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Local delivery of tacrolimus using electrospun poly-ε-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts

Roberton, Victoria H; Gregory, Holly N; Angkawinitwong, Ukrit; Mokrane, Omar; Boyd, Ashleigh S; Shipley, Rebecca J; Williams, Gareth R; (2023) Local delivery of tacrolimus using electrospun poly-ε-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts. Journal of Neural Engineering , 20 (1) , Article 016035. 10.1088/1741-2552/acad2a. Green open access

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Abstract

OBJECTIVE: Repair of nerve gap injuries can be achieved through nerve autografting, but this approach is restricted by limited tissue supply and donor site morbidity. The use of living nerve allografts would provide an abundant tissue source, improving outcomes following peripheral nerve injury. Currently this approach is not used due to the requirement for systemic immunosuppression, to prevent donor-derived cells within the transplanted nerve causing an immune response, which is associated with severe adverse effects. The aim of this study was to develop a method for delivering immunosuppression locally, then to test its effectiveness in reducing the immune response to transplanted tissue in a rat model of nerve allograft repair. APPROACH: A coaxial electrospinning approach was used to produce poly-ε-caprolactone fibre sheets loaded with the immunosuppressant tacrolimus. The material was characterised in terms of structure and tacrolimus release, then tested in vivo through implantation in a rat sciatic nerve allograft model with immunologically mismatched host and donor tissue. MAIN RESULTS: Following successful drug encapsulation, the fibre sheets showed nanofibrous structure and controlled release of tacrolimus over several weeks. Materials containing tacrolimus (and blank material controls) were implanted around the nerve graft at the time of allograft or autograft repair. The fibre sheets were well tolerated by the animals and tacrolimus release resulted in a significant reduction in lymphocyte infiltration at three weeks post-transplantation. SIGNIFICANCE: These findings demonstrate proof of concept for a novel nanofibrous biomaterial-based targeted drug delivery strategy for immunosuppression in peripheral nerve allografting.

Type: Article
Title: Local delivery of tacrolimus using electrospun poly-ε-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1088/1741-2552/acad2a
Publisher version: https://doi.org/10.1088/1741-2552%2Facad2a
Language: English
Additional information: Copyright © 2023 The Author(s). Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
Keywords: T-cell, allograft, biomaterials, electro-spinning, immunosuppression, tacrolimus, transplantation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10162524
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