{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:42:53Z","timestamp":1792813373488,"version":"4.5.0"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T00:00:00Z","timestamp":1430956800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100001677","name":"National institute of Health and Medical Research","doi-asserted-by":"publisher","award":["DP OD000798"],"award-info":[{"award-number":["DP OD000798"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Compared to the nerve guidance conduits (NGCs) constructed from a single layer of aligned nanofibers, bilayer NGCs with random and aligned nanofibers in the outer and inner layers are more robust and tear-resistant during surgical procedures thanks to an isotropic mechanical property provided by the random nanofibers. However, it remains unclear whether the random nanofibers will interfere with the aligned nanofibers to alter the extension pattern of the neurites and impede regeneration. To answer this question, we seeded dorsal root ganglia (DRG) on a double-layered scaffold, with aligned and random nanofibers on the top and bottom layers, respectively, and evaluated the outgrowth of neurites. The random nanofibers in the bottom layer exerted a negative impact on the extension of neurites projecting from the DRG, giving neurites a less ordered structure compared to those cultured on a single layer of aligned nanofibers. The negative impact of the random nanofibers could be effectively mitigated by preseeding the double-layered scaffold with Schwann cells. DRG cultured on top of such a scaffold exhibited a neurite outgrowth pattern similar to that for DRG cultured on a single layer of aligned nanofibers. We further fabricated bilayer NGCs from the double-layered scaffolds and tested their ability to facilitate nerve regeneration in a rat sciatic nerve injury model. Both histomorphometric analysis and functional characterization demonstrated that bilayer NGCs with an inner surface that was preseeded with Schwann cells could reach 54%, 64.2%, and 74.9% of the performance of isografts in terms of nerve fiber number, maximum isometric tetanic force, and mass of the extensor digitorum longus muscle, respectively. It can be concluded that the bilayer NGCs hold great potential in facilitating motor axon regeneration and functional motor recovery.<\/jats:p>","DOI":"10.1021\/am5018557","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T11:11:19Z","timestamp":1399461079000},"page":"9472-9480","source":"Crossref","is-referenced-by-count":160,"title":["Nerve Guidance\nConduits Based on Double-Layered Scaffolds of Electrospun Nanofibers\nfor Repairing the Peripheral Nervous System"],"prefix":"10.1021","volume":"6","author":[{"given":"Jingwei","family":"Xie","sequence":"first","affiliation":[{"name":"Washington University , , , ,","place":["St. Louis, Missouri, United States, 63130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"MacEwan","sequence":"additional","affiliation":[{"name":"Washington University , , , ,","place":["St. Louis, Missouri, United States, 63130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Liu","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya","family":"Jesuraj","sequence":"additional","affiliation":[{"name":"Washington University , , , ,","place":["St. Louis, Missouri, United States, 63130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Li","sequence":"additional","affiliation":[{"name":"Washington University , , , ,","place":["St. Louis, Missouri, United States, 63130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hunter","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine , , , ,","place":["St. Louis, Missouri, United States, 63110"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younan","family":"Xia","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]},{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,7]]},"reference":[{"key":"2026090211384276300_cit1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3171\/foc.2004.16.5.2","article-title":"Pathophysiology of Peripheral Nerve Injury: A Brief\nReview","volume":"16","author":"Burnett","year":"2004","journal-title":"Neurosurg. Focus"},{"key":"2026090211384276300_cit2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/00005373-199807000-00025","article-title":"Analysis of Upper and\nLower Extremity Peripheral Nerve Injuries in a Population of Patients\nwith Multiple Injuries","volume":"45","author":"Noble","year":"1998","journal-title":"J. Trauma Acute Care\nSurg."},{"key":"2026090211384276300_cit3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.bioeng.5.011303.120731","article-title":"Neural\nTissue Engineering: Strategies for Repair and Regeneration","volume":"5","author":"Schmidt","year":"2003","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"2026090211384276300_cit4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1098\/rsif.2011.0438","article-title":"A Biomaterials Approach\nto Peripheral Nerve Regeneration: Bridging the Peripheral Nerve Gap\nand Enhancing Functional Recovery","volume":"9","author":"Daly","year":"2012","journal-title":"J. R. Soc.,\nInterface"},{"key":"2026090211384276300_cit5","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/1098-2388(200010\/11)19:3<312::AID-SSU13>3.0.CO;2-M","article-title":"Challenges to Nerve\nRegeneration","volume":"19","author":"Evans","year":"2000","journal-title":"Semin. Surg. Oncol."},{"key":"2026090211384276300_cit6","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1001\/archotol.124.10.1081","article-title":"Tissue\u2013Engineered\nConduit for Peripheral Nerve Repair","volume":"124","author":"Hadlock","year":"1998","journal-title":"Arch. Otolaryngol.,\nHead Neck Surg."},{"key":"2026090211384276300_cit7","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1016\/j.biomaterials.2006.02.030","article-title":"Peripheral\nNerve Regeneration: An Opinion on Channels, Scaffolds and Anisotropy","volume":"27","author":"Bellamkonda","year":"2006","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit8","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/00006534-199003000-00015","article-title":"Clinical Nerve Reconstruction with a Bioabsorbable\nPolyglycolic Acid Tube","volume":"85","author":"Mackinnon","year":"1990","journal-title":"Plast. Reconstr. Surg."},{"key":"2026090211384276300_cit9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/adhm.201100021","article-title":"Electrospun Nanofibers for Regenerative Medicine","volume":"1","author":"Liu","year":"2012","journal-title":"Adv. Healthcare Mater."},{"key":"2026090211384276300_cit10","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1006\/exnr.1999.7315","article-title":"Nerve Guides Seeded\nwith Autologous Schwann Cells Improve Nerve Regeneration","volume":"161","author":"Rodri\u0301guez","year":"2000","journal-title":"Exp. Neurol."},{"key":"2026090211384276300_cit11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1039\/B9NR00243J","article-title":"Electrospun Nanofibers for Neural\nTissue Engineering","volume":"2","author":"Xie","year":"2010","journal-title":"Nanoscale"},{"key":"2026090211384276300_cit12","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1016\/j.biomaterials.2004.06.051","article-title":"Electrospinning of Nano\/Micro Scale Poly (L\u2013lactic\nacid) Aligned Fibers and Their Potential in Neural Tissue Engineering","volume":"26","author":"Yang","year":"2005","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit13","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1089\/ten.2006.12.1197","article-title":"Electrospinning of Polymeric Nanofibers\nfor Tissue Engineering Applications: A Review","volume":"12","author":"Pham","year":"2006","journal-title":"Tissue Eng."},{"key":"2026090211384276300_cit14","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/adma.200400719","article-title":"Electrospinning of\nNanofibers: Reinventing the Wheel?","volume":"16","author":"Li","year":"2004","journal-title":"Adv. Mater."},{"key":"2026090211384276300_cit15","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1111\/j.1551-2916.2006.00989.x","article-title":"Electrospinning: A Simple and Versatile Technique for\nProducing Ceramic Nanofibers and Nanotubes","volume":"89","author":"Li","year":"2006","journal-title":"J. Am. Ceram. Soc."},{"key":"2026090211384276300_cit16","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1021\/nl0344256","article-title":"Electrospinning of Polymeric and Ceramic Nanofibers as Uniaxially\nAligned Arrays","volume":"3","author":"Li","year":"2003","journal-title":"Nano Lett."},{"key":"2026090211384276300_cit17","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1021\/nl0504235","article-title":"Collecting Electrospun\nNanofibers with Patterned Electrodes","volume":"5","author":"Li","year":"2005","journal-title":"Nano Lett."},{"key":"2026090211384276300_cit18","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/pat.1839","article-title":"Ceramic Nanofibers Fabricated by Electrospinning and\nTheir Applications in Catalysis, Environmental Science, and Energy\nTechnology","volume":"22","author":"Dai","year":"2011","journal-title":"Polym. Adv. Technol."},{"key":"2026090211384276300_cit19","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/adma.200306226","article-title":"Electrospinning\nNanofibers as Uniaxially Aligned Arrays and Layer\u2013by\u2013Layer\nStacked Films","volume":"16","author":"Li","year":"2004","journal-title":"Adv. Mater."},{"key":"2026090211384276300_cit20","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1021\/nn900070z","article-title":"Neurite Outgrowth on Nanofiber Scaffolds with Different Orders, Structures,\nand Surface Properties","volume":"3","author":"Xie","year":"2009","journal-title":"ACS Nano"},{"key":"2026090211384276300_cit21","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1002\/adfm.200801904","article-title":"Conductive Core\u2013Sheath\nNanofibers and Their Potential Application in Neural Tissue Engineering","volume":"19","author":"Xie","year":"2009","journal-title":"Adv. Funct. Mater."},{"key":"2026090211384276300_cit22","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.biomaterials.2008.09.046","article-title":"The Differentiation of Embryonic Stem Cells Seeded on Electrospun\nNanofibers into Neural Lineages","volume":"30","author":"Xie","year":"2009","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit23","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jneumeth.2007.06.018","article-title":"Binary Imaging Analysis for Comprehensive\nQuantitative Histomorphometry of Peripheral Nerve","volume":"166","author":"Hunter","year":"2007","journal-title":"J. Neurosci. Methods"},{"key":"2026090211384276300_cit24","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/jemt.10296","article-title":"Intracllular\nand Extracellular Roles of S100 Proteins","volume":"60","author":"Donato","year":"2003","journal-title":"Microsc.\nRes. Technol."},{"key":"2026090211384276300_cit25","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/neu.480230410","article-title":"S100 is Present in Developing Chicken Neurons and Schwann\nCell and Promotes Motor Neuron Survival in vivo","volume":"23","author":"Bhattacharyya","year":"1992","journal-title":"J. Neurobiol."},{"key":"2026090211384276300_cit26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/ajcp\/79.1.37","article-title":"An Immunoperoxidase Investigation\nof S\u2013100 Protein in Granular Cell Myoblastomas: Evidence for\nSchwann Cell Derivation","volume":"1","author":"Armin","year":"1983","journal-title":"Am. J. Clin. Pathol."},{"key":"2026090211384276300_cit27","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/jbm.a.31285","article-title":"Aligned\nElectrospun Nanofibers Specify the Direction of Dorsal Root Ganglia\nNeurite Growth","volume":"83","author":"Corey","year":"2007","journal-title":"J. Biomed. Mater. Res., Part\nA"},{"key":"2026090211384276300_cit28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.actbio.2010.08.004","article-title":"Two Pole Air Gap\nElectrospinning: Fabrication of Highly Aligned, Three\u2013Dimensional\nScaffolds for Nerve Reconstruction","volume":"7","author":"Jha","year":"2011","journal-title":"Acta Biomater."},{"key":"2026090211384276300_cit29","doi-asserted-by":"crossref","first-page":"016001","DOI":"10.1088\/1741-2560\/6\/1\/016001","article-title":"Creation\nof Highly Aligned Electrospun Poly\u2013L\u2013lactic Acid Fibers\nfor Nerve Regeneration Applications","volume":"6","author":"Wang","year":"2009","journal-title":"J. Neural\nEng."},{"key":"2026090211384276300_cit30","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1021\/nl071182z","article-title":"Bioactive Nanofibers: Synergistic Effects of Nanotopography and Chemical\nSignaling on Cell Guidance","volume":"7","author":"Patel","year":"2007","journal-title":"Nano Lett."},{"key":"2026090211384276300_cit31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10439-005-9013-4","article-title":"Neurite Outgrowth\nis Directed by Schwann Cell Alignment in the Absence of Other Guidance\nCues","volume":"34","author":"Thompson","year":"2006","journal-title":"Annu. Biomed. Eng."},{"key":"2026090211384276300_cit32","doi-asserted-by":"crossref","first-page":"28208","DOI":"10.1074\/jbc.M003922200","article-title":"Schwann Cells Synthesize Type V Collagen That Contains\na Novel Alpha4 Chain: Molecular Cloning, Biochemical Characterization\nand High Affinity Heparin Binding of Alpha4 (V) Collagen","volume":"275","author":"Chernousov","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026090211384276300_cit33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1750-3639.1999.tb00229.x","article-title":"Nerve Injury, Axonal Degeneration and Neural Regeneration:\nBasic Insights","volume":"9","author":"Stoll","year":"1999","journal-title":"Brain Pathol."},{"key":"2026090211384276300_cit34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1006\/exnr.1998.6955","article-title":"Collagen\u2013GAG Substrate Enhances\nthe Quality of Nerve Regeneration Through Collagen Tubes up to Level\nof Autograft","volume":"154","author":"Chamberlain","year":"1998","journal-title":"Exp. Neurol."},{"key":"2026090211384276300_cit35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1089\/107632701753337663","article-title":"Micropatterned\nSchwann Cell\u2013Seeded Biodegradable Polymer Substrates Significantly\nEnhance Neurite Alignment and Outgrowth","volume":"7","author":"Miller","year":"2001","journal-title":"Tissue\nEng."},{"key":"2026090211384276300_cit36","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.biomaterials.2004.04.046","article-title":"Micropatterned\nPolymer Substrates Control Alignment of Proliferating Schwann Cells\nto Direct Neuronal Regeneration","volume":"26","author":"Schmalenberg","year":"2005","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit37","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1016\/j.actbio.2009.12.038","article-title":"The Use of Air Plasma in Surface Modification of Peripheral\nNerve Conduits","volume":"6","author":"Ni","year":"2010","journal-title":"Acta Biomater."},{"key":"2026090211384276300_cit38","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0142-9612(00)00278-7","article-title":"Oriented Schwann Cell Growth on Micropatterned\nBiodegradable Polymer Substrates","volume":"22","author":"Miller","year":"2001","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit39","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1016\/j.actbio.2009.01.039","article-title":"Aligned and Random Nanofibrous Substrate for the in vitro Culture of Schwann Cells for Neural Tissue Engineering","volume":"5","author":"Gupta","year":"2009","journal-title":"Acta Biomater."},{"key":"2026090211384276300_cit40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.biomaterials.2008.09.017","article-title":"In vitro Cell Alignment\nObtained with a Schwann Cell Enriched Microstructured Nerve Guide\nwith Longitudinal Guidance Channels","volume":"30","author":"Bozkurt","year":"2009","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit41","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/(SICI)1097-0169(1999)42:4<331::AID-CM6>3.0.CO;2-7","article-title":"Adhesion, Alignment,\nand Migration of Cultured Schwann Cells on Ultrathin Fibronectin Fibres","volume":"42","author":"Ahmed","year":"1999","journal-title":"Cell Motil. Cytoskeleton"},{"key":"2026090211384276300_cit42","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1163\/156856207781494412","article-title":"Biomimetic Materials Replicating\nSchwann Cell Topography Enhance Neuronal Adhesion and Neurite Alignment in vitro","volume":"18","author":"Bruder","year":"2007","journal-title":"J. Biomater. Sci., Polym.\nEd."},{"key":"2026090211384276300_cit43","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.biomaterials.2007.10.025","article-title":"The Effect of the Alignment of Electrospun Fibrous\nScaffolds on Schwann Cell Maturation","volume":"29","author":"Chew","year":"2008","journal-title":"Biomaterials"},{"key":"2026090211384276300_cit44","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1089\/107632703322066606","article-title":"Tissue\u2013Engineered\nScaffolds are Effective Alternatives to Autografts for Bridging Peripheral\nNerve Gaps","volume":"9","author":"Yu","year":"2003","journal-title":"Tissue Eng."},{"key":"2026090211384276300_cit45","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-bioeng-070909-105351","article-title":"Topography,\nCell Response, and Nerve Regeneration","volume":"12","author":"Hoffman-Kim","year":"2010","journal-title":"Annu.\nRev. Biomed. Eng."}],"container-title":["ACS Applied\nMaterials &amp; Interfaces"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/am5018557","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/6\/12\/9472\/7746471\/am5018557.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/6\/12\/9472\/7746471\/am5018557.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:38:52Z","timestamp":1788363532000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aamick\/article\/6\/12\/9472\/763630\/Nerve-Guidance-Conduits-Based-on-Double-Layered"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,7]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,5,7]]},"published-print":{"date-parts":[[2014,6,25]]}},"URL":"https:\/\/doi.org\/10.1021\/am5018557","relation":{},"ISSN":["1944-8244","1944-8252"],"issn-type":[{"value":"1944-8244","type":"print"},{"value":"1944-8252","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,7]]}}}