4.7 Article

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

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2020.00497

Keywords

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

Funding

  1. Biological Sciences Research Council [315 BB/J001473/1]
  2. Wellcome Trust Principal Fellowship [212251_Z_18_Z]
  3. ERC [323113]
  4. European Commission NEUROTWIN grant [857562]
  5. Russian Science Foundation [19-75-10043]
  6. RFBR [19-32-60058]
  7. Russian Science Foundation [19-75-10043] Funding Source: Russian Science Foundation
  8. European Research Council (ERC) [323113] Funding Source: European Research Council (ERC)

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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.

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