4.6 Article

Engineered axon tracts within tubular biohybrid scaffolds

Journal

JOURNAL OF NEURAL ENGINEERING
Volume 18, Issue 4, Pages -

Publisher

IOP PUBLISHING LTD
DOI: 10.1088/1741-2552/ac17d8

Keywords

axon tract; hyaluronic acid conduit; poly-lactic fibres; dorsal root ganglion cell culture; Schwann cell culture

Funding

  1. Spanish Ministry of Economy and Competitiveness through MINECO - AEI [RTI2018-095872-B-C21, C22/ERDF]
  2. Valencian Council for Innovation, Universities, Science and Digital Society [PROMETEO/2019/075]
  3. Spanish Cell Therapy Network [TerCel-RD16/0011/0026]
  4. Spanish Ministry of Education, Culture and Sports [FPU15/04975]

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This study utilizes a cells-biomaterials strategy to promote axon regeneration by combining a HA conduit filled with PLA fibers with pre-cultured SCs. The biohybrid mimics the directional features of axonal pathways in the nervous system, providing potential for strategies in the regeneration of axonal tracts.
Injuries to the nervous system that involve the disruption of axonal pathways are devastating to the individual and require specific tissue engineering strategies. Here we analyse a cells-biomaterials strategy to overcome the obstacles limiting axon regeneration in vivo, based on the combination of a hyaluronic acid (HA) single-channel tubular conduit filled with poly-L-lactide acid (PLA) fibres in its lumen, with pre-cultured Schwann cells (SCs) as cells supportive of axon extension. The HA conduit and PLA fibres sustain the proliferation of SC, which enhance axon growth acting as a feeder layer and growth factor pumps. The parallel unidirectional ensemble formed by PLA fibres and SC tries to recapitulate the directional features of axonal pathways in the nervous system. A dorsal root ganglion (DRG) explant is planted on one of the conduit's ends to follow axon outgrowth from the DRG. After a 21 d co-culture of the DRG + SC-seeded conduit ensemble, we analyse the axonal extension throughout the conduit by scanning, transmission electronic and confocal microscopy, in order to study the features of SC and the grown axons and their association. The separate effects of SC and PLA fibres on the axon growth are also experimentally addressed. The biohybrid thus produced may be considered a synthetic axonal pathway, and the results could be of use in strategies for the regeneration of axonal tracts.

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