Gellan Gum as a new biomaterial for Peripheral Nerve Regeneration

Peripheral nerve injuries (PNI) are a world-spread problematic that affects over one million people. For PNI that require surgical intervention and in the case of long gap injuries, autologous nerve grafts (ANG) have been considered the gold standard for decades. However, the use of ANG is accompanying by several drawbacks, for instance, donor site morbidity, limited availability and nerve mismatches, leading to merely 50% rates of success.

This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) for the engineering of a construct able to induce and promote peripheral nerve regeneration (PNR). More specifically, this approach pursues the development of GG systems as luminal fillers of nerve guides made from chitosan with a 5% degree of acetylation, thus adding guidance structures for regenerating axons. Four different GG formulations were produced, by combining varying amounts of High-Acyl GG (HA-GG) and methacrylated GG (MA-GG).

The hypothesis behind the application of GG systems is that they present varying degradation rates and add further guiding structures to the hollow chitosan tubes, for Schwann cells and axons support and migration.

The effective porosity of the freeze-dried networks was analysed by SEM and Micro-CT 3D reconstructions, while the degradation and swelling abilities were characterized in vitro for up to 30 days. The metabolic activity quantification of immortalized Schwann cells seeded onto the scaffolds was evaluated. To support these results, a qualitative viability assay was also performed. Finally, the developed constructs were freeze-dried within the chitosan nerve guides and implanted in a 10 mm rat sciatic nerve defect. Functional and histomorphological analyses after 3, 6, and 12 weeks in vivo, as well as extensive immunohistochemistry for nerve regeneration neovascularization revealed that the slow degrading  formulations could provide a basis for further development of GG scaffolds as luminal fillers for nerve guides.