Polylactic Acid-Based Patterned Matrixes for Site-Specific Delivery of Neuropeptides On-Demand: Functional NGF Effects on Human Neuronal Cells

Olga A Sindeeva; Olga Kopach; Maxim A Kurochkin; Andrei Sapelkin; David J Gould; Dmitri A Rusakov; Gleb B Sukhorukov

doi:10.3389/fbioe.2020.00497

Polylactic Acid-Based Patterned Matrixes for Site-Specific Delivery of Neuropeptides On-Demand: Functional NGF Effects on Human Neuronal Cells

Front Bioeng Biotechnol. 2020 Jun 12:8:497. doi: 10.3389/fbioe.2020.00497. eCollection 2020.

Authors

Olga A Sindeeva^{1

2}, Olga Kopach³, Maxim A Kurochkin⁴, Andrei Sapelkin⁵, David J Gould⁶, Dmitri A Rusakov³, Gleb B Sukhorukov^{1

7

8}

Affiliations

¹ Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, Moscow, Russia.
² Remote Controlled Theranostic Systems Lab, Department of Nanotechnology, Educational and Research Institute of Nanostructures and Biosystems, Saratov State University, Saratov, Russia.
³ UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
⁴ Center for Photonics and Quantum Materials, Skolkovo Institute of Science and Technology, Moscow, Russia.
⁵ School of Physics and Astronomy, Queen Mary University of London, London, United Kingdom.
⁶ Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
⁷ School of Engineering and Material Science, Queen Mary University of London, London, United Kingdom.
⁸ Center of Biomedical Engineering, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Abstract

The patterned microchamber arrays based on biocompatible polymers are a versatile cargo delivery system for drug storage and site-/time-specific drug release on demand. However, functional evidence of their action on nerve cells, in particular their potential for enabling patterned neuronal morphogenesis, remains unclear. Recently, we have established that the polylactic acid (PLA)-based microchamber arrays are biocompatible with human cells of neuronal phenotype and provide safe loading for hydrophilic substances of low molecular weight, with successive site-specific cargo release on-demand to trigger local cell responses. Here, we load the nerve growth factor (NGF) inside microchambers and grow N2A cells on the surface of patterned microchamber arrays. We find that the neurite outgrowth in local N2A cells can be preferentially directed towards opened microchambers (upon-specific NGF release). These observations suggest the PLA-microchambers can be an efficient drug delivery system for the site-specific delivery of neuropeptides on-demand, potentially suitable for the migratory or axonal guidance of human nerve cells.

Keywords: NGF; drug delivery system; human N2A cells; patterned microchamber array; polylactic acid (PLA).

Grants and funding

WT_/Wellcome Trust/United Kingdom