Page 332 - IJB-9-1

International Journal of Bioprinting Review on Hybrid Biomanufacturing Systems

(ii) DLP . In DLP printing, a projector based on the is to fabricate a structure that can mimic the complexity
[16]
digital micromirror device (DMD) or liquid crystal and multi-material architecture of the native tissue.
display (LCD) serves as the source to project an entire A single biomanufacturing technique or a single material-
two-dimensional (2D) pattern for each layer, making based construct cannot realize the requirements for
the printing much quicker comparing to SLA. fabricating an ideal tissue construct, thus requiring the
(iii) 2PP . 2PP utilizes the two-photon absorption of improvements and combination of printing technologies
[17]
near‑infrared (NIR) light to excite the same energy as well as the development of advanced materials. An ideal
transition as UV photons. The polymerization process bioprinter should satisfy the following requirements: high
occurs when a molecule is excited from the ground resolution, high-viscosity material processing, fabrication
state to the excited state by absorbing two photons for of complex printed structures, high cell viability, multiple
an extremely short time interval. biomaterial processing techniques, affordability, and ease
of operation. Several biomanufacturing systems have
VP-based bioprinting process has been widely applied been developed for producing advanced hybrid tissue
for tissue engineering due to its superior resolution and constructs with improved properties. These sophisticated
accuracy, which is up to 20 m in SLA and DLP and up biomanufacturing systems can be divided into different
to sub-100 nm region in 2PP. This enables fabrication of categories due to the specific mechanisms incorporated:
biomimetic microenvironment that closely emulates the
complex extracellular matrices in native tissues, especially (i) Basic multi-head biomanufacturing systems (BMBSs)
[52]
[53]
in creating surface topology , hierarchical structures , (Figure 2A) use multiple printing techniques of
and high-resolution cell patterning . the same type, such as pneumatic extrusion or
[54]
inkjet. BMBSs have multi-head dispensing unit to
Lee et al. used an SLA system to fabricate neural selectively deposit different biomaterials and moving
[55]
scaffolds for nerve defects repair. The scaffolds contain in Z-direction, with the build platform moving in the
encapsulated poly (lactic-co-glycolic acid) (PLGA) X-Y plane.
nanoparticles with nerve growth factors, and the results (ii) Semi-hybrid multi-head biomanufacturing systems
showed an enhancement in the neurite regeneration and (SMBSs) (Figure 2B) are similar to BMBSs, but
improvement in the cell adhesion. DLP bioprinting has combine different types of material extrusion
been used to fabricate nerve guidance conduits with micro- techniques, such as pneumatic extrusion, piston
channels and the optimal elastic modulus is competitive extrusion, and screw-assisted extrusion. Hence, many
to that of the native nerves, which is in the range of 0.5 – types of biomaterials, including biomaterials of low
13 MPa . In addition to the applications in nerve repair, viscosity and high viscosity, can be processed by the
[56]
VP-based printing approaches have been used to fabricate SMBSs.
synthetic bone scaffolds with similar mechanical properties (iii) Fully-hybrid biomanufacturing systems (FBSs)
as the native bones (0.22 – 10.44 MPa) , presenting (Figure 2C) combine different AM techniques,
[57]
highly complex nanoscale structures. Furthermore, electrospinning, or post-processing techniques within
VP-based bioprinting techniques have the potential to the same system. This enables the fabrication of
overcome the limitations in skin generation by fabricating functionalized, complex tissue constructs of not only
high-resolution surface topography, for example, the multi-materials, but also in multi-scales.
physiological-relevant geometrical patterns to mimic the Although there is no specific consensus on the
mesenchymal and epithelial compartmentalization for definition of the term “hybrid processes,” researchers have
the regeneration of hair and other skin appendages . explored a number of approaches to combine different AM
[58]
Although the VP-based printing techniques have processes and post-processing processes with the similar
been well-established, due to the limited availability of objectives of improving the complexity, functionality, and
biocompatible materials, the application of this technique performance of printed tissue constructs. According to
in tissue engineering is still limited. With the development the above-mentioned definition, BMBSs are not hybrid
of bio-resin and improvement in the design complexity, it biomanufacturing systems since they are using the same
is promising for wider biomedical applications. biomanufacturing techniques, while SMBSs and FBSs are
3. Classifications of current biomanufacturing hybrid biomanufacturing systems due to the incorporation
systems of different AB techniques and post-processing techniques.
Tissue engineering aims for the repair and regeneration of 3.1. BMBSs
tissues and organs through the facilitation of guided cellular Various multi-head biomanufacturing systems have been
growth and regeneration. A key aim in biomanufacturing under development to dispense multiple biomaterials

Volume 9 Issue 1 (2023) 324 https://doi.org/10.18063/ijb.v9i1.646