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Cancer Technologies

Cancer Technologies - Poster Session C

Poster H2 - Evaluating ethyl cellulose-ethanol gel formulation in a 3D in vitro model of cervical dysplasia

Friday, October 25, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Cervical cancer is the second leading cause of cancer-related death, disproportionately affecting women in low- and middle-income countries (LMICs)[1]. Women in LMICs have limited access to healthcare services, including the diagnosis and treatment of cervical dysplasia before it becomes cancer[1]. Current treatments for cervical dysplasia are costly and not conducive to mass-scale delivery in LMICs [2]. Ethanol ablation is a low-cost alternative treatment that we have enhanced with the addition of a polymer called ethyl cellulose (EC) to localize ethanol within target lesions and minimize leakage to surrounding tissue [3]. Previously we assessed how various delivery parameters (i.e. volume, injection rate, injection depth) impact the distribution volume of EC-ethanol in tissue mimicking agarose phantoms and in excised swine cervices; however, these models do not recapitulate the microenvironment of cervical dysplasia [3]. Thus, we developed a 3D in vitro model of cervical dysplasia using gelatin methacrylate (GelMA) [4]. Here we evaluated what concentration of GelMA and volumes of EC-ethanol led to optimal depot formation (i.e. the region that forms around the needle over the course of the injection).

Materials and

Methods:  First, we sought to understand the effect of GelMA concentration on EC-ethanol depot formation. 50 µL of 12% EC-ethanol (w/v) was injected into 4.5% and 8.7% GelMA-PBS (w/v) mixtures (concentrations were informed by previous studies [3],[4]). Because the GelMA is translucent and EC-ethanol forms a white gel when injected into aqueous media, the EC-ethanol depot volume can be easily visualized. Digital images were acquired of the constructs and depot areas were manually outlined in ImageJ. Second, we evaluated the impact of injection volume on depot volume. 50 µL or 120 µL of 12% EC-ethanol was injected into 4.5% GelMA constructs (n=5-7). ImageJ was used to trace the white EC-ethanol distribution and quantify the average area. A Wilcoxon Rank Sum test (non-parametric, two-tailed, alpha = 0.95) was performed in MATLAB to assess if there were statistical differences between the two groups.

Results, Conclusions, and Discussions: Representative images of the 4.5% and 8.7% GelMA constructs are shown in Figure 1A. As seen, the 4.5% GelMA construct produces a larger, more circular depot volume while the stiffer 8.7% GelMA produces a smaller, irregularly shaped depot. Representative images of 50 µL and 120 µL injections are shown in Figure 1B. While 120 µL produces a slightly larger depot, the difference is not significant (Figure 1C). Further, the 120 µL depots are more variable in size (as evidenced by the larger standard error in Figure 1C) and led to more backflow or leakage outside of the depot. Taken together, 50 µL EC-ethanol injections in 4.5% GelMA led to optimal depot formation. These results will guide future experiments in which cells will be added to constructs to study the zone of ablation induced by EC-ethanol injections.

Acknowledgements (Optional):  This study was funded by the Faculty Student Research Award through the University of Maryland.

References:
1. Ferlay et al, Int. J. Cancer. 2019, 144(8):1941-1953.
2. Allanson et al, Clin Obstet Gynecol. 2021, 64(3):501-518.
3. Adhikari et al, IEEE Trans Biomed Eng. 2024, 71(5):1488-1498.
4. Cadena et al, Frontiers in Biomaterials Science. 2024, 3:1-13.