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Composite Bioprinting for Bio-fabrication
generate micron-scale fibers and properly control the and electrostatic direct writing composite forming system.
fiber deposition position. However, electrostatic direct The system can achieve the preparation of bioconstructs
writing encounters challenges when constructing thick with stable mechanical properties as well as controllable
structures . According to recent studies, the composite cell distribution . Rajzer et al. used fused deposition
[31]
[43]
forming process based on electrospinning/electrostatic modeling (FDM) and electrospinning to prepare a kind of
direct writing and extrusion printing has emerged as layered scaffold for the reconstruction of nasal cartilage
a powerful technique in the field of developing new and subchondral bone. The upper layer of the scaffold was
scaffolds, including vessel, bone, and skin. made of osteogenon-gelatin by electrospinning to promote
Among various attempts, the most representative one cell adhesion and proliferation. The lower layer of the
lies in the preparation of the artificial blood vessel, which scaffold was prepared by printing poly-L-lactide with
contains the integration of micro-nano fibers generated FDM. The porous grid structure could not only provide the
by electrospinning and the macrostructure formed by mechanical strength for the scaffold as well as convenient
extrusion printing to mimic the multilayer structure in vivo fixation of the implant but also promote the tissue
[44]
of the blood vessel wall and regulate the mechanical growth and the penetration of gelatin . Diloksumpan et al.
properties [32-36] . Wu et al. utilized melt extrusion printing proposed a method to prepare bone cartilage scaffold by
and electrospinning to prepare a bi-layered vascular graft composite technology. In this method, PCL framework was
with 3D interconnected circumferential microchannels. constructed by melt electrowriting and then the printable
The bi-layered structure was fabricated by casting and calcium phosphate-based materials (pCaP) subchondral
electrospinning poly(l-lactic acid-co-ε-caprolactone) bone was directly built on the PCL layer by extrusion
while the microchannels in the inner layer were formed printing. After that, the cartilage was prepared by injecting
by sacrificing the extruded sugar fiber . By combining methacryloyl-modified gelatin (GelMA) into the former
[37]
electrospinning with melt extrusion printing process, framework. The experimental results showed that the
Lee et al. proposed a fabrication method of building a PCL framework improved the interfacial shear strength
composite artificial vessel which using electrospinning between GelMA and pCaP by 6.5 times. Furthermore, the
PCL membranes with highly-aligned fiber surface as the PCL grid embedded in GelMA increases the compression
inner layer and extruding PCL grid structure as the outer stiffness of the cartilage layer, increasing its resemblance
[45]
layer. After PDA coating and vascular endothelial growth to the natural one (Figure 2) .
factor immobilization, this vessel scaffold achieved good The composite forming method combining extrusion
mechanical properties and biocompatibility . Due to printing and electrospinning has been proven to be able
[38]
the tubular structure of the artificial blood vessel, most to effectively prepare the scaffold with a multiscale pore
of the composite printing process in this field can adjust structure, which has obvious advantages in realizing the
the properties by controlling the rotation of the receiving composite forming of multiscale micro-nano structures.
axis instead of the planning printing path by CAD/CAM. However, most of the existing research results are still
In the field of bone and skin-repairing, the limited in the use of biomaterials to prepare artificial
composite fabrication method containing electrospinning, regeneration scaffolds while the research on the direct
electrostatic direct writing, and extrusion printing has printing of cells, growth factors, and scaffolds materials
drawn lots of attention as it is capable of controllably to achieve the composite forming of active biological
shaping both macro and micro characteristics [39-42] . The structures is still at the stage of exploration.
core idea of this kind of technology is to take advantage 2.3. Combining cell printing and hybrid
of the respective characteristics of different processes. additive/subtractive manufacturing
Extrusion printing, capable of forming mesoscale
filaments, is chosen to provide mechanical support for Cell printing technology has advantages in achieving
the scaffold. Meanwhile, the microstructure formed by direct cell assembly, but most of the technologies with
sub-10-micrometer fibers can be readily manufactured high cell printing resolution are often unable to directly
by electrohydrodynamic processes. Along with the construct large-scale complex biostructures [46-49] . For
development of this technology and increasing fulfilment this reason, tackling this bottleneck requires combining
of various application requirements, this method has them with scaffold printing technologies. Due to the
begun using materials with different attributes. At the same complexity of the vascularization process, the use of
time, with the improvement of technology, the number of artificial biological tissue is limited to clinical application
cross-scale features is progressively increasing, putting at present [50-53] . It is necessary take into account the
this technology to great advantages for manufacturing requirements of cell metabolism in the process of preparing
bioconstructs with stable mechanical properties and biological structures and the role of scaffold materials,
controllable cell distribution. Recently, for the 1 time, cells, and growth factors from macro, meso, and micro
st
de Ruijter et al. verified the hydrogel extrusion printing scales [54-56] . In this context, as hybrid additive/subtractive
10 International Journal of Bioprinting (2021)–Volume 7, Issue 1