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or how they produce their desired outputs. This lack of transparency makes these
algorithms unapproachable for clinical applications, which require deep trust in all
aspects of the system. Furthermore, there are legal, ethical, and regulatory rules that
need to be followed for deep learning detection systems to be used in clinical settings [45–48]. As a result, there is an emerging need for interpretable DL.These
methods allow end users to evaluate the usefulness and errors of ML/DL predictions
and diagnoses before taking action based on the advice [49].
P. Motie et al.
3.2 Generalizability
An algorithm can only have that high performance when tested with the fed data. If
you feed it new data, it will most likely not do as well as the training. In other words,
it is unrealistic to expect an algorithm designed for one set of questions to be helpful
for another set of questions that were not covered by the original research [50]. On
the other hand, most of the studies we’ve come across so far have been retrospective
and used previous data to train and test the newly designed algorithm, so we can’t
be sure that the model would be practical when facing the new emerging cases.
Although reported accuracy may seem enough to judge the efcacy of AI models,
their clinical applicability remains unclear [4].
3.3 Algorithmic Bias
The ndings show that there are three major sources of algorithmic bias: data bias,
method bias, and societal bias. For instance, a training dataset may not be adequate
or represent a random sample from the target population, thus resulting in either
sample inadequacy or sample selection bias [51].
3.4 Adaptation
This point refers to the amount of effort surgeons need to learn to work with a new
system or technology. As previously described, AI models are limited in the sense
that they don’t explain how their decisions were made. Essentially, these models are
considered black boxes, and there’s a high risk that they’ll become even more
obscure as they get better [4]. Adaptation to these newly developed AI-based systems might be time-consuming, especially for the previous generation that may
have gotten used to specic tools. However, new generations of dentists might be
considered digital natives who will naturally use digital tools.

Future Trends ofUsing Articial Intelligence inOral andMaxillofacial Surgery
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341
3.5 Ethical Issues
It is crucial to address the ethical concerns surrounding the use of AI, as it has the
potential to compromise privacy and security, violate condentiality and informed
consent, and undermine the independence of patients. AI in health care must be
more ethical; otherwise, it could lead to distrust among the public. Precision medicine is a sensitive topic due to the revelation of critical information such as patient’s
genomic data, drug intake, health status, metabolic status, and so on [52]; therefore,
it is of utmost importance to make sure that information security legislation and
policies are put into place to protect individuals, especially patients [14]. Using
patients’ medical records and data as part of an algorithm is another ethical concern.
In some cases, these datasets might be used to calibrate algorithms for commercialization, for which patients will need to pay again if they use them. However, despite
their importance, these indirect ethical dilemmas were not taken into account in
previous studies. To reach the sufcient data diversity for training a model with
accurate outcomes, AI should be developed in a way that is compatible with conserving social-cultural diversity and gender diversity without restricting lifestyle
choices or personal experiences [53].
AI can also be implemented in other parts of medical care, like devices and
robots (also called care bots) [54]. Surgeons have been increasingly relying on
robotic-assisted minimally invasive surgery in recent years. Thus, Larson etal. constructed principles that are based on a just culture1 to support an ethical framework
to minimize preventable harm for surgeons embracing new technology [55]. In the
same manner, Heyen and colleagues used the ve structural features of professionalized medicine as an analytical lens, to see how AI impacts the medical profession
[56]. In these mentioned principles, the surgeon interacts with the patient directly
and the AI is just a tool to help with the decision-making process. Responsibility
and the patient-clinician relationship are two critical considerations, so developing
and using AI should not be interpreted as diminishing human responsibility when
making decisions [53]. In addition, with the new revolution of robotic surgeons
doing all the tasks without the need for human presence, there should be new laws
concerning the ongoing debate about who should be responsible for the actions that
autonomous robots commit, keeping in mind that robots have no understanding of
blame, sanctions, accountability, liability, or culpability [57].
3.6 Cybersecurity Issues
There are also an increasing number of cybersecurity risks [57]. For example,
Bonaci etal. recently showed that there are cybersecurity risks in surgical robots
[58]. In order to prevent cyberattack, we should take steps to ensure that no software
is altered during surgery.
1
A model of workplace justice is designed to create fairness for providers and better outcomes for
patients. Just culture puts the emphasis from the error to the system design and behavioral choices.

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P. Motie et al.
3.7 Patients’ Rights andAutonomy
To get the best results from the treatment plan, the surgeon must consider the
patients’ biographical or demographic information. Issues like the patient’s personality, life situation, or cultural background can all affect the output. It’s crucial more
than ever to consider patients’ intentions while using AI tools in clinical practice. As
AI algorithms cannot take into account patient autonomy, it is essential for medical
practitioners to reect on their patient’s concerns carefully [56].
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P. Motie et al.

Application ofBioprinting Technology
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inOral andMaxillofacial Surgery
SadraMohaghegh andHaniehNokhbatolfoghahaei
1 Introduction
Additive manufacturing is one recently emerged technology used to fabricate predesigned porous scaffolds for maxillofacial bone regeneration [1, 2]. The aim is to
fabricate products that can mimic the macro and microstructural features of the
extracellular matrix [3–7]. In the conventional approach, cells are seeded on the
scaffolds after the printing phase to protect them from the thermal and chemical
stresses of the fabrication procedure [8]. However, this procedure does not provide
scaffolds with homogenized cell distribution, especially in depth [9]. Besides, a
limited number of cells can be seeded on the scaffolds considering their size.
Therefore, bioprinting technology has emerged to overcome the mentioned issues.
Bioprinting refers to additive manufacturing technology in which the scaffold is
fabricated from a blend of cells and biocompatible materials in a layer-by-layer
manner [10, 11]. The mentioned blend is called bio-ink [10]. Considering the biocompatibility of the printing procedure compared to traditional printing, biological
agents such as growth factors can be safely printed with the scaffold. Commonly
used bio-inks are made of synthetic and natural hydrogels such as gelatin, collagen,
alginate, chitosan, and tissue-specic decellularized extracellular matrix due to
their inherent capacity of providing a compatible, aqueous environment for cellular
activity [12].
Three main technologies have been reported for bioprinting of the scaffolds [1,
13] (Fig.1). In the extrusion-based method, the struts are formed from the material
S. Mohaghegh
Student Research Committee, School of Dentistry, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
H. Nokhbatolfoghahaei (*)
Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid
Beheshti University of Medical Sciences, Tehran, Iran
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. Khojasteh et al. (eds.), Emerging Technologies in Oral and Maxillofacial
Surgery, https://doi.org/10.1007/978-981-19-8602-4_17
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Inkjet Bioprinting Laser-assisted Bioprinting Extrusion Bioprinting
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S. Mohaghegh and H. Nokhbatolfoghahaei
Thermal
Heater
Fig. 1 Categorization of the commonly used bioprinting technologies [13]
Vapor
Bubble
Piezoelectric
Actuator
Laser Pulse
Energy-absorbing Layer
Pneumatic / Piston / Screw
Donor Layer
Bioink
extruded from a nozzle. The curable bio-ink is used to fabricate the scaffold laserbased method. Inkjet bioprinting refers to creating and fusing cell-laden droplets to
form the scaffold. Details of each technology and its advantages and disadvantages
are discussed in the current chapter.
2 Extrusion-Based Approach
In this approach, the bio-ink is extruded from a nozzle through pressure, piston, and
rotating screws. Screws are usually used in the case of printing high-viscosity materials [14]. However, screw-based extrusion can jeopardize cell viability signicantly
[15]. Although applying pressure is the most common approach, delay in the material extrusion in this method can decrease the printing resolution.
The material is extruded on a platform which can be stasis or have pre-dened
motion. The platform temperature is a signicant criterion that must be optimized in
the printing procedure [9]. For instance, considering that the stability of the uncrosslinked hydrogels is related to temperature, the nozzle temperature is set higher
to let material extrusion. In contrast, platform temperature is set to lower degrees to
cause material xation and strut formation [16].
Besides, the bed must provide adequate conditions for cell growth. Therefore,
Petri dishes and glass slides are suitable options for bed. More recently, direct tissue
bioprinting on the wound has been reported in patients suffering from burn wounds.
Indeed, the defect is considered as the bed in this instance [17].
Thermally induced gelation and cross-linkability are two main features of materials used for the extrusion bioprinting procedure [10, 18]. Hydrogels are the most
commonly used materials in this case. They have high water contact and lower
mechanical stability than polymers commonly used in the conventional printing
procedure. Therefore, pure hydrogels cannot be used for printing, and some modications are inevitable to optimize the material [18].
2.1 Optimizing Printing Materials
The rst approach to optimize the printing material is to improve mechanical features by adding more stable structures such as mineral materials (e.g.,

Application ofBioprinting Technology inOral andMaxillofacial Surgery
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hydroxyapatite (HA) [19], tricalcium phosphate (TCP) [6, 8, 20], and Bioglass
(BG) [21, 22]). Studies showed signicant improvements in the mechanical and
biological behavior of the ceramic-reinforced bio-printed hydrogels [8, 19, 20].
However, adding high amounts of ceramics can adversely impact the chemical
bonding of the hydrogel parts [23]. Besides, mineral particles can cause nozzle
plugging, and they may not homogenously distribute in the blend. Alongside the
mineral materials, more stable hydrogels such as alginate can be used to improve
the scaffold’s stability. More specically, alginate has been widely used combined
with gelatin [24, 25]. However, its main drawback is its slow invivo degradation
due to lack of alginate-degrading enzymes in the mammalian cells [26]. Besides,
they cannot provide the optimal surface for cell adhesion. Subsequently, alginate is
not a proper material to be used as the main component of the scaffold, and it has
been used as an additional part. Printing bio-ink in the liquid platform is another
method to increase the stability of the scaffolds during the fabrication [16, 27].
Chemical modication of the printing materials is the second approach to overcome the drawback of the pure hydrogels. Adding a methacrylate group is one of the
recommended methods. Gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (MeHA) are the commonly used materials in this concern [28]. Additional
parts can also be chemically modied to improve the function of the scaffold. Better
chemical bonding, higher biocompatibility, and enhanced mechanical properties
have been reported for oxidized alginate, called alginate dialdehyde (ADA) [29–
32]. It has to be mentioned that alginate can be irradiated to provide improved bio-
logical behavior [33].
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2.2 Cell Viability Improvements
Implanting scaffolds with higher cell density in the defect is one of the main advantages of bioprinting compared to the traditional approach. Besides, homogenous
cell distribution of bioprinting improves the scaffolds’ biological function specically in the marginal areas [34]. However, cells are exposed to further stress in the
bioprinting procedure, which necessitates customizing the printing set-up to
increase cell viability (Fig.2).
2.2.1 Printing Pressure andNozzle Geometry
It is apparent that increasing the pressure adversely affects cell viability [35].
Besides, the cell may survive in some instances while its function or phenotype is
altered [36]. Alongside the pressure, nozzle features can also impact cell viability.
The lower nozzle diameter and higher nozzle length can decrease cell viability
due to higher applied shear stress to the cells [37]. However, the nozzle width cannot be over-increased since it can impair the printing resolution. Nozzle shape can
also impact the applied shear stress to the cells. Choosing the optimal nozzle
shape is related to the printing pressure. Indeed, higher cell viability was reported
in conical- shaped nozzles in low-pressure printing (i.e., <300kPa), while there
was no difference between the conical and cylindrical nozzles in higher pressures [38].

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S. Mohaghegh and H. Nokhbatolfoghahaei
Cell Viability
in extrusion
bioprinting
Fig. 2 Factors that can impact the cell viability in the extrusion bioprinting procedure
Printing Pressure
Nozzle Diameter
Nozzle Shape
Nozzle Width
Fabrication Time
Extrusion Speed
Material Characteristics
2.2.2 Fabrication Time, Extrusion Speed,
andMaterial Characteristics
Cations must be taken to design the scaffolds in a manner that they can be printed in
a short time. Indeed, cells cannot tolerate the printing conditions for a long time
[12]. One way is to increase the printing speed. It has to be considered that printing
speed denes the imposed shear/compression stress to the cells, and it cannot be
increased carelessly. Decreasing the speed leads to material accumulation, which
increases the applied compression force to the cells [39]. On the other hand, higher
speeds lead to material stretching that increases shear stress to the cells [39]. Last
but not least, material features can impact cellular viability. Insufcient cellular
density and high blend viscosity increase the applied shear stress to the cells and
decrease their viability [37].
2.3 Crosslinking
Three main factors have to be considered in the crosslinking procedure [40]. First,
the material is used to crosslink the hydrogel. Indeed, a single type of hydrogel may
be crosslinked with various materials, leading to fabricating scaffolds with the same
material and different biological and physicochemical properties [28]. Second, the
time required to expose the material to the crosslinking agent is another factor. On
one side, the crosslinking procedure is performed more completely in the case of
exposing scaffolds to the agent for a longer time. However, this prolonged time can
adversely impact cell viability. Therefore, contrary to conventional printing, only
biocompatible agents can be applied as the crosslinking agent in bioprinting.
Third, the step in which crosslinking is performed is crucial. This procedure is
commonly performed after the bioprinting phase to increase its stability. In the other
approach, the material is crosslinked as it is extruded, as seen in the coaxial bioprinting [41]. This procedure is mainly used for vascular bioprinting in which the
crosslinking agent is extruded from the nozzle in the vessel’s core and the printing
material is extruded for the circular-shaped nozzle that surrounds the core nozzle.
Therefore, the tube-shaped struts are printed [42]. Preprinting crosslinking is the

Application ofBioprinting Technology inOral andMaxillofacial Surgery
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third approach that aims to increase the material stability during the printing procedure and decrease the concentration and duration of the post-fabrication crosslinking [6]. Over-crosslinking of the blend before printing can cause nozzle plugging.
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3 Laser-Based Stereolithography (SLA) Bioprinting
In this method, a photosensitive resin is polymerized in a layer-by-layer manner
based on the illumination pattern. Higher accuracy and printing resolution are
reported for SLA bioprinting than the extrusion-based method [43].
3.1 Material
Same as extrusion-based bioprinting, hydrogels are the chosen material for SLA
bioprinting. However, they must be modied to be crosslinked with UV or visible
light. Acryloyl or alkenyl functional groups are added to them for this purpose.
3.1.1 Photo-crosslinkable Polymer
Two groups of biomaterials are used in the SLA bioprinting [44]: First is photosensitive hydrogels with acryloyl groups such as poly(ethylene glycol) diacrylate
(PEGDA), PEGDMA, GelMA, and dextran methacrylate (DexMA). However, possible drawbacks of methacrylic groups on the cell surface may conne their application. Besides, demanding high amounts of free radicals for commencement of the
reaction and prolonged irradiation time are the other drawbacks of using methacrylic polymers for SLA bioprinting [45, 46]. The second group is photocrosslinkable gelatin which is the most commonly used biomaterial in SLA
bioprinting due to its optimal biological features [47].
Fast crosslinking systems have emerged to shorten the irradiation phase and
increase cell viability. Orthogonal UV crosslinking or thiol-ene chemistry is the
most commonly used approach in this case. This method is based on a chemical
reaction between thiol and alkene agents [48, 49]. Chemical products produced in
this approach are less toxic than the traditional method, and fewer free radicals are
required to start the reaction in this case [45, 50]. Applying the accelerated method
to fabricate modied gelatin scaffolds has been shown [51].
3.1.2 Non-photo-crosslinkable Polymers+Photoinitiators
Photoinitiators produce free radicals that crosslink the photosensitive hydrogels
[52]. Photoinitiator type denes the irradiation source (i.e., UV or visible light).
Considering the chemical reaction type, two types of photoinitiators exist [44]. Type
1 initiators (e.g., Irgacure 2959 and LAP) are the simpler ones that have faster
chemical reactions. LAP imitators can be activated through both UV and visible
light, and it has better biocompatibility and polymerization rate than Irgacure 2959
[53]. Type 2 initiators create the free radical through the cascade of reactions that
complicate and prolong the procedure.
Соседние файлы в папке @xirurgi_2025
