Page 329 - IJB-9-1

International Journal of Bioprinting Review on Hybrid Biomanufacturing Systems

Additive biomanufacturing (AB) provides the (iii) Vat photopolymerization refers to the UV curing of
capability to rapidly produce complex three-dimensional materials using a light source during the printing
(3D) structures with precision and reproducibility that process , including three main categories, namely,
[14]
exhibit functional gradients, multiple materials, and stereolithography (SLA) , digital light processing
[15]
exquisite control over pore size distribution within the (DLP), and two-photon polymerization (2PP) .
[16]
[17]
scaffold . The advantages of additive manufacturing (AM) These processes allow a wide range of biomaterials to be
[4]
within tissue engineering have facilitated the fabrication of deposited on the build platform by applying compressed air,
biomimetic and complex structures that more accurately light photopolymerization, thermal or mechanical effects.
reflect the in vivo environment. AM enables the precise Table 1 summarizes the advantages and disadvantages of
spatial deposition of biological materials, viable cells,
and biochemicals to fabricate 3D biological structures . each technique.
[5]
AB technologies have found extensive applications in the 2.1. Material jetting
biomedical area, including skin (for example, full-thickness
skin substitutes or wound dressings) , orthopedic , 2.1.1. Inkjet bioprinting
[7]
[6]
dental , osteochondral , cardiovascular , and other soft- Inkjet bioprinting, also known as drop-on-demand (DOD)
[9]
[8]
[10]
[10]
tissue engineering applications (e.g., pancreas and liver) . printing, uses a cartridge of a biomaterial solution and cells
However, the complexity of tissues and organs prohibits (bioink) to precisely deposit small droplets (20 – 50 µm) to
the use of a single technique due to limitations inherent to build up a multi-layer structure in a predesigned printing
each AM technology (e.g., relatively low printing resolution process. The size of the printed droplets is controlled by
and limited material applicability of specific technologies). the pressure pulses generated by a thermal or piezoelectric
For these reasons, hybrid biomanufacturing techniques, actuator .
[11]
combining different techniques and post-processes, have
been developed and subsequently applied in various fields The thermal inkjet-based systems use a rapid
during the last 5 years. In this review, we discuss the basic temperature increase controlled by a heating element
[18]
types of AB, advanced hybrid biosystems, and current and (ink temperature increase of up to ~300°C in a few µs
future applications. to generate vapor bubbles as the driving force to eject
ink droplets onto the substrate . The main concern
[19]
2. Additive biomanufacturing techniques associated with thermal inkjet is the negative effect of the
The process for material fabrication in AB includes the high temperatures during printing on the survival of the
[20]
following steps: raw material preparation, computer-aided biomolecules and cells to be printed . However, it has
scaffold structure design and lay down pattern definition, been evaluated and confirmed that the short heating pulse
program and G code generation by the control software, (~2 µs) only increase a few degrees in temperature and not
[21]
material deposition and if necessary, post-processing have a significant effect on cell viability . Piezoelectric
followed by extensive morphological, mechanical, and inkjet systems, based on the electromechanical system
biological characterizations for validation. According to (MEMS), use the pressure increase generated by applying a
[22]
ASTM standards, AB techniques can be classified in three piezoelectric change . Both methods present poor ability
main categories: material jetting, material extrusion, and to process bioinks with high density of cells, as cells tend
vat polymerization (Figure 1). to settle at the bottom of cartridge during the printing
process, resulting in the clogging of the print head and
(i) Material jetting refers to the technologies in which inhomogeneous distribution of cells . This may require
[23]
droplets of build and support materials are selectively cell agitators to be installed in the cartridge to prevent cell
jetted onto the build platform and cured by either sedimentation . Moreover, the thermal and shear stress
[24]
ultraviolet (UV) light or heat to form a 3D object. during the biomanufacturing process also negatively affect
Material jetting processes for biomanufacturing the cell viability. Due to this attribute, this technique is only
include inkjet bioprinting and laser-assisted limited to materials with low viscosity (<10 mPa·s) and low
[11]
bioprinting . 6 -1 [25]
[12]
(ii) Material extrusion refers to AM technique that uses cell concentration (<10 cells mL ) , and as a result, the
structures produced using this technique has relatively low
a continuous filament of thermoplastic or composite mechanical strength.
material to construct 3D parts. Three main extrusion
types have been widely used for biomanufacturing, The main advantages of inkjet printing include high
including pressure-assisted material extrusion, deposition resolution with a controlled droplet size that
piston-assisted material extrusion, and screw-assisted can be adjusted to about the size of one cell (~10 µm), and
material extrusion . high printing accuracy that can be tailored to <100 µm ,
[13]
[13]
Volume 9 Issue 1 (2023) 321 https://doi.org/10.18063/ijb.v9i1.646