Purpose <p>Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related mortality worldwide. Despite advances in detection and treatment, prognosis remains poor, with incidence projected to surpass one million cases annually by 2025. Current loco-regional therapies, such as surgical resection, radiofrequency ablation, and transarterial chemoembolization, are often limited by anatomical or clinical constraints, leaving many patients without viable options. This study aims to develop and experimentally characterize a synthetic liver phantom with tunable mechanical and permeability properties for preclinical testing and protocol optimization of injectable loco-regional therapies, including emerging alternatives such as YntraDose.</p> Methods <p>Porcine liver tissue was experimentally characterized to establish benchmark values for compression modulus and permeability. Based on these data, a 3D-printed phantom was designed using controlled microstructures to independently tune stiffness and permeability of parenchyma and tumor-mimicking regions. Compression testing, Darcy-based permeability experiments, and T2-weighted MRI were used for validation.</p> Results <p>The literature review revealed significant gaps in experimental permeability data, emphasizing the need for physical liver models to validate novel therapies. Preliminary design parameters were established for fabricating biomimetic liver phantoms with realistic mechanical and flow characteristics. Porcine liver permeability was measured in the order of 10⁻<sup>12</sup> m<sup>2</sup>, while the selected parenchyma-mimicking material exhibited a compression modulus of approximately 22&#xa0;kPa. Tumor-mimicking inclusions reached compression moduli of approximately 185&#xa0;kPa. Injection experiments demonstrated reproducible diffusion patterns, confirmed by mass balance and MRI visualization.</p> Conclusion <p>The proposed phantom provides a controlled experimental platform for investigating the mechanical and transport behavior of injectable agents in liver-mimicking tissue. While not intended for clinical or regulatory equivalence, this research-grade model bridges the gap between simplified in vitro systems and in vivo studies, supporting preclinical research and device development.</p>

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Development of a Synthetic Liver Phantom: Experimental Characterization of Tissue Mechanical Properties

  • Federica Potere,
  • Arianna Callera,
  • Emma Confortola,
  • Nada Khaled Mansour,
  • Simone Micalizzi,
  • Gianluca De Danieli,
  • Pieter Janssen,
  • Alice Crippa,
  • Paolo Oliva,
  • Francesco De Gaetano

摘要

Purpose

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related mortality worldwide. Despite advances in detection and treatment, prognosis remains poor, with incidence projected to surpass one million cases annually by 2025. Current loco-regional therapies, such as surgical resection, radiofrequency ablation, and transarterial chemoembolization, are often limited by anatomical or clinical constraints, leaving many patients without viable options. This study aims to develop and experimentally characterize a synthetic liver phantom with tunable mechanical and permeability properties for preclinical testing and protocol optimization of injectable loco-regional therapies, including emerging alternatives such as YntraDose.

Methods

Porcine liver tissue was experimentally characterized to establish benchmark values for compression modulus and permeability. Based on these data, a 3D-printed phantom was designed using controlled microstructures to independently tune stiffness and permeability of parenchyma and tumor-mimicking regions. Compression testing, Darcy-based permeability experiments, and T2-weighted MRI were used for validation.

Results

The literature review revealed significant gaps in experimental permeability data, emphasizing the need for physical liver models to validate novel therapies. Preliminary design parameters were established for fabricating biomimetic liver phantoms with realistic mechanical and flow characteristics. Porcine liver permeability was measured in the order of 10⁻12 m2, while the selected parenchyma-mimicking material exhibited a compression modulus of approximately 22 kPa. Tumor-mimicking inclusions reached compression moduli of approximately 185 kPa. Injection experiments demonstrated reproducible diffusion patterns, confirmed by mass balance and MRI visualization.

Conclusion

The proposed phantom provides a controlled experimental platform for investigating the mechanical and transport behavior of injectable agents in liver-mimicking tissue. While not intended for clinical or regulatory equivalence, this research-grade model bridges the gap between simplified in vitro systems and in vivo studies, supporting preclinical research and device development.