Integrated Microfluidics Platforms for Investigating Injury and Regeneration of CNS Axons

Abstract

We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information. In this review, we introduced the recent advances to generate in vitro model system that is capable of mimicking the niche of CNS injury and regeneration and also of testing candidate drugs. We reconstructed the microenvironment of the regeneration of CNS neurons after injury to provide as in vivo like model system where the soluble and surface bounded inhibitors for regeneration are presented in physiologically relevant manner using microfluidics and surface patterning methods. The ability to control factors and also to monitor them using live cell imaging allowed us to develop quantitative assays that can be used to compare various drug candidates and also to understand the basic mechanism behind nerve regeneration after injury.

An in vitro spinal cord injury model to screen neuroregenerative materials

“…Two-dimensional reductionist tools in current widespread use e.g. microfluidic devices, have provided useful insights in tissue engineering, as these permit the study of fundamental, isolated aspects of neuronal regeneration and response to materials/biomolecules post-injury [43,44]. However, such in vitro models lack simulation of more complex multicellular pathology, within a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 relevant extracellular injury environment, for detailed readouts of the biological response to materials.…”

Monitoring the Differentiation and Migration Patterns of Neural Cells Derived from Human Embryonic Stem Cells Using a Microfluidic Culture System

“…Microfluidic devices were prepared as described previously (Kim et al, 2012). Briefly, we fabricated the chambers in polydimethylsiloxane (PDMS) using soft lithography and replica molding.…”

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

“…A few different approaches have been taken to mimic SCI pathology in vitro including: monoculture systems (primary and cell lines), co-culture systems, microfluidic devices and organotypic slice cultures [31][32][33][34][35][36][37]. A number of factors must be taken into consideration when evaluating the utility of each model system including the ability to mimic intercellular uptake dynamics, definition of cellular ratios to model specific CNS regions/disease states, standardisation of protein coronas around introduced nanoparticles, ease of nanoparticle delivery, and amenability to various (including real-time) imaging techniques [9].…”