Gellan Gum-based luminal fillers for peripheral nerve regeneration: anin vivostudy in the rat sciatic nerve repair model

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.

Detergent‐based decellularized peripheral nerve allografts: An in vivo preclinical study in the rat sciatic nerve injury model

“…Currently, tubulization is considered as a safe alternative to repair short defects in sensory nerves (Carriel, Alaminos, et al, 2014; Wangensteen & Kalliainen, 2010). Experimentally, promising results were obtained by the incorporation of intraluminal fillers to hollow NCs, such as fresh skeletal muscle (Crosio et al, 2019), gellan gum‐based hydrogels (Carvalho et al, 2018), acellular and cellular fibrin‐agarose hydrogels (Carriel et al, 2013; Carriel, Garzon, Campos, Cornelissen, & Alaminos, 2017), or functionalized collagen hydrogels (Gonzalez‐Perez et al, 2017). In addition, the use of novel biomimetic substitutes composed of collagen‐fibrin hydrogels (Schuh, Day, Redl, & Phillips, 2018), plastic compressed collagen scaffolds (Georgiou, Golding, Loughlin, Kingham, & Phillips, 2015), or nanostructured fibrin‐agarose hydrogels containing mesenchymal stem cells (Carriel et al, 2017; Chato‐Astrain et al, 2018) showed important improvements.…”

3D Printing and Bioprinting Nerve Conduits for Neural Tissue Engineering

“…This 3D scaffolds have good mechanical properties and have promising prospects in tissue engineering. Carvalho et al [77] prepared chitosan nerve conduit with acylated gellan gum as a lumen filler. The metabolic activity of Schwann cells seeded on the hydrogel increased, indicating that this conduit has the potential for neural tissue engineering.…”

Methylcobalamin‐Loaded PLCL Conduits Facilitate the Peripheral Nerve Regeneration

“…[ 2 ] Compared to the hollow lumen NGCs, the NGCs with fillers, multichannels, or cells and factors show better outcomes of nerve regeneration. [ 3–6 ] However, there are still some challenges such as the complicated preparation processes, the difficulty in maintaining cell viability and factor activity, and the mismatch of the size and mechanical property with the damaged nerves. [ 7 ]…”