Evaluation of Platinum-catalyzed Silicones for Fabrication of Biocompatible Patient-specific Elastic Bolus


 Purpose

We investigated the properties of platinum-catalyzed silicones with suitable characteristics for a biocompatible patient-specific elastic bolus.
Materials & Methods

We applied a platinum-catalyzed silicone (Ecoflex™ 0030) and a platinum cure liquid silicone (Dragon Skin™ 10 MEDIUM) to fabricate a biocompatible bolus using a mold and casting method with a 3D printer. We conducted physical evaluations including the shore hardness, cure time, transparency, and mixed viscosity. The dosimetric characteristics were basically investigated with surface dose and beam quality. For dosimetric evaluations using humanoid phantom, the dose differences between calculated dose and measured dose were compared with those of Dragon skin. To evaluate which boluses fit best, the volume of unwanted air gaps between the bolus and phantom was obtained from CT images. Biological evaluations were conducted on the skin sensitization, skin irritation, and cytotoxicity to ensure safe patient application.
Results

Ecoflex were biologically evaluated as safety materials. In addition, Ecoflex shows excellent physical properties with respect to a low shore hardness (00–30), short curing time (4 h), and low mixed viscosity (3,000). For the dosimetric properties using humanoid phantom, the average dose difference between the calculated dose and measured dose for Ecoflex is about 0.5% better than that of Dragon skin. In addition, a relatively smaller volume of unwanted air gaps for Ecoflex also showed than for Dragon skin, which these results tended to be the same as the dosimetric results.
Conclusion

The physical properties of Ecoflex including excellent adhesive strength, lower shore hardness reduces unwanted air gaps and ensures an accurate dose distribution. Therefore, it is a suitable material for fabricating biocompatible patient-specific elastic bolus. It would be an alternative to other materials of bolus and thus improve the efficiency for clinical use.

Introduction source software package that converts a structure file into stereolithography. The material used for the bolus mold was Z-high-impact polystyrene (Z-HIPS, Zortrax, Olsztyn, Poland), with a thickness of 1 mm. Once the mold fabrication was completed, the casting materials were poured into the mold. Dragon Skin and Ecoflex were used as the casting materials. Both materials were composed of an essential material (Part A) and a hardening agent (Part B).
Parts A and B were mixed at a 1:1 ratio and poured into the mold. The fabricated BPE boluses were then cured at room temperature (approximately 23℃) for the required curing time in a vacuum chamber of under 60 psi (4.1 atm) to remove air bubbles. The fabricated BPE boluses are shown in Figure 1.

Physical evaluations
Both Ecoflex and Dragon Skin are liquid silicone compounds. We designed 15 × 15 × 2 cm 3 cubic phantoms and determined the CT number through CT scanning. To evaluate the physical properties, the elongation at break, shore hardness, curing time, and tensile strength provided by the manufacturers were used. In addition, we prepared boluses of 3, 5 and 10 mm in thickness to measure the transparency for each bolus material. The transparency of each material was investigated through the measured absorbance within the visible region (400-800 nm) using the Eppendorf BioSpectrometer (Eppendorf, NY, USA). For each material, the effective atomic numbers (Zeff) were obtained from the elemental analysis results using x-ray fluorescence (XRF). Elements can be identified using their characteristic XRF emissions (voltage, 60 kV; current, 170 mA), and the intensity of x-ray fluorescence is proportional to the concentrations of elements in the samples. Moreover, the effective ratios of the atomic number and atomic mass (Z/A), as well as the mass density for each material, were calculated under the depth scaling factor of the BPE.

Biological evaluations
As medical devices, materials using a bolus material must comply with the ISO standards to ensure the patient safety. We conducted cytotoxicity tests for Ecoflex and Dragon Skin in accordance with ISO 10993-5, Part 5 (testing for in vitro cytotoxicity). All experiments were approved by the Institutional Animal Care and Use Committee in Seoul National University Hospital (SNUH-IACUC) and animals were maintained in the facility accredited AAALAC International in accordance with Guide for the Care and Use of Laboratory Animals 8th edition, NRC (2010). The tetrazolium-based colorimetric assay (MTT method) [12] was used for the experimental evaluations. According to ISO 10993-10 (test for irritation and skin sensitization), skin irritation and sensitization tests are also necessary biological examinations for evaluating medical devices. The results of these tests, provided in the material safety data sheets published by each manufacturer, were used as references in this study.

Dosimetric evaluations
To apply the evaluation of dosimetric properties, we measured the CT numbers for each bolus.   Figure 2 shows the picture of boluses with different thickness for average absorbance from 400 to 800 nm under normal room lighting conditions. Both materials tend to increase average absorbance as thickness increases. However, Ecoflex is more transparent, because it is lower in absorbance than the Dragon skin for the same thickness. With a thickness of 5 mm, Dragon skin is especially difficult to distinguish the surface.

Physical properties
The elemental compositions of these materials were obtained through XRF measurements.

Biological properties
For Ecoflex, the manufacturer carried out a different test and showed no effect in terms of delayed dermal contact sensitization (details available at www.smooth-on.com).
Consequently, like Dragon Skin, Ecoflex proved to be a biologically stable material suitable for fabricating boluses according to the skin sensitization, skin irritation, and cytotoxicity test results. Negative values with respect to the differences in dose indicate that unwanted air gaps underestimate the dose measurements. As shown in Figure 3 (b), the volume of unwanted air gaps between the bolus and surface of phantom was calculated based on CT images. The smallest air volume was observed in Ecoflex for all areas owing to the low shore hardness.

Dosimetric properties
This means that Ecoflex adhered closer to the surface of phantom as compared to the Dragon Skin bolus, as shown in Figure 4. In nose, neck and breast, the volume of unwanted airgap for Ecoflex and Dragon Skin were 10.9, 9.1, 49.7 cm 3 and 11.5, 14.9, 70.1 cm 3 , respectively.
These results tended to be the same as the dosimetric results.

Discussions
In this study, we evaluated the physical, biological, and dosimetric characteristics of boluses fabricated using Ecoflex and Dragon Skin. Both types of BPE bolus samples showed nontoxicity, good flexibility, and good durability, and could be easily fabricated. The M&C method using only a 3D printer is no longer the latest approach for fabricating BPE boluses.
Canters et al. fabricated a bolus using a 3D printed mold and filled it with silicone rubber [13]. Skin, which is a biologically stable material [12]. In addition to biological stability, Dragon Skin has desirable physical properties such as a low shore hardness and short curing time, which are beneficial for bolus fabrication. Dragon Skin was therefore proposed as a suitable bolus material. However, Dragon Skin has a relatively high mixed viscosity, which is a more significant disadvantage in the M&C method. When a bolus material with a high viscosity is cast in a thin mold (less than 5 mm in thickness), it becomes difficult to inject the material into deep parts of a mold. Ecoflex is a perfect solution to this problem. Because Ecoflex has a low viscosity, it can easily fill in curved parts of a mold, leaving no empty spaces.
Furthermore, compared to Dragon Skin, Ecoflex has a lower shore hardness and higher flexibility and is thus more suitable for attachment to irregular skin surfaces. The short curing time of Ecoflex also improves the efficiency of the bolus fabrication in terms of time. The results obtained thus far reveal that an Ecoflex BPE bolus material is a reasonable alternative to Dragon Skin and its physical properties alone can improve the efficiency of radiation therapy and BPE bolus fabrication; however, Ecoflex is not significantly more advantageous than Dragon Skin in terms of its biological and dosimetric properties. If a more suitable material for bolus fabrication is developed in the future, further studies will be necessary to evaluate the properties of this developed material as a replacement for Ecoflex.
Finally, a clinical quality assurance (QA) program needs to be considered as an essential step in fabricating 3D-printed BPE boluses, and such a QA program is necessary to ensure confidence when using such materials. Robar  The average difference in distance is less than 1 mm, the absolute difference is less than ±2 mm. As dosimetric characteristics still require additional verification, therefore, it will be performed in further studies.

Conclusion
We evaluated the physical, biological, and dosimetric properties of Ecoflex, a platinumcatalyzed silicone that can replace Dragon Skin. Because Ecoflex has a lower shore hardness and shorter curing time than Dragon Skin, it can improve the efficiency of both radiation therapy and bolus fabrication. In addition, clinical applicability of Ecoflex was verified by passing all biological tests. As a result, the bolus fabricated using Ecoflex was found to be the most effective and suitable from a clinical perspective. Furthermore, the excellent adhesive strength of Ecoflex reduces unwanted air gaps and ensures an accurate dose distribution.