Spermidine Crosslinked Gellan Gum-Based “Hydrogel Nanofibers” as Potential Tool for the Treatment of Nervous Tissue Injuries: A Formulation Study

Purpose: Aim of the work was to develop a potential neural scaffold, endowed with neuroprotective and neuroregenerative potential, to be applied at the site of nervous tissue injuries: nanofibers, consisting of gellan gum (GG), spermidine (SP) and gelatin (GL), were prepared via electrospinning. SP was selected for its neuroprotective activity and cationic nature that makes it an ideal GG cross-linking agent. GL was added to improve the scaffold bioactivity.

Methods: Mixtures, containing 1.5% w/w GG and increasing SP concentrations (0– 0.125% w/w), were prepared to investigate GG/SP interaction and, thus, to find the best mixture to be electrospun. Mixture rheological and mechanical properties were assessed. The addition of 0.1% w/w GL was also investigated. The most promising GG/SP/GL mixtures were added with poly(ethylene oxide) (PEO) and poloxamer (P407) and, then, electrospun. The resulting fibers were characterized in terms of size and mechanical properties and fiber morphology was observed after soaking in water for 24 hours. Nanofiber biocompatibility was assessed on Schwann cells.

Results: More and more structured GG/SP mixtures were obtained by increasing SP concentration, proving its cross-linking potential. After blending with PEO and P407, the mixture consisting of 1.5% w/w GG, 0.05% w/w SP and 0.1% w/w GL was electrospun. The resulting nanofibers appeared homogenous and characterized by a plastic behavior, suggesting a good mechanical resistance when applied at the injury site. Nanofibers were insoluble in aqueous media and able to form a thin gel layer after hydration. GG/SP/GL nanofibers showed a higher compatibility with Schwann cells than GG/SP ones.

Conclusion: SP and GL allowed the production of homogenous GG-based nanofibers, which preserved their structure after contact with aqueous media and showed a good compatibility with a neural cell line. After local application at the injury site, nanofibers should support and guide axonal outgrowth, releasing SP in a controlled manner.

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Materials

Deacetylated gellan gum (GG, Gelrite^®; Kelco Division of Merck & Co., Rahway, New Jersey, USA), spermidine trihydrochloride (SP; Sigma Aldrich, Milan, Italy), gelatin from porcine skin (GL, gel strength 90–110 g Bloom, Type A; Sigma Aldrich, Milan, Italy), poly(ethylene oxide) of high molecular weight (h-PEO, MW = 4000 kDa; Colorcon, Dartford, United Kingdom), poly(ethylene oxide) of low molecular weight (l-PEO, MW = 600 kDa; Sigma Aldrich, Milan, Italy) and Kolliphor P407 poloxamer (P407; Sigma Aldrich, Milan, Italy) were used for the preparation of the polymeric solutions to be electrospun.

Vigani B, Valentino C, Sandri G, Caramella CM, Ferrari F, Rossi S. Spermidine Crosslinked Gellan Gum-Based “Hydrogel Nanofibers” as Potential Tool for the Treatment of Nervous Tissue Injuries: A Formulation Study. Int J Nanomedicine. 2022;17:3421-3439
https://doi.org/10.2147/IJN.S368960