Abstract
Researchers are investigating the use of biomaterials with aligned guidance cues, like those provided by aligned electro spun fibers, to facilitate axonal growth across critical-length peripheral nerve defects. To enhance the regenerative outcomes further, these aligned fibers can be designed to provide local, sustained release of therapeutics. The drug fingolimod improved peripheral nerve regeneration in preclinical rodent models by stimulating a pro-regenerative Schwann cell phenotype and axonal growth. However, the systemic delivery of fingolimod for nerve repair can lead to adverse effects, so it is necessary to develop a means of providing sustained delivery of fingolimod local to the injury. Here we created aligned fingolimod-releasing electro spun fibers that provide directional guidance cues in combination with the local, sustained release of fingolimod to enhance neurite outgrowth and stimulate a pro-regenerative Schwann cell phenotype. Electro spun fiber scaffolds were created by blending fingolimod into poly (lactic-co-glycolic acid) (PLGA) at a w/w% (drug/polymer) of 0.0004, 0.02, or 0.04%. We examined the effectiveness of these scaffolds to stimulate neurite extension in vitro by measuring neurite outgrowth from whole and dissociated dorsal root ganglia (DRG). Subsequently, we characterized Schwann cell migration and gene expression in vitro. The results show that drug-loaded PLGA fibers released fingolimod for 28 days, which is the longest reported release of fingolimod from electro spun fibers. Furthermore, the 0.02% fingolimod-loaded fibers enhanced neurite outgrowth from whole and dissociated DRG neurons, increased Schwann cell migration, and reduced the Schwann cell expression of promyelinating factors. The in vitro findings show the potential of the aligned fingolimod-releasing electro spun fibers to enhance peripheral nerve regeneration and serve as a basis for future in vivo studies.
Recommended Citation
D. L. Puhl and J. L. Funnell and A. R. D'Amato and J. Bao and D. V. Zagorevski and Y. Pressman and D. Morone and A. E. Haggerty and M. Oudega and R. J. Gilbert, "Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors," Frontiers in Bioengineering and Biotechnology, vol. 8, article no. 937, Frontiers Media, Aug 2020.
The definitive version is available at https://doi.org/10.3389/fbioe.2020.00937
Department(s)
Chemical and Biochemical Engineering
Publication Status
Open Access
Keywords and Phrases
biomaterial; dorsal root ganglia; drug delivery; electrospun fibers; fingolimod hydrochloride; neurons; peripheral nervous system injury; Schwann cells
International Standard Serial Number (ISSN)
2296-4185
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
14 Aug 2020
Comments
National Institutes of Health, Grant NS092754