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

作　　者：Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel 

机构地区：[1]SickKids Research Institute,Neuroscience and Mental Health Program,Toronto,ON,Canada [2]Institute of Biomaterials and Biomedical Engineering,University of Toronto,Toronto,ON,Canada [3]Indiana University School of Medicine,Indianapolis,IN,USA [4]Division of Plastic and Reconstructive Surgery,the Hospital for Sick Children,Toronto,ON,Canada [5]Translational Biology and Engineering Program,Ted Rogers Centre for Heart Research,Institute of Biomedical Engineering,Faculty of Dentistry,University of Toronto,Toronto,ON,Canada

出　　处：《Neural Regeneration Research》2025年第1期291-304,共14页中国神经再生研究（英文版）

基　　金：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);a Kickstarter grant from the Institute of Biomedical Engineering(BME)at the University of Toronto(to KJWS);the Abe Frank Fund from the Riley’s Children Foundation(GHB)。

摘　　要：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.

关 键 词：BIODEGRADABLE local drug delivery nerve injury nerve regeneration nerve wrap TACROLIMUS 

分 类 号：R741[医药卫生—神经病学与精神病学]