Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve repair model

以结冷胶为基础的管腔填充剂用于周围神经再生:大鼠坐骨神经修复模型的体内研究

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作者:C R Carvalho, S Wrobel, C Meyer, C Brandenberger, I F Cengiz, R López-Cebral, J Silva-Correia, G Ronchi, R L Reis, C Grothe, J M Oliveira, K Haastert-Talini

Abstract

Peripheral nerve injuries (PNI) resulting in a gap to be bridged between the transected nerve ends are commonly reconstructed with autologous nerve tissue, but there is a need for valuable alternatives. This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels made from chitosan with a 5% degree of acetylation. The engineered constructs should remodel the structural support given to regenerating axons by the so-called bands of Büngner. Four different GG formulations were produced by combining varying amounts of High-Acyl GG (HA-GG) and Methacrylated GG (MA-GG). 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 and viability of immortalized Schwann cells seeded onto the freeze-dried networks were also evaluated. Finally, the developed hydrogel formulations 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 revealed that although it did not result in improved nerve regeneration, the NGC25:75 formulations could provide a basis for further development of GG scaffolds as luminal fillers for hollow nerve guidance channels.

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