Biodegradable hydrogels as scaffolds for nerve regeneration

Biodegradable hydrogels as scaffolds for nerve regeneration Valerio Magnaghi 1, Elisabetta Ranucci 2, Fabio Fenili 2, Patrizia Procacci 3, Giorgio Pivato 4, Paolo Cortese 4 and Paolo Ferruti 2 1 Department of Endocrinology, Physiopathology, Applied biology, Via Balzaretti 9, University of Milan, 20133 Milan, Italy 2 Department of Organic and Industrial Chemistry, University of Milan, Via Venezian 21, 20133 Milan, Italy 3 Department of Human Morphology and Biomedical Sciences - Citta' Studi, University of Milan, Via Mangiagalli 31, 20133 Milan, Italy 4 Hand Surgery Unit, IRCCS Multimedica, Via Milanese 300, 20099 Sesto San Giovanni, Italy Transected peripheral nerves are typically reconnected by direct end-to-end surgery or by autologous nerve graft. However, artificial synthetic guide are a successful alternative which may prevent neuroma formation (1). Among biodegradable conduits a novel approach is represented by use of tuneable polyamidoamine (PAA)-based hydrogels, with specific diameters, different shapes and/or dimensions. Depending by their crosslinking degree, hydrogels made by PAAs are tough material which may absorb large amounts of water. PAA hydrogels are biocompatible and biodegradable in vitro to non-toxic low molecular weight products over a period of time varying from few weeks to months (2). In order to evaluate their ability to promote nerve regeneration, PAA hydrogels scaled as scaffold conduits (10mm lenght, 1mm internal diameter) were studied by using an experimental model of rat nerve transection. A conduit was used to join a gap of 4-5 mm in the sciatic nerve, and a longitudinal analysis was made at 30, 45, 60, 90 days post-surgery. We performed the gait analysis to evaluate locomotor coordination, the plantar test to study nociception and pain sensitivity, and the morphological-morphometric analysis to evaluate the nerve recovery. Preliminary results indicate that nerve ends can be successfully joined by these PAA-based hydrogel conduits. One month after surgery, in fact, the regeneration is appreciable inside the conduit and the nerve is resistant to mechanical traction, without signs of inflammation or serum infiltrate. In the implanted rats 45 days after surgery the footprints analysis reveals a trail similar to sham-operated animals, while the thermal hypersensitivity tend to normalize to the control levels at later times. The morphological evaluation of the explanted conduit at 90 days after surgery shows normal myelin structures, confirming nerve regeneration and complete scaffold re-absorption. In conclusion, our results demonstrate that PAA hydrogels might be a promising scaffold tube for nerve regeneration. Further studies on the hydrogels functionalization for drug delivery, with growth factors or hormones, are in progress in our labs. References 1. Yannas, I.V., Hill, B.J., 2004. Selection of biomaterials for peripheral nerve regeneration using data from the nerve chamber model. Biomaterials 25, 1593-1600. 2. Jacchetti, E., Elimitri, E., Rodighiero, S., Indrieri, M., Gianfelice, A., Lenardi, C., Podest\ue0, A., Ranucci, E., Ferruti, P. Milani, P., 2008. P. Biomimetic poly(amidoamine) hydrogels as synthetic materials for cell culture. J. Biothecnol. 6, 1