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

Neural Regeneration Research 2025年第1期20卷 291-304页

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 SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** 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 *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** 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 *** 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

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Dual-functional porous and cisplatin-loaded polymethylmethacrylate cement for reconstruction of load-bearing bone defect kills bone tumor cells

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Bioactive Materials 2022年第9期7卷 120-130页

作者： Zhule Wang Liebert Parreiras Nogueira Håvard Jostein Haugen Ingrid CM.Van Der Geest Patricia Caetano de Almeida Rodrigues Dennis Janssen Thom Bitter Jeroen J.J.P.van den Beucken Sander CG.Leeuwenburgh Radboud University Medical Center Department of Dentistry-Regenerative BiomaterialsRadboud Institute for Molecular Life SciencesNijmegenthe Netherlands University of Oslo Department of BiomaterialsInstitute of Clinical DentistryFaculty of DentistryOsloNorway Radboud University Medical Center Department of OrthopedicsRadboud Institute for Health SciencesNijmegenthe Netherlands

Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft ***(PMMA)cement is the most commonly used bone substitute in clinical orthopedics in view of its ***,the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone ***,we introduce porosity into PMMA cement by adding carboxymethylcellulose(CMC)to facilitate such local delivery of chemotherapeutic drugs,while retaining sufficient mechanical properties for bone reconstruction in load-bearing *** results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC *** incorporation of≥3%CMC,the PMMA-based cements released up to 18%of the loaded cisplatin,in contrast to cements containing lower amounts of CMC which only released less than 2%of the cisplatin over 28 *** release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3%at day 7,which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based ***,tibias filled with PMMA-based cements containing up to 3%of CMC exhibit comparable compressive strengths as compared to intact *** conclusion,we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical *** such,these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.

关键词： Porous polymethylmethacrylate cement Bone tumor treatment local drug delivery Chemotherapeutic drug Ex vivo biomechanical assessment

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