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Engineering Fiber-Based Nervous Tissue Constructs for Axon Regeneration.

Mevan L Siriwardane1, Kathleen Derosa1, George Collins1

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Nerve repair using biomaterial scaffolds shows promise. Fibers within 3D collagen hydrogels significantly enhance axon growth and guidance, with natural collagen fibers performing best for nerve regeneration.

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Axon outgrowth and regenerationCollagen fiberContact guidanceNerve regenerationTissue engineering

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Area of Science:

  • Biomaterials Science
  • Neuroscience
  • Tissue Engineering

Background:

  • Biomaterial scaffolds, including channels and 3D gels, have improved nerve repair models.
  • Autologous nerve grafts are the gold standard for severe nerve lesions (<20 mm), but biomaterial strategies often fall short.
  • Intraluminal nerve conduit fibers show promise for guiding regenerating axons.

Purpose of the Study:

  • To investigate how growing axons respond to fibers in a 3D environment.
  • To assess contact-guided axon growth using a construct of compliant collagen hydrogel and a fiber component.
  • To evaluate the influence of fiber stiffness and composition on axon regeneration.

Main Methods:

  • Utilized microfibers of poly-L-lactic acid (synthetic) and type I collagen (natural) with varying stiffnesses within a 3D collagen hydrogel.
  • Assessed preferential axon outgrowth, attachment, turning, and growth rates.
  • Examined the response of dorsal root ganglion neurons from adult rats to biomaterial fibers, including extracellular matrix (ECM) treatments.

Main Results:

  • Axons in the 3D hydrogel preferentially attached to, turned, and followed fibers, exceeding outgrowth in hydrogel alone.
  • Wet-spun type I collagen fibers from rat tail tendon demonstrated superior performance, promoting highly aligned and accelerated axon outgrowth.
  • Extracellular matrix treatments on fibers enhanced adult axon regeneration, highlighting the importance of both physical and biochemical properties.

Conclusions:

  • Fibers embedded in 3D hydrogels significantly enhance and guide axon regeneration compared to hydrogels alone.
  • The physical and biochemical properties of nerve conduit fibers are crucial for optimizing axon guidance and growth.
  • Natural collagen fibers, particularly wet-spun type I collagen, show great potential for improving nerve repair strategies.