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Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

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BIO-DESIGN AND MANUFACTURING 2024年第5期7卷 701-720页

作者： Dolatyar, Banafsheh zeynali, bahman Shabani, Iman Tafreshi, Azita Parvaneh Karimi-Soflou, Reza Univ Tehran Coll Sci Sch Biol Dev Biol Lab Tehran *** Iran Natl Inst Genet Engn & Biotechnol Fac Med Biotechnol Dept Mol Med Tehran *** Iran Amirkabir Univ Technol Tehran Polytech Dept Biomed Engn Tehran *** Iran

Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries (PNIs). While most studies have focused only on the topographical features of the grafts, we have considered both the biophysical and biochemical manipulations in our applied nanoscaffold. To achieve this, we fabricated an electrospun nanofibrous scaffold (ENS) containing polylactide nanofibers loaded with lithium (Li) ions, a Wnt/beta-catenin signaling activator. In addition, we seeded human adipose-derived mesenchymal stem cells (hADMSCs) onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was induced. We further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat model. Our results showed that Li-loaded ENSs gradually released Li within 11 d, at concentrations ranging from 0.02 to (3.64 +/- 0.10) mmol/L, and upregulated the expression of Wnt/beta-catenin target genes (cyclinD1 and c-Myc) as well as those of Schwann cell markers (growth-associated protein 43 (GAP43), S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and SRY-box transcription factor 10 (SOX10)) in differentiated hADMSCs. In the PNI rat model, implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured nerve. This improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs, which showed no fibrous connective tissue but enhanced organized myelinated axons. The potential of Li-loaded ENSs in promoting Schwann cell differentiation of hADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering. (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(si

关键词： Stem cell Schwann cell differentiation Electrospun nanofibrous scaffold Lithium ion Nerve regeneration CATENIN SIGNALING PATHWAY WNT/BETA-CATENIN STEM-CELLS POLYAMIDE FILMS DIFFERENTIATION REMYELINATION DEGENERATION INHIBITION EXPRESSION CHLORIDE

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Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

引用

Bio-Design and Manufacturing 2024年第05期 701-720页

作者： Banafsheh Dolatyar bahman zeynali Iman Shabani Azita Parvaneh Tafreshi Reza Karimi-Soflou Developmental Biology Laboratory School of BiologyCollege of Science University of Tehran Department of Biomedical Engineering Amirkabir University of Technology (Tehran Polytechnic) Department of Molecular Medicine Faculty of Medical Biotechnology National Institute of Genetic Engineering and Biotechnology

Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries(PNIs). While most studies have focused only on the topographical features of the grafts, we have considered both the biophysical and biochemical manipulations in our applied nanoscaffold. To achieve this, we fabricated an electrospun nanofibrous scaffold(ENS) containing polylactide nanofibers loaded with lithium(Li) ions, a Wnt/β-catenin signaling activator. In addition, we seeded human adipose-derived mesenchymal stem cells(h ADMSCs) onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was induced. We further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat model. Our results showed that Li-loaded ENSs gradually released Li within11 d, at concentrations ranging from 0.02 to(3.64 ± 0.10) mmol/L, and upregulated the expression of Wnt/β-catenin target genes(cyclin D1 and c-Myc) as well as those of Schwann cell markers(growth-associated protein 43(GAP43), S100 calcium binding protein B(S100B), glial fibrillary acidic protein(GFAP), and SRY-box transcription factor 10(SOX10)) in differentiated h ADMSCs. In the PNI rat model, implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured nerve. This improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs, which showed no fibrous connective tissue but enhanced organized myelinated axons. The potential of Li-loaded ENSs in promoting Schwann cell differentiation of h ADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering.

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