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Evaluation of Ethyl Cellulose–Ethanol Ablation in a Human-Sized 3D Construct of High-Grade Cervical Dysplasia
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DOI：10.1002/jbm.a.70110.png)
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Abstract
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Current preclinical models for cervical dysplasia rely on animal systems that poorly mimic human anatomy. To address this and align with emerging initiatives to reduce animal experimentation, we developed a human-sized, 3D in vitro model of high-grade cervical dysplasia. The construct integrates normal human fibroblasts, keratinocytes, and SiHa cancer cells within a gelatin methacrylate (GelMA) hydrogel, engineered with a cervical “os” and asymmetric lesion to replicate native human cervical architecture. We utilized this platform to evaluate the efficacy and safety of ethyl cellulose–ethanol (EC–ethanol), a novel ablation therapy designed to mitigate the off-target leakage associated with traditional ethanol injections. While control injections of pure ethanol resulted in widespread, non-specific necrosis (approximately 99% cell death), EC–ethanol successfully formed a localized gel depot. High-resolution mapping of the ablation zone demonstrated that EC–ethanol significantly concentrated cytotoxicity within the dysplastic lesion while preserving surrounding healthy tissue. Margin analysis revealed a sharp therapeutic gradient, with cell death normalizing to background levels within approximately 2 mm of the injection site. These findings validate the translational potential of EC–ethanol as a spatially precise intervention and demonstrate the utility of macro-scale 3D models as powerful, ethical alternatives to animal testing for optimizing local drug delivery.
Keywords:
3D in vitro model
cervical dysplasia
ethanol ablation
ethyl cellulose
new approach methods
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