Feasibility of Electroporation in Bone and in the Surrounding Clinically Relevant Structures: A Preclinical Investigation.
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.
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy matilde.tschon@ior.it.|Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
Matilde
M
Tschon
Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
Francesca
F
Salamanna
IGEA SpA, Carpi, Modena, Italy.
Mattia
M
Ronchetti
Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
Francesco
F
Cavani
Spine Surgery prevalently Oncologic and Degenerative, Rizzoli Orthopaedic Institute, Bologna, Italy.
Alessandro
A
Gasbarrini
Spine Surgery prevalently Oncologic and Degenerative, Rizzoli Orthopaedic Institute, Bologna, Italy.
Stefano
S
Boriani
Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.|Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department RIT Rizzoli, Rizzoli Orthopaedic Institute, Bologna, Italy.
Milena
M
Fini
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D018274:Electroporation / Q000379:methods*; D005260:Female; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D010006:Osteoblasts / Q000502:physiology; D011788:Quality of Life; D011817:Rabbits; D012756:Sheep
bone tissue; electroporation; nerve; spinal cord; tumor ablation treatment