Biological performance of a novel biodegradable polyamidoamine hydrogel as a guide for peripheral nerve regeneration

Tissue engineering is a rapidly evolving discipline that seeks to repair, replace, or regenerate specific tissues or organs by translating fundamental knowledge in physics, chemistry and biology into practical and effective materials, devices, systems, and clinical strategies. Different polymeric biomaterials have been proposed as scaffold for tissue engineering applications. In recent years, special attention has been given to hydrogels. Hydrogels are insoluble and swellable materials that are widely used in the biomaterial field due to their biocompatibility, which derives from their high water absorption and surface properties. Several Agma1-based hydrogels obtained using ethylenediamine as cross-linker have been previously studied as scaffold for tissue engineering applications. They exhibited good results in term of biocompatibility and adhesion properties toward different cell lines. Unfortunately, their mechanical properties were not satisfactory in that their strength was still very low and they were very soft and breakable on handling. To overcome these problem, in this work a new synthetic method has been developed leading to hydrogels with similar composition and exhibiting the same biological properties but with improved mechanical strength . In particular a different two-step pathway has been followed. In the first step an acryloyl end-capped linear AGMA1 oligomer was synthesised using a controlled excess of the selected bisacrylamide; in the second step the oligomer was photopolymerized by UV irradiation producing hydrogels with the required mechanical properties. Using this new synthetic procedure, Agma1-UV made hydrogels with different form and shape were prepared. In particular, tubular scaffolds with 1 mm inner diameter were tested in vivo as conduit for nerve regeneration in a rat sciatic nerve cut model. The implant were analyzed at 30, 90 and 180 days post-surgery and resulted particularly promising in many important respects, such as biodegradability, biocompatibility, lack of inflammatory reaction upon degradation and capability of promoting optimum morphological and functional nerve regeneration. The regenerated nerves showed several interesting signs of morphological improvements even at 30 days post-surgery. At 180 day the scaffold was almost completely reabsorbed and the regenerated nerve morphologically comparable to the control animals.