Systemic and Local FK506 (Tacrolimus) and its Application in Peripheral Nerve Surgery

Kevin J Zuo; Tiam M Saffari; Katelyn Chan; Alexander Y Shin; Gregory H Borschel

doi:10.1016/j.jhsa.2020.03.018

Systemic and Local FK506 (Tacrolimus) and its Application in Peripheral Nerve Surgery

J Hand Surg Am. 2020 Aug;45(8):759-765. doi: 10.1016/j.jhsa.2020.03.018. Epub 2020 Apr 29.

Authors

Kevin J Zuo¹, Tiam M Saffari², Katelyn Chan³, Alexander Y Shin⁴, Gregory H Borschel⁵

Affiliations

¹ Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neurosciences and Mental Health, SickKids Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
² Division of Hand and Microvascular Surgery, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN.
³ Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neurosciences and Mental Health, SickKids Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, Department of Engineering, University of Toronto, Toronto, Ontario, Canada.
⁴ Division of Hand and Microvascular Surgery, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN. Electronic address: shin.alexander@mayo.edu.
⁵ Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neurosciences and Mental Health, SickKids Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, Department of Engineering, University of Toronto, Toronto, Ontario, Canada.

PMID: 32359866
DOI: 10.1016/j.jhsa.2020.03.018

Abstract

Peripheral nerve injuries (PNI) are common and frequently afflict otherwise healthy individuals after traumatic or iatrogenic events. Adjuvant therapies to improve functional outcomes after surgical repair of PNI have been investigated extensively in preclinical studies; however, to date, none have been clinically proven to have a notable therapeutic effect. FK506 (tacrolimus), a US Food and Drug Administration-approved systemic immunosuppressant, has demonstrated promising neuro-regenerative properties in both animal studies and clinical reports, but its adverse effects when systemically administered have precluded its broader applicability for patients with PNI. Recent advances in bioengineered drug delivery systems have made local FK506 delivery to a site of PNI an intriguing method of promoting peripheral nerve regeneration, with promising results in preclinical translational investigations. This review summarizes the preclinical and clinical evidence for FK506's beneficial effect in promoting peripheral nerve regeneration when administered systemically and locally.

Keywords: Drug delivery; FK506; nerve injury; nerve regeneration; regenerative medicine.

Publication types

Review

MeSH terms

Animals
Humans
Immunosuppressive Agents
Nerve Regeneration
Peripheral Nerve Injuries* / drug therapy
Peripheral Nerves
Sciatic Nerve
Tacrolimus*

Substances

Immunosuppressive Agents
Tacrolimus