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3D-printed Bolus in Radiotherapy
closer to the skin tissue. As a representative silicone, engineering, cell therapy, regenerative medicine, and
polydimethylsiloxane, which is colorless, odorless, stem cell and cancer research [31,32] . Synthetic hydrogels,
transparent and does not cause skin irritation, can be such as poly(vinyl alcohol), polyacrylamide (PAM), and
developed into commercial bolus . The polymer has PEG, generally possess precise controllable performance
[25]
excellent shear resistance, which can ensure its repeated use and show high mechanical properties, but lack biological
in radiotherapy. In addition, other silicone elastomers used moieties [33-35] . On the other hand, natural hydrogels, such
for processing boluses were also reported. For example, as chitosan, collagen, alginate, gelatin, and hyaluronic
a silicone elastomer based on dihydroxypolysioxane and acid (HA), have received wide attention due to their
ethyl polysilicate as the crosslinking agent was synthesized bioactive properties. However, their deficiencies include
to construct a bolus . Chiu et al. have constructed a uncontrollable degradation, potential immunogenicity,
[10]
silicone-based bolus through casting the liquid silicone and low mechanical properties [36-38] . Due to the distinct
(EcoFlex 00-30, Smooth-on Inc.) . Due to their chemical performance of each of the hydrogel classes, it can
[26]
stability, excellent biocompatibility, and good mechanical be selectively used in various fields according to the
properties, silicone elastomers have great advantages application requirements.
in preparing bolus, but their density (1.1 – 1.2 g/cm ) Among various materials, hydrogels have the best
3
being slightly different from the skin tissue may lead to tissue equivalence due to their similar density and structure
a decrease of tissue equivalence. No matter how good the to soft tissues. In recent years, hydrogel-based boluses
performance of the silicone elastomers, the sheet structure have been studied in the radiotherapy. For example, Kong
of bolus will always cause air gaps in the treatment of et al. fabricated a bolus composed of methacrylic acid
irregular surface of patients’ skin. hydrogel, which not only showed good dose parameters in
PU, also known as polycarbamate, is a kind of intensity modulated radiation therapy plans, but also had
polymer containing repeated structural units of -O-CO- a high degree of comfort and repeatability . Chiozzini
[10]
NH- bonds in its molecular chains. Due to its excellent et al. reported a hydrogel-based bolus consisting of the
biocompatibility and flexibility, PU has been widely used bacterial nanocellulose, which is made up of D-glucose
to construct medical devices, such as catheters, cardiac aid monomers and produced by several kinds of bacteria .
[27]
devices, medical films, artificial skin, and so on . PU- Compared to the commercial bolus, this bolus showed
[28]
based polymers can be developed by incorporating soft superiority in relation to the radiotherapy parameters,
segments (e.g. lactides, caprolactone, and poly(ethylene including the radiation attenuation potential and
glycol) [PEG]) or chain extenders in PU backbone. radiological density.
Recently, PU as a bolus material has entered the view of To the best of our knowledge, hydrogel has
researchers. For example, Zhao et al. have used a kind many advantages including flexibility, odorlessness,
of thermoplastic PU (TPU) to create a bolus for adjuvant nontoxicity, and high transparence, but up to now, it
treating a recurrent squamous cell carcinoma at the nasal has not been widely used as a bolus in clinical setting.
septum . Hou et al. have developed a PU-based bolus The reason is the quality of losing water easily and the
[15]
with multi-functions, including excellent mechanics nature of being fragile for the traditional hydrogel. Due
and adhesive properties, which make it fit closely to the to the high-water content (>85%), hydrogels tend to
patient’s skin with irregular surface . The mechanical lose water and undergo shrinkage or deformation, which
[7]
properties of PU can be tailor-made according to the greatly limits their application in radiotherapy. To solve
structure-property relationship. Therefore, PU is likely to this problem, a water-resisting layer, such as polyol
be processed into a bolus with good tissue equivalence. PU membrane or silicone oil, can be used to cover the
Besides, TangoPlus is another kind of commercial hydrogel surface to prevent dehydration of hydrogels .
[10]
elastomer used to print tissue-equivalent bolus . An alternate approach is to replace the water in the gel
[29]
with glycerine, maintaining the structure of hydrogels.
2.3.Hydrogel-based boluses used in radiotherapy In fact, the main problem limiting the wide
Hydrogel is a kind of 3D network consisting of application of traditional hydrogels is their poor
hydrophilic polymer chains, which are crosslinked mechanical behavior, including low stretchability, low
to matrix with high water content. Due to its excellent toughness, and notch-sensitiveness. For example, the
characteristics, including tunable physicochemical and alginate hydrogel is easily ruptured when just stretched to
bioactive properties, versatility in fabrication, high 1.2 times of its original length. Most traditional hydrogels
biocompatibility, and similarity to native extracellular with a fracture energy of about 10 J/m , are more
-2
matrix, the hydrogel has widely used as promising brittle than the cartilage with ~1000 J/m and natural
-2
biomaterials in the biomedical field . Up to now, different rubbers with 10,000 J/m . When the hydrogels contain
[30]
-2
hydrogels from both synthetic and natural hydrogels have notches, the strength and stretchability of samples can be
been developed in various applications, such as tissue markedly decreased. To solve this problem, various types
30 International Journal of Bioprinting (2021)–Volume 7, Issue 4