Promoting bioengineered tooth innervation using nanostructured and hybrid scaffolds.

The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth. This PCL scaffold, approved by the FDA and capable of mimicking the extracellular matrix, was obtained by electrospinning and decorated with CsA-loaded PLGA nanoparticles to allow a local sustained action of this immunosuppressive drug. Dental re-associations were co-implanted with a trigeminal ganglion on functionalized scaffolds containing PLGA and PLGA/cyclosporine in adult ICR mice during 2weeks. Histological analyses showed that the designed scaffolds did not alter the teeth development after in vivo implantation. The study of the innervation of the dental re-associations by indirect immunofluorescence and transmission electron microscopy (TEM), showed that 88.4% of the regenerated teeth were innervated when using the CsA-loaded PLGA scaffold. The development of active implants thus allows their potential use in the context of dental engineering. STATEMENT OF SIGNIFICANCE: Tooth innervation is essential for their function and protection and this can be promoted in vivo using polymeric scaffolds functionalized with immunosuppressive drug-loaded nanoparticles. Immunosuppressive therapy using biodegradable nanoparticles loaded with Cyclosporine A was found to accelerate the innervation of bioengineered teeth after two weeks of implantation.