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Additive manufacturing of bone scaffolds
FDM, also known as extrusion-based processes, was first Figure 7B. The scaffolds exhibited close mechanics to
put forward by Crump in 1988. In FDM, the materials are that of natural bone in regard to structure feature and
heated up until flowing before extruding or squeezing out chemical composition. In vivo assays confirmed their
of a nozzle. The extruded fluid subsequently deposited enchanted biodegradability and improved new bone
on the substrate with a layer-wise pattern based on the formability (Figure 7C, 7D and 7E), as compared to
motion of the nozzle in each layer; then, a 3D scaffold pure PCL scaffolds. Besides, Kim et al. [140] produced a
is built layer by layer. A diagram for the FDM process is scaffold composed of polylactic-co-glycolic acid (PLGA)
depicted in Figure 7A. The accuracy of extruded scaffolds and β-TCP by FDM. After 12 weeks’ implantation, the
greatly depends on the printing nozzle. scaffolds integrated tightly with the surrounding bone
FDM technology is mainly applied to process low-fusing tissue, indicating their good biocompatibility. Poh et al.
temperature polymer. Hutmacher et al. [130] reported a use [141] fabricated composite scaffolds containing PCL and
of FDM to fabricate porous scaffolds with PCL, which bioglass by FDM. Interestingly, in vitro tests revealed
presented 0°/60°/120° orientation patterns with the that the composite scaffold showed an upregulation of
porosity more than 56% and pore sizes ranging from 380 osteogenic gene expression. In addition, it was found
to 590 μm. Zhou et al. [131] fabricated hierarchical polymer that the host tissue infiltrated well into the scaffolds
scaffolds with macropores between 100 and 800 μm after 8 weeks’ implantation into the nude rats. Though
through the FDM. It was demonstrated that porosity introducing bioactive ceramics can improve the biological
printing errors between the obtained scaffolds and the properties of polymer scaffolds but also brings other
designed model were <5%, indicating that FDM is an concerns. During FDM of composites, the incorporated
efficient technology to obtain scaffolds with a relative bioceramics with higher melting point exist in solid
high accuracy of pore structure. Tellis et al. [132] combined phase, which will increase the viscosity and reduce the
micro-CT and FDM to produce polybutylene terephthalate fluidity of the slurry and ultimately reduce the accuracy
scaffolds before applying for trabecular repair. Kosorn and efficiency of the molding. On the other hand, due to
et al. [133] reported that PCL/poly(hydroxybutyrate-co- the different shrinkage characteristics, a large number
valerate) (PHBV) blended porous scaffolds fabricated by of pores will form between the ceramic particles and
FDM, founding that the compressive strength increased matrix, which greatly reduces its mechanical properties.
with incorporated PHBV increasing. Composite scaffolds Therefore, a further process is required to compensate for
based on PCL and poly(ethylene glycol) (PEG) were also mechanical properties loss.
fabricated by FDM [134] .
Recently, polymers with a relative high melting point 3.4. EBM
have also been utilized in FDM. For example, polyether
ether ketone (PEEK) with superior melting point between A B
330°C and 340°C was developed into scaffolds with a self-
developed FDM system [135] . In this system, the syringe
consists of two different metal tubes, including a brass tube
with an internal diameter of 17 mm attached to a 500 µm
nozzle and a stainless steel tube. The brass tube with a good
thermal conductivity was able to help PEEK absorbed
sufficient energy to get fully melted. Controlling the nozzle
temperature between 400°C and 430°C and the extrusion
rate of 2.2 mg/s, PEEK scaffolds with 38% porosity were
successfully obtained, which showed a compressive yield
strength of 29.34 MPa and a compressive yield strain C
of 4.4%. Furthermore, Rinaldi et al. [136] also reported a
potential usage of FDM in fabricating PEEK scaffolds.
However, with high melting point polymers in FDM,
severe shrinkage, warpage, and delamination normally
occur due to the sharp temperature gradient caused by
the relative high extrusion temperature. Therefore, it is Figure 8. (A) A schematic diagram for electron beam melting
(EBM) equipment. (B) Micro-computed tomography images
necessary to control the cooling process in FDM. showing the geometry of EBM-processed scaffolds, and scanning
FDM has also been reported for the preparation of electron microscope images showing the responding roughness
polymer and ceramic composite scaffolds [137,138] . Xu et al. surface [147] . (C) Undecalcified toluidine blue stained images
[139] used CT-guided FDM to fabricate PCL/HA bones showing the pattern of bone formation after the implantation of
scaffolds with cortical bonelike features, as shown in EBM-derived Ti6Al4V and CoCr scaffolds.

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