Hyaluronic acid/chitosan multilayer coatings on neuronal implants for localized delivery of siRNA nanoplexes.

Binding, stabilizing and promoting cellular uptake of siRNA are all critical efforts in creating matrices for the localized delivery of siRNA molecules to target cells. In this study, we describe the generation of chitosan imidazole/siRNA nanoplexes (NPs) embedded in nano scope polyelectrolyte multilayers (PEMs) composed of hyaluronic acid and chitosan for sustained and localized drug delivery. Regular PEM build-up, successful integration of NPs and controlled release under physiological conditions were shown.

Neuronal and glial responses to siRNA-coated nerve guide implants in vitro.

The manipulation of gene expression by RNA interference could play a key role in future neurotherapies, for example in the development of biohydrid implants to bridge nerve and spinal cord lesion gaps. Such resorbable biomaterial prostheses could serve as growth substrates together with specific siRNA to foster neuronal regeneration. To the best of our knowledge, we are the first to biofunctionalize neuronal prostheses with siRNA.

Chitosan/siRNA nanoparticles biofunctionalize nerve implants and enable neurite outgrowth.

Microstructured 20 μm thick polymer filaments used as nerve implants were loaded with chitosan/siRNA nanoparticles to promote nerve regeneration and ensure local delivery of nanotherapeutics. The stable nanoparticles were rapidly internalized by cells and did not affect cell viability. Target mRNA was successfully reduced by 65-75% and neurite outgrowth was enhanced even in an inhibitory environment.

Nerve fibroblast impact on Schwann cell behavior.

In order to reveal non-neuronal cell interactions after peripheral nerve lesions, we began to analyze the impact of sciatic nerve fibroblasts on Schwann cells in vitro. Both cell types are considered to have opposite effects on axonal regeneration. Few data are available on how repulsive nerve fibroblasts affect neuritotrophic Schwann cells and thus might indirectly influence axonal regrowth.