{"title":"锂负载电纺纳米纤维支架促进大鼠模型中损伤坐骨神经的轴突再生和功能恢复","authors":"Banafsheh Dolatyar, Bahman Zeynali, Iman Shabani, Azita Parvaneh Tafreshi, Reza Karimi-Soflou","doi":"10.1007/s42242-024-00304-3","DOIUrl":null,"url":null,"abstract":"<p>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/<i>β</i>‐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/<i>β</i>-catenin target genes (<i>cyclinD1</i> and <i>c-Myc</i>) 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.</p><h3 data-test=\"abstract-sub-heading\">Graphic abstract</h3>\n","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds\",\"authors\":\"Banafsheh Dolatyar, Bahman Zeynali, Iman Shabani, Azita Parvaneh Tafreshi, Reza Karimi-Soflou\",\"doi\":\"10.1007/s42242-024-00304-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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/<i>β</i>‐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/<i>β</i>-catenin target genes (<i>cyclinD1</i> and <i>c-Myc</i>) 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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Graphic abstract</h3>\\n\",\"PeriodicalId\":48627,\"journal\":{\"name\":\"Bio-Design and Manufacturing\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.1000,\"publicationDate\":\"2024-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bio-Design and Manufacturing\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1007/s42242-024-00304-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bio-Design and Manufacturing","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s42242-024-00304-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds
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 (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/β-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.
期刊介绍:
Bio-Design and Manufacturing reports new research, new technology and new applications in the field of biomanufacturing, especially 3D bioprinting. Topics of Bio-Design and Manufacturing cover tissue engineering, regenerative medicine, mechanical devices from the perspectives of materials, biology, medicine and mechanical engineering, with a focus on manufacturing science and technology to fulfil the requirement of bio-design.