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.
Highlights
Micro- and nanostructured matrices have prompted new lines of study focusing on cell behavior and tissue engineering (Sousa et al, 2019)
microchamber array (MCA) could be composed of a variety of hydrophobic polymers, for instance, polylactic acid (PLA) (Zykova et al, 2019), poly(lactic-co-glycolic acid) (Sindeeva et al, 2018a), etc., with various inclusions inserted into the shell of microchambers, such as gold nanoparticles or the aggregates of carbon dots (Sindeeva et al, 2018b; 2019; Kurochkin et al, 2020)
We have demonstrated that PLA-based MCA are fully biocompatible with human cells of neuronal phenotype (Kopach et al, 2019)
Summary
Micro- and nanostructured matrices have prompted new lines of study focusing on cell behavior (adhesion, proliferation, morphology, alignment, migration, gene expression, and even differentiation) and tissue engineering (Sousa et al, 2019). Photolithography and electroplating techniques enable creation of templates with the choice of different geometries Such templates can be used either as independent matrices for growing cells, or as templates for the reusable synthesis of patterned films composed of polymers, proteins, and colloids, with nanoscale fidelity. A recently developed patterned microchamber array (MCA) (Kiryukhin et al, 2018) is, of particular importance: it provides a reservoir matrix consisting of microchambers (microcontainers). Such a matrix can be made of various synthetic and biocompatible polymers using the layerby-layer method (Ermakov et al, 2019). The release of a significant quantity of cargo can be induced by ultrasound as a result of the simultaneous opening of many microchambers (Sindeeva et al, 2018a), or otherwise individual chambers can be opened by optical laser targeting (Sindeeva et al, 2018b; Kopach et al, 2019; Kurochkin et al, 2020)
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