NGF-loaded PLGA microparticles for advanced multifunctional regenerative electrodes.

ABSTRACT

Nerve guide conduits are currently the elective device for peripheral nerve reconstruction applications, as nerve autograft often is hampered by procedure invasiveness and limited nerve availability. Many technological improvements have been approached to enhance nerve regeneration driven by these devices, whose main drawbacks are often disordered sprouting and ineffective axon guidance. Among the adopted solutions to overcome these problems, embedding of extracellular matrix (ECM) proteins and neurotrophic factors (NF) in nerve conduits has been a promising one. Using free NFs, however suffers from different drawbacks mainly due to diffusion, degradation and local concentration boosting. As part of a wider EU-funded program for next gen regenerative electrodes, we developed NGF-loaded PLGA microparticles to use them immersed in a gel biomatrix that is being embedded in nerve conduits before implant, and allow for timed-controlled delivery instead of an initial concentration boost. Here we report the technological steps for the synthesis and initial testing with mouse dorsal root ganglia (DRG) explants, towards their full integration with a complex three-dimensional biomatrix into next-gen regeneration electrodes.