Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (1): 291-304.doi: 10.4103/NRR.NRR-D-22-01198

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Simeon C. Daeschler1, *, #, Katelyn J.W. So1, 2, #, Konstantin Feinberg1, 3, Marina Manoraj1, Jenny Cheung1, Jennifer Zhang1, 4, Kaveh Mirmoeini1, J. Paul Santerre5, Tessa Gordon1, 4, Gregory H. Borschel1, 2, 3, 4   

  1. 1SickKids Research Institute, Neuroscience and Mental Health Program, Toronto, ON, Canada; 2Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Division of Plastic and Reconstructive Surgery, the Hospital for Sick Children, Toronto, ON, Canada; 5Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Institute of Biomedical Engineering, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
  • Online:2025-01-15 Published:2025-01-15
  • Contact: Simeon C. Daeschler, MD, simeondaeschler@gmail.com.
  • Supported by:
    This work was supported by the German Research Foundation (DA 2255/1-1; to SCD); a SickKids Research Training Competition (RESTRACOMP) Graduate Scholarship (to KJWS), an Ontario Graduate Scholarship (to KJWS); a grant from Natural Sciences and Engineering Research Council of Canada (NSERC) (to KJWS) and a Kickstarter grant from the Institute of Biomedical Engineering (BME) at the University of Toronto (to KJWS); and the Abe Frank Fund from the Riley’s Children Foundation (GHB).

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Abstract: Axonal regeneration following surgical nerve repair is slow and often incomplete, resulting in poor functional recovery which sometimes contributes to lifelong disability. Currently, there are no FDA-approved therapies available to promote nerve regeneration. Tacrolimus accelerates axonal regeneration, but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery. The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site, with suitable properties for scalable production and clinical application, aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure. Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days. Size and drug loading are adjustable for applications in small and large caliber nerves, and the wrap degrades within 120 days into biocompatible byproducts. Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80% compared with systemic delivery. Given its surgical suitability and preclinical efficacy and safety, this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Key words: biodegradable, local drug delivery, nerve injury, nerve regeneration, nerve wrap, tacrolimus