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Research Article

Modeling the gene delivery process of the needle array-based tissue nanotransfection

Zhigang Li1,2,§Yi Xuan1,2,§( )Subhadip Ghatak1Poornachander R. Guda1Sashwati Roy1Chandan K. Sen1,2( )
Indiana Center for Regenerative Medicine and Engineering, Indiana University Health Comprehensive Wound Center, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Birck Nanotechnology Center and Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA

§ Zhigang Li and Yi Xuan contributed equally to this work.

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Graphical Abstract

Tissue nanotransfection is a novel biotechnology, and we employed a cell-arraybased model and a multilayer-stack-based model to simulate and illustrate the DNA delivery process across the skin tissue via the Si hollow needle array-based chip at nano and micro scales. It was found that a moderate electric field of about 150 V/mm can effectively deliver DNA with a balance between the delivery efficiency and safety concerns.

Abstract

Hollow needle array-based tissue nanotransfection (TNT) presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric pulses. In this work, the gene delivery process of TNT was simulated and experimentally validated. We adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin structure. The distribution of nonuniform electric field across the skin results in various electroporation behavior for each cell. Cells underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric field. The percentage of electroporated cells within the skin structure, with pore radius over 10 nm, increases from 25% to 82% as the applied voltage increases from 100 to 150 V/mm. Furthermore, the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based model. The delivery distance increased nonlinearly as the applied voltage and pulse number increased, which mainly depends on the diffusion characteristics and electric conductivity of each layer. It was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery depth. This work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings.

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Nano Research
Pages 3409-3421
Cite this article:
Li Z, Xuan Y, Ghatak S, et al. Modeling the gene delivery process of the needle array-based tissue nanotransfection. Nano Research, 2022, 15(4): 3409-3421. https://doi.org/10.1007/s12274-021-3947-1
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Received: 12 August 2021
Revised: 17 October 2021
Accepted: 24 October 2021
Published: 18 December 2021
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021
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