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International Journal of Bioprinting 3D bioprinting of boluses for radiotherapy

tissues [1,2] . When dealing with superficial lesions, it is speed, significantly hampering the manufacturing
necessary to use boluses with a suitable thickness, which efficiency of customized boluses [20,21] . On the other
are a class of materials applied on patients, to increase the hand, vat photopolymerization-based bioprinting can
skin dose and bolster therapeutic outcomes [3,4] . selectively solidify polymers directly from a liquid tank
Despite being widely used in clinical practice, while conducting the patterning and curing processes
[22]
commercial sheet boluses often fail to establish perfect skin simultaneously . As one of the photocurable 3D printing
contact in complex and irregular regions, resulting in the technologies, digital light process (DLP) has attracted wide
formation of air gaps between the bolus and skin . The attention on the grounds of its layer-by-layer molding
[5]
air gaps have a detrimental impact on the surface dose, method and rapid printing speed. Various medical devices
particularly in light of the growing utilization of advanced can be manufactured using DLP printing [1-3] . Therefore,
radiotherapy technologies, such as volume-modulated among various 3D bioprinting methods, the DLP
arc therapy (VMAT) and intensity-modulated radiation technique that utilizes layer photocuring appears to be the
therapy (IMRT) [6,7] . Therefore, to achieve better treatment most suitable technology for printing customized boluses.
outcome, customized boluses that can precisely conform to In recent years, natural polyphenols, such as tannic
any skin contour are urgently required. acid, gallate, and protocatechuic acid (PA), have gained
At present, various materials are known to have been increasing attention due to their ability to endow hydrogels
printed in the construction of customized boluses [3,8-11] . with anti-oxidative, anti-bacterial, and anti-inflammatory
Polylactic acid (PLA) and acrylonitrile butadiene styrene effects [23,24] . In this study, we incorporated PA into an
(ABS) are two commonly employed materials that can alginate (ALG) and acrylamide (AM) double network
be directly printed; however, their rigidity may cause (DN) using a glycerin/water solvent to create a composite
discomfort to patients with sensitive skin [12-14] . Silicone bioink for creating personalized multifunctional bolus. The
rubber is often used as a filling material by virtue of its designed bioink is compatible with DLP printing, which
excellent biocompatibility and chemical stability [15,16] ; offers faster building speed and higher manufacturing
however, it exhibits a density of 1.1–1.2 g/cm , which accuracy. Our constructed gel features a DN structure that
3
presents a density difference when compared to human exhibits excellent mechanical properties and has superior
tissue. Recently, Kong et al. have fabricated a bolus adhesion to the skin surface. Moreover, it is an organic
using hydrogel as the filling material . Although the gel that exhibits superior stability and anti-dehydration
[17]
structural and physical properties of hydrogels resemble properties. Given the excellent biocompatibility and
those of human soft tissue, several disadvantages have anti-bacterial properties it possesses, radiation-induced
deterred us from using hydrogels to prepare boluses. dermatitis can be mitigated to a certain extent. This
Firstly, the application of hydrogel to skin may leave a gap study presents an innovative preparation method for
between them. Secondly, the hydrogel is prone to water radiotherapy bolus and opens up new avenues for the
loss and deformation. Finally, reports have shown that application of multifunctional gels.
approximately 85% of cancer patients developed dermatitis
in hydrogel-exposed areas that are susceptible to bacterial 2. Materials and methods
infection [18,19] . This points to a critical shortcoming of the 2.1. Materials
hydrogels available on the current market, i.e., the lack
of anti-bacterial activity, which renders them ineffective The commercial bolus (Klarity, China) was utilized as
in preventing radiation dermatitis. Nevertheless, the control in this study. ALG, AM, PA, and polyethylene glycol
development of a bioink with superior properties such dimethacrylate (PEGDA, MW = 575) were procured from
as mechanical strength (excellent adhesiveness), anti- Shanghai MACKLIN Co., Ltd. Glycerol (GLY) was obtained
hydration, and biocompatibility remains a challenge. from Tianjin Fengchuan Chemical Reagent Technology
Co., Ltd. Live/Dead staining kit and cytoskeleton staining
In light of these challenges, three-dimensional (3D) kit were obtained from Invitrogen and Sigma, respectively.
bioprinting stands out as an important method for Lithium phenyl-2,4,6-trimethylbenzoylphosphinate
enhancing the properties of printed materials. A 3D (LAP) was provided by Jiangyin StemEasy. The chemicals
bioprinting approach appropriate for processing bolus employed in this experiment were of analytical grade and
must possess three crucial features, namely swift printing did not require further purification, while deionized water
speed, moderate printing size, and overall printing was utilized throughout the experiments.
precision. Extrusion and inkjet printing methods employ
a nozzle to dispense the polymers to the intended position 2.2. Preparation of gels
and then harden them through a curing process. However, To prepare the bioink, a solution consisting of water
the use of point-to-point printing leads to a slow printing and GLY was used to dissolve ALG and AM (20 wt%)

Volume 10 Issue 2 (2024) 251 doi: 10.36922/ijb.1589