent, which consisted of 30 vol.%
scaffolds containing various drugs or small molecules, glycerol and 70 vol.% deionized water. After extrusion,
such as anticancer drugs, antibiotics, polysaccharide, the composite scaffolds were sintered at 400°C to burn
and proteins, was constructed to achieve a controllable out the glycerol before sintering at 1200°C to increase
drug delivery into defective bone tissues [184,185] . For the densification rate. Results showed that scaffolds with
example, electrospun PCL fibers were used as carriers good chemical stability had no new phase formed during

14 International Journal of Bioprinting (2019)–Volume 5, Issue 1