Irreversible electroporation (IRE) is an emerging technology for non-thermal ablation of solid tumors. This study sought to integrate electrodes into microporous poly(caprolactone) (PCL) scaffolds previously shown to recruit metastasizing cancer cells in vivo in order to facilitate application of IRE to disseminating cancer cells. As the ideal parallel plate geometry would render much of the porous scaffold surface inaccessible to infiltrating cells, numerical modeling was utilized to predict the spatial profile of electric field strength within the scaffold for alternative electrode designs. Metal mesh electrodes with 0.35 mm aperture and 0.16 mm wire diameter established electric fields with similar spatial uniformity as the parallel plate geometry. Composite PCL-IRE scaffolds were fabricated by placing cylindrical porous PCL scaffolds between two PCL dip-coated stainless steel wire meshes. PCL-IRE scaffolds exhibited no difference in cell infiltration in vivo compared to PCL scaffolds. In addition, upon application of IRE in vivo, cells infiltrating the PCL-IRE scaffolds were successfully ablated, as determined by histological analysis 3 days post-treatment. The ability to establish homogeneous electric fields within a biomaterial that can recruit metastatic cancer cells, especially when combined with immunotherapy, may further advance IRE technology beyond solid tumors to the treatment of systemic cancer.
Bibliographical noteFunding Information:
This study was supported by the Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., NIH T32GM008347 (T.L.), the Kwanjeong Educational Foundation (H.R.L.), the Kuhrmeyer Chair in Mechanical Engineering (J.C.B.), Boston Scientific Corporation (Q.S. and P.R.), and the Institute for Engineering in Medicine Cancer Animal Core at the University of Minnesota. The authors would like to thank C. Daniel Frisbie for assistance analyzing biomaterial resistivity and Colleen Forster for histological training and assistance. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the National Science Foundation through the MRSEC program. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, United States, Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
© 2020, Biomedical Engineering Society.
- Cancer therapy
- Composite scaffold
- Irreversible electroporation
- Numerical modeling