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Bioact Mater. 2021 Feb 22;6(9):2881-2893. doi: 10.1016/j.bioactmat.2021.02.016. eCollection 2021 Sep.

Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration: .

Bioactive materials

Ohan S Manoukian, Swetha Rudraiah, Michael R Arul, Jenna M Bartley, Jiana T Baker, Xiaojun Yu, Sangamesh G Kumbar

Affiliations

  1. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA.
  2. Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, USA.
  3. Department of Pharmaceutical Sciences, University of Saint Joseph, Hartford, CT, USA.
  4. Department of Immunology, Center on Aging, University of Connecticut Health, Farmington, CT, USA.
  5. Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA.

PMID: 33718669 PMCID: PMC7907220 DOI: 10.1016/j.bioactmat.2021.02.016

Abstract

Peripheral nerve injuries account for roughly 3% of all trauma patients with over 900,000 repair procedures annually in the US. Of all extremity peripheral nerve injuries, 51% require nerve repair with a transected gap. The current gold-standard treatment for peripheral nerve injuries, autograft repair, has several shortcomings. Engineered constructs are currently only suitable for short gaps or small diameter nerves. Here, we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine (4-AP) for peripheral nerve regeneration in a critical-size (15 mm) rat sciatic nerve transection model. The results of functional walking track analysis, morphometric evaluations of myelin development, and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls. Repaired nerves showed formation of thick myelin, presence of S100 and neurofilament markers, and promising functional recovery. The conduit's aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation, while the sustained release of 4-AP may increase nerve conduction, and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors. Overall, our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.

© 2021 [The Author/The Authors].

Keywords: Functional recovery; Nerve guidance conduit; Neurotrophic factor; Peripheral nerve regeneration; Sciatic nerve transection; Small-molecule drug delivery

Conflict of interest statement

There is No conflict of interest to publish this research article.

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