Development of nanostructured materials for peripheral nervous system (PNS) pathologies

Authors: Scaccini L, Battisti A, Gagliardi M, Del Grosso A, Cecchini M, Tonazzini I.

Peripheral neuropathies are a condition in which peripheral nerves are damaged. This condition affects millions of people every year worldwide and can be caused by external trauma, or by pathologies that impact peripheral nervous system components. Biocompatible scaffolds are emerging as an important tool to promote nerve regeneration in case of resection. However, when there is no physical damage of the nerve an effective drug delivery system is still lacking. To address these issues, we are working on two different approaches.

We have already demonstrated that nano/micro-grooved substrates are capable to direct neuronal and glial cell differentiation, polarization, and migration. We developed microstructured scaffolds, with specific directional topographies and tuneable stiffness, for peripheral nerve regeneration: our scaffolds, made of biodegradable and soft materials (compliant with nerve mechanics), were tested in vitro with neuronal and glial cell models.

Moreover, the restricted permeability of nerves, due to the presence of the blood-nerve barrier (BNB), makes difficult to transport drugs into their structure. Polymeric nanoparticles are under investigation for their ability to pass biological barriers (such as the blood-brain barrier). We developed polymeric nanoparticles (NPs) functionalized with peripheral nerve targeting molecules, procaine and a peptide, NP41.
We tested their biocompatibility and internalization capability in vitro in neural cell models. These nanoparticles can be further loaded with drugs of interest.

These two strategies can be either used as stand-alone systems or can be further combined to create innovative devices (e.g. scaffolds functionalized/enriched with NPs loaded with compounds of interest).
Such devices would be able to provide both a physical support for regeneration, and a controlled release of drugs for treating a wide variety of pathological conditions impacting PNS (e.g. nerve trauma, tumor resections, neurodegenerative disorders).