The nanotechnology-based strategy for the innervation of bioengineered teeth depicted here comprises: (i) a nanofibrous membrane as a structural scaffold mimicking the extracellular matrix (PCL) whose fibers are coated with cyclosporin A/PLGA nanoparticles; (ii) trigeminal ganglia for the intake of axons; and (iii) bioengineered teeth.
Scanning electron microscopy (a,b) and transmission electron microscopy (c,d) observation of the CsA-loaded PLGA nanoparticles and PCL scaffolds consisting of non-woven electrospun nanofibers (e) grafted with CsA-loaded PLGA nanoparticles after 3 layer-by-layer coatings (PLL/PLGA/CsA)3 (f) or 5 (PLL/PLGA/CsA)5 (f). Bars = 3 m in a and b, 200 nm in c, 50 nm in d, 1.5 m in e and 2.5 m in f and g. Reprinted from Kuchler-Bopp et al., Acta Biomaterialia (2017), doi: 10.1016/j.actbio.2017.01.001.Researchers have developed a nanostructured scaffold material impregnated with immunosuppressive drugs that encourages nerve regrowth in implanted replacement teeth [Kuchler-Bopp et al., Acta Biomaterialia (2017), doi: 10.1016/j.actbio.2017.01.001].
Most adults experience some dental decay within their lives and many end up losing teeth entirely. Implants currently used to replace missing teeth do not integrate with the surrounding tissue. Instead, bioengineered implants that promote the regrowth and regeneration of dental tissue and nerves would be ideal.
Now researchers from INSERM and the Université de Strasbourg inFrance together with CIBER de Bioingeniería, Biomateriales y Nanomedicinia and the University of Zaragoza in Spain have fabricated a nanostructured scaffold based on electrospun polycaprolactone (PCL) nanofibers. The nanofibers are embedded with poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with an immunosuppressive drug, cyclosporine A.
“[The] immunosuppressive drugs accelerate the innervation and vascularization of bioengineered teeth after only two weeks of implantation,” says lead researcher on the study Sabine Kuchler-Bopp. “[Our] bioengineered scaffold not only fulfils current limitations but also rapidly regenerates the tooth and innervates it, promoting its function.”
The scaffold is fabricated in a layer-by-layer manner, which allows the amount of drug-carrying nanoparticles deposited on the fibers to be precisely managed. Since the PLGA nanoparticles release the immunosuppressive drug in a controlled manner, the duration of drug release can be predetermined.
“The use of drug-eluting biodegradable nanoparticles decorating the surface of scaffolds allows a local action of the active principle with lower doses than the conventional systemic treatment and consequently decreases the risk of toxicity,” explains Kuchler-Bopp.
The inclusion of cyclosporine A appears to accelerate the innervation of transplanted tissue and bioengineered teeth.
“Our drug-eluting scaffold not only favors its integration but also promotes the recuperation of the teeth function and vascularization,” she says.
Furthermore, the materials used for the scaffold are biodegradable and have been approved by the US Food and Drug Administration (FDA) for medical products and devices. The researchers believe that such an active scaffold approach could be used in the treatment of bone defects to promote vascularization and innervation.
“Not only could immunosuppressive drugs be loaded in the scaffolds, but also morphogenetic proteins, growth factors, and so on for tailored drug release depending on the need,” points out Kuchler-Bopp.
Catherine Picart from Grenoble Institute of Technology believes that the approach is significant and novel in its use of cyclosporine A encourage tooth bud innervation. “This approach is simple and versatile, since other drugs may be loaded in the PLGA nanoparticles,” she says.
This article was originally published in Nano Today (2017), doi: 10.1016/j.nantod.2017.02.001