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International Journal of Bioprinting Review on Hybrid Biomanufacturing Systems

constructs (0.41 MPa). Bo et al. proposed a simple and required to be developed and improved. The development
versatile hybrid printing process using a screw-assisted of hybrid biomanufacturing systems and advanced print
AM technique combined with rotational electrospinning heads will be the main trend for the next decade. At present,
to fabricate dual-scale anisotropic scaffolds. 3D microscale since the hybrid printing systems are limited to extrusion-
porous PCL structures with highly aligned nanoscale fibers based techniques combined with electrospinning methods
were successfully produced in a layer-by-layer manner. and post-processing techniques, the incorporation of
The results showed improved cell distribution and tissue more AM techniques, such as SLA, will be considered
formation due to the controllable distributed electrospun for further exploration and inclusion in a hybrid system.
fibers . Another limitation is the poor capability of AM techniques
[89]
to print vascularization within the constructs, which
Liu et al. developed a plasma-assisted bioextrusion
system (PABS) , which is able to produce smart scaffolds warrants more investigations in the future. Moreover, as
[47]
using a multi-head extrusion system and perform surface the scale of the constructs are reducing to sub-micron or
modification in a layer-by-layer fashion using low- even nanoscale, imaging capabilities incorporated within
temperature plasma jetting. It comprises two pressure- the system can be considered for accurate control of the
assisted extruder heads, one screw-assisted extruder fabrication process. In addition, precise control over
head, and a plasma jet. Since many biopolymers are material properties during the printing is important so that
a temperature gradient control nozzle with precise control
hydrophobic, plasma treatment is necessary to manipulate of the crystallization process in semi-crystalline polymers
the surface chemistry of the polymer and tune properties,
such as wettability and cell adhesion. The plasma treatment to fabricate anisotropic structures can be considered.
enables the design and fabrication of scaffolds matching More advanced hybrid systems incorporating cell-
the mechanical properties and surface characteristics of culture systems can be developed for hospitals so that the
the surrounding tissue. PCL scaffolds with different zonal patient-specific tissue constructs are able to be produced
directly in the incubator and transplanted directly into
plasma treatments were fabricated. Wettability results the patients. The definition of biomanufacturing will be
confirmed that the hydrophilic character of the PCL
samples increased due to the nitrogen groups introduced by extended by incorporating material processing, printing/
the plasma jetting on the scaffold filaments. Furthermore, electrospinning, post-processing, and finally incubation
the plasma treatment positively influenced cell attachment and culturing bioreactor. To achieve this, it is imperative to
design biomanufacturing systems that are able to produce
and proliferation .
[90]
a specific organ, for example, heart, with specific modules,
5. Conclusions and future perspectives and tools for the application.
AB is a rapidly developing technology and is being Acknowledgments
widely applied in tissue engineering applications. Hybrid
biomanufacturing techniques utilizing multiple biomaterials None.
by combining multiple print heads or different printing Funding
techniques show great potential in fabricating multi-material
gradient scaffolds which better reflect the complexity of None.
native tissues and organs (summarized in Table 2). The Conflict of interest
available hybrid AM techniques can produce multi-material
scaffolds using different types of material filaments printed The authors declare that there is no conflict of interest.
with separate material chambers/cartridges, multi-scale
structures, and surface modification to introduce specific Author contributions
chemistries to the scaffolds. The printed structures using Conceptualization: Fengyuan Liu
these hybrid systems show improved behavior both in vitro Data curation: Rixiang Quan, Enes Aslan, Fengyuan Liu
and in vivo. Hybrid biomanufacturing systems are rapidly Supervision: Fengyuan Liu
expanding due to the demanding requirements of tissue Visualization: Rixiang Quan, Fengyuan Liu
engineering, which requires complex material handling and Writing – original draft: Rixiang Quan, Cian Vyas, Enes
processing to fabricate structures that resemble and mimic Aslan, Fengyuan Liu
native tissues and organs. Writing – review & editing: Fengyuan Liu, Cian Vyas
To mimic human tissues and organs, novel processing
methods and new routes to produce functional scaffolds with Ethics approval and consent to participate
adequate physical, chemical, and biological factors are still Not applicable.

Volume 9 Issue 1 (2023) 331 https://doi.org/10.18063/ijb.v9i1.646