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Full text of "Bio-Inspired Materials: Exhibited Characteristics and Integration Degree in Bio-Printing Operations"

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American Journal of Engineering and Applied Sciences 


Bio-Inspired Materials: Exhibited Characteristics and 
Integration Degree in Bio-Printing Operations 

Antreas Kantaros 

Department of Industrial Design and Production Engineering, University of West Attica, Greece 

Article history Abstract: In the last decade, additive manufacturing techniques, commonly 
Received: 25-10-2022 known under the term "3d printing" have seen constantly increasing use in 
Revised: 16-11-2022 various scientific fields. The nature of these fabrication techniques that 
a operate under a layer-by-layer material deposition principle features several 
de facto advantages, compared to traditional manufacturing techniques. 
These advantages range from the precise attribution of pre-designed complex 
shapes to the use of a variety of materials as raw materials in the process. 
However, its major strong point is the ability to fabricate custom shapes 
with interconnected lattices, and porous interiors that traditional 
manufacturing techniques cannot properly attribute. This potential is 
being largely exploited in the biomedical field in sectors like bio-printing, 
where such structures are being used for direct implantation into the 
human body. To meet the strict requirements that such procedures dictate, 
the fabricated items need to be made out of biomaterials exhibiting 
properties like biocompatibility, bioresorbability, biodegradability, and 
appropriate mechanical properties. This review aims not only to list the 
most important biomaterials used in these techniques but also to bring up 
their pros and cons in meeting the aforementioned characteristics that are 
vital in their use. 

Email: akantaros 

Keywords: 3D Printing, Bio-Printing, Biomaterials, Fused Deposition 
Modeling (FDM), Stereolithography (SLA) Direct Ink Writing (DIW) Laser- 
Guided Direct Writing (LGDW) 

Introduction Bio-printing is the additive process of creating cell 
patterns by successively depositing cells along with 

Additive manufacturing, most commonly referred biomaterials that form a substrate thereby fabricating 

to as "3D printing", can be described as the additive living human constructs with similar biological, chemical 
process where a three-dimensional object is fabricated and mechanical properties for proper recuperation of 
by laying successive material layers at controlled speed tissues, scaffolds and organs. Materials used in this 
and layer thickness. These materials can be process are known as biomaterials and should exhibit 
biomaterials, metals, ceramics, plastics, resins, biocompatibility, i.e., being compatible with the human 
concrete, or other materials. Even though printing time, body, bioresorbability, i.e., being able to be naturally 
processing speed and printing resolution have been absorbed by the human body, biodegradability 1.e., the 
constantly improving over recent years, still, the lack capacity for biological degradation and appropriate 

mechanical properties dependent on the implantation spot 
(Bielenstein et al., 2022; Kowalewicz et al., 2021; Guo et al., 
2022; Kantaros et al., 2016). 

In this context, the field where the aforementioned bio- 
printing technique is growingly being adopted is tissue 
engineering. Tissue engineering is an innovative, 

of variety in 3D printable materials persists. Emerging 
fields like 3D printing of biomaterials, 3D printing of 
tissues, and high viability cell printing are highly 
dependent upon printing ink’s compatibility and 
flowability with the current printing techniques 

available. This study Heponts the advances in 3D printing multidisciplinary field that incorporates the fundamental 
materials for emerging biomedical fields and their principles of engineering and biology to invent structures 
compatibility with currently available printing techniques. with elevated biological functions. Regarding clinical 

Y, Science © 2022 Antreas Kantaros. This open-access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 
: : li ; 
U3 Publications icense 

Antreas Kantaros. /American Journal of Engineering and Applied Sciences 2022, 15 (4): 255.263 

DOI: 10.3844/ajeassp.2022.255.263 

applications, one of the most decisive targets of tissue 
engineering is to surpass the numerous barriers imposed 
by current treatments that are currently based mainly on 
organ transplants and biomaterial use for implantation 
(Guillotin and Guillemot, 2011). Organ and _ tissue 
malfunctions are a major problem regarding human health 
and well-being. Especially in cases where the human body 
fails to self-heal using its mechanisms, targeted medical 
intervention is crucial. 

Even though tissue engineering may be newly 
introduced, the initial concept of tissue substitution was 
first expressed in the 16th century. Gasparo Tagliacozzi 
(1546-1599), Professor of Surgery and Anatomy at the 
University of Bologna, can be considered as the 
initial/first documented relevant case when he managed to 
construct a nose replacement by a forearm flap in “De 
Custorum Chirurigia per Insitionem” announced in 1597 
(O'brien, 2011). The primal clinical application of human 
cells in this field involved skin tissue development by 
utilizing fibroblasts, keratinocytes, or a scaffold (that 
would act as a tissue substrate). In another published 
work, the regeneration procedure of rabbit articular 
surfaces by utilizing allograft chondrocytes along with 
collagen gel is also reported (Wakitani ef al., 2002). A 
published literature work by Langer and Vacanti (1993) 
named "Tissue Engineering" is considered a_ great 
contribution towards advancing tissue engineering research 
on a worldwide scale (Ikada, 2006). 

The first decade of the current century is linked with 
the first successful cases of developing the first solely lab- 
grown organs by utilizing 3D_ bioprinters. The 
contribution of Anthony Atala is considered fundamental 
in this field, where cell therapies, tissue engineering 
constructs, and organs for many diverse areas of the body 
have been developed (Anthony, 2022). In addition, he is 
attributed with the development of 3D _bioprinters 
(Murphy and Atala, 2014) and, in 2006, he and his team 
developed the first lab-fabricated organ (a human bladder) 
for implantation to humans (Atala et al., 2006). Dr. Paolo de 
Copp1’s work is also fundamental in this sector, where 
a tissue-engineered tracheal replacement for a child 
being developed by him and his team was reported 
(Elliott et al., 2012). 

Lattice tissue engineering structures fabricated by bio- 
printers and compatible biomaterials must exhibit a 
variety of desired characteristics in the sense of providing 
a proper substrate for 3D tissue development as the final 
target. More commonly referred to as "scaffolds", they act 
as bioresorbable constructs in the spot of the defect with 
the role of cell-encapsulated tissue constructs containing 
cells/hydrogels (Dong et al., 2017; Nicodemus and 
Bryant, 2008). They can be categorized as "acellular 
scaffolds" (scaffolds with no cells, like hip and knee 
implants, etc.) or "cellular scaffolds" (scaffolds with cells, 
like skin constructs). Bio-printed scaffolds should exhibit 


the desired mechanical behavior in terms of providing 
mechanical integrity in the healing and degradation 
periods. Controlled porosity is also desired, where an 
interconnected pore network is considered crucial for 
blood and nutrient flow. The aforementioned dictates the 
ability for scaffold fabrication in well-defined geometrical 
shapes (Kantaros and Piromalis, 2021). Bio-printing 
techniques exhibit high potential in this field, by being 
able to provide dimensional stability, reproducibility, and the 
fabrication of pre-designed interconnected porosity networks 
at distinct sizes (Moroni et al., 2006; Amirkhani et al., 2012). 
Several published works describe cases of bio-printed 
scaffold structures (Moroni et al., 2006; Leong et al., 2003; 
Gauvin et al., 2012; Kantaros, 2022). Stages of the bio- 
printing process are depicted in Fig. 1. 

3D Bioprinting Techniques 
Stereolithography (SLA) 

SLA printing is a 3D printing technique that uses a 
laser or a DLP projector to cure photopolymer resin 
layer-by-layer. SLA 3D printers use a UV laser or a 
DLP projector to cure a specific layer of photosensitive 
resin in a tank. The light source cures or hardens the 
resin, forming a very thin sliced solid layer. This slice 
bonds to the previously formed layer or the build plate. The 
build plate then moves away from a value that equals the pre- 
determined layer thickness. This is how the process of object 
formation is repeated until the complete object is created. 

SLA printing produces higher resolution than FDM 
printing because it uses a light source to solidify the 
material, resulting in small-sized prints. The horizontal 
resolution of an SLA scanner depends on the size of the 
light source spot and can range from 30 to 140 microns. 
The vertical resolution (or Z-direction resolution) varies 
from 25 to 200 microns (Jo and Song, 2021). To create a 
good print, you need to set the layer height and the support 
placement correctly. Figure 2 depicts an SLA 3D Printer 
apparatus schematic. 

Ink materials compatible with the SLA process should 
exhibit properties like biocompatibility, stability under 
exposure to UV light, low viscosity, and optical 
transparency (Rasheed ef al., 2021). 


Fig. 1: Distinct stages of the bio-printing process 

Antreas Kantaros. /American Journal of Engineering and Applied Sciences 2022, 15 (4): 255.263 

DOI: 10.3844/ajeassp.2022.255.263 

x-y scanning motor 

Light source 

Platform moving assembly 

Z Printed part 

se Resin tank 


Fig. 2: Stereolithography 3D Printing schematic 

Bio-Inks Compatible with SLA Process 
Poly (D, L-Lactide) (PDLLA) 

PDLLA is a versatile polymer with many applications 
in the medical field, including as a scaffold material for 
tissue engineering, as a controlled delivery system for 
drugs, and as synthetic nerve conduits made out of 
PDLLA, B-TCP, and collagen for regeneration of 
peripheral nerves (Hofmann et al., 2012; Lin et al., 2006; 
Lin et al., 2017). 

Literature works describe the fabrication of composite 
scaffolds from HA biocement embedded in PDLLA 
oligomers using SLA 3D printing technology using ethyl 
2,4,6-trimethylbenzoylphenylphosphinate as a 
photoinitiator and N-Methyl-2-Pyrrolidone (NMP) as a 
diluent. With increasing percentages of ceramic in the 
resin, the viscosity of the resin increases and so a non- 
reactive diluent, such as NMP, is necessary to help 
maintain the desired viscosity for SLA. It has been found 
that as the concentration of HA powders increases, the 
elasticity of the material increases. (Cai et al., 2019). 

Poly (Propylene Fumarate) (PPF) 

PPF is used in SLA due to exhibiting pho-to-cross- 
linkability. It is also biodegradable and possesses elevated 
mechanical properties. In the majority of cases, it is being 
used in SLA by creating a solution consisting of PPF as 
the base polymer and Diethyl Fumarate (DEF) as a 
solvent. The solvents were used in an attempt to avoid 
premature crosslinking of the polymer. Along with the 
above-mentioned solution, a photoinitiator is required in 
SLA. In this case, bisacryl phosphrine oxide is used. A 
proper balance between PPF and DEF is essential. It has 
been observed that with a ratio higher than 0.5 of PPF to 
DEF mechanical strength decreases significantly. On the 
other hand, adding DEF decreases the viscosity of the 
solution and hence improves printability. The recent 


introduction of a ring-opening polymerization method 
allows the precise determination of PPF molecular mass, 
viscosity, and molecular mass distribution. Decreased 
molecular mass distribution assists in the time-certain 
resorption of the fabricated structures. Newly introduced 
post-polymerization and post-processing functionalization 
methods have increased the number of biomedical 
applications that use PPF material. 

Recently, literature works suggest that the influence of 
PPF molecular mass in scaffolds fabricated via the SLA 
technique proved critical regarding the degradation rate 
and bone regeneration in vivo. PPF with lower mass 
exhibited finer behavior in healing rates while no 
inflammation and host cell acceptability were reported 
(Kondiah et al., 2020; Mamaghani et al., 2018). 

PEGDA and GelMA Inks 

Literature works report the use of SLA-based 3D bio- 
printing for a novel cell-laden cartilage tissue 
construction. The resin used was comprised of 10% 
Gelatin Methacrylate (GelMA) as base material, various 
percentages of Polyethene Glycol Diacrylate (PEGDA), 
biocompatible photo-initiator and trans-forming growth 
Factor-Beta 1 (TGF-B1) embedded nanospheres fabricated 
via a core-shell electrospraying technique. It was found that 
adding PEGDA to GelMA hydrogel greatly improved 
printability while compressive modulus also elevated 
proportionally with PEGDA whilst the swelling ratio 
decreased. Cells grown on 5/10% (PEGDA/GelMA) 
hydrogel present the highest cell viability and 
proliferation rate. The TGF-B1 embedded in nano- 
spheres can keep a sustained release for up to 21 days 
and improve the chondrogenic differentiation of 
encapsulated MSCs. Therefore, such materials feature 
high potential in cartilage regeneration processes 
(Martinez-Garcia et al., 2022; Jiang et al., 2022). 

Fused Deposition Modeling (FDM) 

In this technique, the material is led to the extrusion 
nozzle as a liquid of predefined viscosity or it is melted by 
the heated nozzle to form a layer on the build platform. The 
required ink is fabricated in the form of a solid filament 
which is then heated to a semi-molten state in the stage of 
extrusion. A temperature-controlled nozzle then oozes out 
the filament material. The forced-out extruded material is 
deposited onto a platform in a layer-by-layer deposition 
principle. After completing one layer, the platform gets 
lowered further and then the next layer gets deposited. The 
main parameters decisively contributing to the final 
properties of the material are layer thickness or height, 
printing speed, infill percentage, nozzle temperature, 
retraction, shell thickness, and support potential presence 
(Kantaros and Karalekas, 2013; Antreas and Piromalis, 
2021; Kantaros et al., 2022; Kantaros and Karalekas 2013; 
Tsaramuirsis et al., 2022; Kantaros et al., 2013). 

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Filament is led 
to the extruder 


The extruded material is laid down 
on the model where it is needed. 

The print head and/or bed is moved 
to the correct X/Y/Z position for placing 
the material 

Fig. 3: Fused Deposition Modeling (FDM) schematic 

Figure 3 depicts a Fused Deposition Modeling (FDM) 
3D Printer apparatus schematic. 

The majority of FDM printers are compatible with a 
wide range of inks. However, the viscosity should be 
greater than 6 x 10’ MPa/s, they should be molten at 
temperatures between 200 and 250°C and a fast rate of 
solidification is needed to melt them. In addition, the ratio 
of elastic modulus to melt viscosity should be less than 
5x 10°s1. 

Bio-Inks Compatible with FDM Process 
Poly (Caprolactone) 

PCL has properties that make it well-suited for 
melt-based extrusion processes. The low acquisition 
cost and shear-thinning properties of this material make 
it well-suited for use in medical devices and its thermal 
stability makes it a desirable choice for medical 
applications. Published literature works suggest that 
PCL can be used to fabricate a tissue-engineered 
scaffold to be used as a restoration substrate of breast 
tissue after a partial mastectomy operation (Jwa et al., 
2022). Other reported literature cases indicate the use 
of PCL material combined with sodium Mesoglycan 
(MSG) which exhibited high rates in targeted wound 
healing (Liparoti et al., 2022) and the design and bio- 
printing of a novel wound-dressing material by 
incorporating Juglone (5-hydroxy-1,4- 
naphthoquinone) to a 25% Polycaprolactone (PCL) 
scaffold (Ayran et al., 2022). 


Poly (Lactic Acid) 

Polylactic Acid (PLA) is one of the most commonly 
used polymers for FDM due to advantages such as 
biocompatibility, biodegradability, and low cost. The 
melting point temperature of this material makes it 
suitable for forming filaments and it can be extruded at a 
temperature of 180-250°C (Kantaros et al., 2021). One of 
the challenges with PLA is the release of acidic by- 
products when it degrades. There was a significant 
decrease in the physiological acidity level due to the 
release of lactic acid. To reduce the likelihood of acidic 
release, PLA and ceramics are combined to create a 
composite material. The composite material also tends to 
increase the strength of compressive forces, making it a 
good candidate for tissue engineering processes. 

Polyether Ether Ketone (PEEK) 

Peek is a semi-crystalline thermoplastic polymer that 
has a melting temperature between 330-340°C and a 
service temperature of 260°C (Ikada, 2006). Due to its 
high melting point, it was initially excluded from its use 
in FDM processes. Recent advances in FDM printer 
technology have allowed the use of PEEK in FDM 
printers. Published literature suggests that the main 
factors affecting the 3D printing of PEEK in FDM 
processes are the melting point temperature, the extrusion 
speed, and the extrusion force. (Dorovskikh ef al., 2022). 

Poly-Vinyl Alcohol (PVA) 

Poly-Viny] Alcohol (PVA) is a synthetic polymer created 
by vinyl alcohol and acetate monomers. The presence of the 
latter provides biocompatibility, biodegradability, and bio- 
inertia. PVA is soluble in lukewarm water and can be used in 
FDM techniques in filament form. The tensile properties of 
this material are highly comparable to those of human 
articular cartilage, thus, providing a suitable substrate for 
bone cell ingrowth (Chua et al., 2004). Its hydrophilicity and 
chemical stability allow extreme pH and temperature 
exposure and its semi-crystalline form ensure proper oxygen 
and nutrients flow to the cell. PVA is extensively used in 
various load-bearing implant cases like cranio-facial defects 
and bone tissue regeneration treatments (Oka et al., 2000). 

Direct Ink Writing (DIW) 

DIW is an extrusion-based 3D printing exhibiting 
similarities with the FDM method that uses a nozzle to 
extrude materials onto a build platform in a layer-by-layer 
manner. By utilizing this technique, controlled deposition 
of raw materials in a highly viscous liquid state is 
achievable which allows them to retain their shape upon 
the deposition stage. DIW can be considered more 
versatile than FDM as it can use a large variety of 
materials ranging from ceramics, hydrogels, plastic, food, 
and even living cells. The prime parameters which decide 
the final properties of the product are nozzle size, 

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viscosity and density of the material, printing speed, and 
thickness kept between the layers. In DIW, similarly to 
FDM, the use of support structures is vital in cases of 
complex geometrical shapes featuring overhangs and 
steep deposition angles. However, the use of dissolvable 
materials as supports helps towards overcoming this issue 
due to their ability to be easily removed upon the 
completion of the printing procedure. The post- 
fabrication processing stages also assist in the elevation of 
the printed item’s mechanical properties (such as 
elastic modulus) by using UV-curing apparatus 
(Shuai et al., 2013a-b). Figure 4 depicts a Direct ink 
writing schematic 

Ink materials using the DIW method should exhibit a 
fast rate of gelation and maintain proper structural 
integrity upon the completion of the printing process. 

Laser-Guided Direct Writing (LGDW) 

LGDW is a laser-assisted direct writing technique that 
is capable of depositing cells with micrometer accuracy. 
The technique of cell deposition using a weakly focused 
laser beam can be used on a variety of surfaces and 
matrices. Laser-guided bio-printing is a process in 
which a laser beam is used to direct cells onto a 
receiving substrate (Bunea et al., 2021). 

Bio-Inks Suitable for DIW and LGDW 
Hydrogel Inks 

Hydrogels are complex three-dimensional networks of 
hydrophilic polymers that can absorb a large amount of 
water. The key advantage of those materials is their high 
biocompatibility and biodegradability rates because of 
their ability to supply the proper conditions that favor the 
encapsulation of viable cells further protecting the cells 
without hindering cell-cell interaction. Hydrogel inks 
should be able to flow fluently under working pressure 
conditions by exhibiting controlled viscosity. Also, they 
ought to provide sufficient structural integrity upon the 
completion of the printing, furthermore as a fast rate of 
gelation which will be controlled by exploiting shear 
thinning (Tamo ef al., 2022). The literature desired 
approach to design a hydrogel ink is to fabricate a polymer 
solution that forms a network upon the completion of the 
printing process. The network thus formed could be 
physically or chemically crossed-linked using external 
stimuli like temperature, light, or ion concentration 
(Rioux ef al., 2022). The majority of natural polymers 
such as gelatin, cellulose, collagen, fibrinogen, alginate, 
and agar and synthetic polymers such as polyacrylamide, 
polyurethane, Polyethene Glycol (PEG) are being utilized 
in hydrogel fabrication in 3D __ bio-printing 
(Ramezani et al., 2022; Teixeira et al., 2022). 

The rate of proliferation towards the targeted tissue 
decreases as the polymer concentration and cross-linking 


density increase. However, due to their increased 
viscosity, higher polymer concentrations are ideal for 
extrusion-based DIW. Mechanical properties increase as 
polymer concentration increases. Shear stress rises with 
viscous inks, high pressure, and small diameter nozzles 
and can cause cell death during extrusion. Shear stresses 
greater than 60 MPa have been found to cause 35% or 
more cell death (Duan, 2017). Thus, when using the DIW 
technique, shear stress is the most important parameter 
influencing resolution in hydrogel bioprinting. 

Gelatin-Methacryloyl (GelMA) 

GelMA is a semi-synthetic hydrogel consisting of 
gelatin derivatized with methacrylamide and 
methacrylate groups. Sauty et al. (2022). experimented 
that GelMA hydrogels can be synthesized with a 
specific Degree of Functionalization (DoF) and 
adjusted to the intended application as a three- 
Dimensional (3D) cell culture platform and GelMa was 
also shown to support cartilage tissue formation using 
chondrocytes and MSCs (Sauty et al., 2022). Piao et al. 
(2021) found out that while dispensing cell-laden 
GelMa from a glass capillary significantly higher 
pressure was required; however, cell vitality and 
proliferation weren't significantly affected. 

Bio-printing neural tissues via DIW dictate some 
specific ink material requirements. More specifically, the 
elastic modulus (1.e., stiffness of the matrix of composite 
ink used) affects neural cell growth, vitality, and cell 
signaling. It has been found that brain tissues are 
compatible with a stiffness of 0.5 MPa approximately 
which is much less as compared to bone or cartilage 
tissues. Therefore, soft hydrogels need to exhibit low 
interfacial tension which allows cells to move across 
the tissue implant line. This can be achieved by a 
combination of two or more printing inks where one 
will possess the required biological property and the 
other with the task to regulate stiffness percentage 
(Mohd et al., 2022). 

Recent research suggests several approaches to 
combining nucleic acid delivery and bio-printing. One of 
them is developing gene-activated bioink. In this case, the 
nucleic acid of interest and its delivery mechanism could be 
incorporated in a single step by encapsulating it in a 
bio-printable material, resulting in a gene-activated 
bio-ink (Wu ef al., 2019). 

Inkjet Bioprinting 

Inkjet printing is a non-contact, controlled 3D printing 
process that allows for the dispersion of droplets with 
volumes ranging from 1-100 picoliters that include cell 
viability. Droplets are extruded from a nozzle in one of 
two ways: Drop by Drop (DOD) or Continuous Inkjet (CD 
(CIJ). DOD is the more suited of the two for tissue 
engineering. Furthermore, DOD can be classified into 
three types according to the depositing techniques. 

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DOI: 10.3844/ajeassp.2022.255.263 

Extrusion nozzle 

Moving platform 

Fig. 4: Direct ink writing schematic 

Inkjet 3D bio-printer 

Thermal _—_ Electromagnetic 

: : Piezoelectric Piezoelectric crystal 

Build platform 

Bio-ink __Bio-ink reservoir _ 

_Heater element _ element 

Fig. 5: Different Inkjet 3D bio-printer schematic 

Thermal (using heat to expand and deposit the material 
before the nozzle), electromagnetic and mechanical are 
considered some examples. Individual drops with 
diameters ranging from 25 to 50 um are generated 
according to predetermined requirements in DOD inkjet 
3D bio-printing. In CIJ 3D _ bio-printing continuous 
streams of individual droplets possessing a volume of 
100 um in diameter are ejected. It is found that as far 
as tissue engineering is concerned, electromagnetic and 
thermal inkjet printing has not been broadly adopted 
since these processes tend to affect the cell wall and its 
vitality after sonication at 15-25 Hz. That is the reason 
why thermal inkjet is more widely used for better cell 
vitality (Xiao et al., 2022; Yang et al., 2022; 
Aversa et al., 2021a-b; Aversa et al., 2022; Yang et al., 
2022). Multiple inkjets print heads consisting of 


several individual nozzles are being utilized to fasten the 
process. In the case of Thermal Inkjet Printing, ink is super- 
heated and bubbles are created which expand further until the 
ink is released through the nozzle. The heating temperature 
can reach up to 300°C for a few microseconds, thus, not 
affecting the viability of biologically printed DNA, cells, 
tissues, and other organs. Cell viability, in this case, has been 
found out approximately 85% (Tofan et al., 2022). Figure 5 
depicts different inkjet3D bio-printer schematics. 

In this technique, ink requirements dictate properties like 
desired viscosity and surface tension as viscosity affects 
clogging, and surface tension has an immense contribution 
to the shape of the drop not only after emerging from the 
nozzle but also on the substrate. The viscosity of the ink 
should be below 10 centipoises while surface tension should 
ideally range between 28-350 mn m! (Yang et al., 2022). 


3D Printing technology has greatly evolved in the past 
decade, with several different techniques being introduced in 
various fields and sectors. Available equipment now features 
reduced fabrication times as well as newly introduced 
materials, exhibiting a variety of properties. The introduction 
of 3D bio-printers utilizing bio-materials compatible with the 
human body offers an unprecedented ability to fabricate 
highly controlled porous interconnected structures that act as 
biological substrates for human cells to proliferate and lead 
to grown tissues. These structures must exhibit a variety of 
properties such as biocompatibility, bioresorbability as well 
as appropriate mechanical behavior. In this context, 
advanced biomaterials, like bio-inks acting as raw materials 
for 3D bio-printers, now offer the ability to produce high 
viability cell, tissue, and even direct DNA fabrication. The 
careful tuning of process parameters in the 3D bio-printer 
settings as well as the continuous introduction of new 
biomaterials possesses an unrivaled way to realize the full 
potential of this technology. 

Funding Information 
The authors have not received any financial support or 
funding to report. 


This article is original and contains unpublished 
material. The corresponding author confirms that all of the 
other authors have read and approved the manuscript and 
no ethical issues involved. 

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