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High-Throughput Capable Three-Dimensional Tissue Model for Quantification of Electroporation Thresholds
Published on: August 19, 2025
Feasibility of Electroporation in Bone and in the Surrounding Clinically Relevant Structures: A Preclinical
Matilde Tschon1,2, Francesca Salamanna2, Mattia Ronchetti3
1Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy matilde.tschon@ior.it.
Abstract:
Skeletal metastases are a common cause of severe morbidity, reduction in quality of life and often early mortality. Consequently, improvements in therapies are necessary. Electroporation uses electric energy to alter cancer cell membrane permeability and enhance the local uptake of chemotherapeutics, thus leading to local tumor control. The aim of this study was to investigate the feasibility and safety of delivering electric field protocols causing electroporation of healthy bone and structures of clinical relevance using small and large animal models. Reversible electroporation was used in the rabbit sciatic nerve by applying 2 series of 8 pulses 100ms long at 1000 V/cm. Irreversible electroporation was used in rabbit distal femur condyles and in sheep vertebral body by applying 120 pulses 100ms long at 1750 V/cm. Any effect on surrounding sensitive structures was investigated. Reversible electroporation of sciatic nerve was associated with transient foot functional deficit that completely recovered at 30 days. Irreversible electroporation removed cells from trabeculae in the femurs of rabbits and in the vertebral body of sheep. After irreversible protocol, histology and microtomography demonstrated that the trabecular structure was maintained, the presence of new bone marrow cells, osteoblasts, and mineral apposition characterized by new trabeculae thinner than controls (P = .005) and a significant reduction in the ablated areas (-225%, P = .0219). Spinal cord, vertebral pedicles and spinal nerves showed transient edema in the absence of functional or structural alterations. Collectively, these results show that electroporation can be safely applied to bone even in the proximity of neuronal structures.
Insights
Electroporation safely ablates bone tumor cells in animal models. This cancer therapy preserves bone structure and surrounding nerves, showing promise for treating skeletal metastases with minimal side effects.
Area of Science:
- Oncology
- Biomedical Engineering
- Skeletal Biology
Background:
- Skeletal metastases significantly impact patient morbidity, quality of life, and survival.
- Electroporation enhances chemotherapeutic uptake for localized tumor control.
- Novel therapeutic strategies are crucial for managing bone metastases.
Purpose of the Study:
- To assess the feasibility and safety of electroporation in healthy bone and adjacent structures.
- To evaluate electroporation protocols in small (rabbit) and large (sheep) animal models.
Main Methods:
- Reversible electroporation applied to rabbit sciatic nerve (2x8 pulses, 100ms, 1000 V/cm).
- Irreversible electroporation applied to rabbit femur condyles and sheep vertebral bodies (120 pulses, 100ms, 1750 V/cm).
- Histology, microtomography, and functional assessments evaluated effects on bone and neural tissues.
Main Results:
- Reversible electroporation caused transient sciatic nerve deficits with full recovery within 30 days.
- Irreversible electroporation effectively eliminated cells within trabeculae, maintaining bone structure.
- Histology confirmed new bone marrow cells, osteoblasts, and mineral apposition with thinner trabeculae and reduced ablated areas.
- Neural structures (spinal cord, nerves) exhibited transient edema but no functional or structural damage.
Conclusions:
- Electroporation is a feasible and safe method for treating bone.
- The technique preserves bone architecture and surrounding neural tissues.
- Electroporation demonstrates potential as an adjuvant therapy for skeletal metastases.
