{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:18:31Z","timestamp":1792675111422,"version":"4.5.0"},"reference-count":41,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01EB014986-01"],"award-info":[{"award-number":["R01EB014986-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Mater."],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In a previous study, we demonstrated a novel manufacturing approach to fabricate multi-channel scaffolds (MCS) for use in spinal cord injuries (SCI). In the present study, we extended similar materials processing technology to fabricate significantly longer (5X) porous poly caprolactone (PCL) MCS and evaluated their efficacy in 1 cm sciatic peripheral nerve injury (PNI) model. Due to the increase in MCS dimensions and the challenges that may arise in a longer nerve gap model, microstructural characterization involved MCS wall permeability to assess nutrient flow, topography, and microstructural uniformity to evaluate the potential for homogeneous linear axon guidance. It was determined that the wall permeability dramatically varied from 0.02\u00a0\u00b1\u00a00.01\u00a0\u00d7\u00a010\n                    <jats:sup>\u221213<\/jats:sup>\n                    to 21.7\u00a0\u00b1\u00a011.4\u00a0\u00d7\u00a010\n                    <jats:sup>\u221213<\/jats:sup>\n                    m\n                    <jats:sup>2<\/jats:sup>\n                    for 50% and 70% porous PCL, respectively. Using interferometry, the porous PCL surface roughness was determined to be 10.7\u00a0\u00b1\u00a01.2\n                    <jats:italic>\u03bc<\/jats:italic>\n                    m, which is believed to be sufficient to promote cell integration. Using micro computed tomography, the 3D MCS microstructure was determined to be uniform over 1 cm with an open lumen volume of 44.6%\u00a0\u00b1\u00a03.6%.\n                    <jats:italic>In vivo<\/jats:italic>\n                    implantation, in the rat sciatic nerve model, over 4 weeks, demonstrated that MCS scaffolds maintained structural integrity, were biocompatible, and supported linear axon guidance and distal end egress over 1 cm. Taken together, this study demonstrated that MCS technology previously developed for the SCI is also relevant to longer nerve gap PNI.\n                  <\/jats:p>","DOI":"10.1088\/1748-605x\/aaad85","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T07:45:14Z","timestamp":1517989514000},"page":"044104","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Microstructure and\n                    <i>in vivo<\/i>\n                    characterization of multi-channel nerve guidance scaffolds"],"prefix":"10.1088","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-4136","authenticated-orcid":false,"given":"K M","family":"Pawelec","sequence":"first","affiliation":[{"name":"University of Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Koffler","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Shahriari","sequence":"additional","affiliation":[{"name":"University of Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Galvan","sequence":"additional","affiliation":[{"name":"University of Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M H","family":"Tuszynski","sequence":"additional","affiliation":[{"name":"University of California"},{"name":"Veterans Administration Medical Center, La Jolla, CA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"University of Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"bmmaaad85bib1","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1097\/BOT.0b013e31823f000e","type":"journal-article","article-title":"Fate of combat nerve injury","volume":"26","author":"Beltran","year":"2012","journal-title":"J. Orthopaedic Trauma"},{"key":"bmmaaad85bib2","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1098\/rsif.2011.0438","type":"journal-article","article-title":"A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery","volume":"9","author":"Daly","year":"2012","journal-title":"J. R. Soc. Interface"},{"key":"bmmaaad85bib3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1615\/CritRevBiomedEng.v39.i2.20","type":"journal-article","article-title":"Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges","volume":"39","author":"Pfister","year":"2011","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"bmmaaad85bib4","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.expneurol.2004.09.018","type":"journal-article","article-title":"BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury","volume":"191","author":"Lu","year":"2005","journal-title":"Exp. Neurol."},{"key":"bmmaaad85bib5","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.ejpb.2008.01.014","type":"journal-article","article-title":"Controlled nerve growth factor release from multi-ply alginate\/chitosan-based nerve conduits","volume":"69","author":"Pfister","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"bmmaaad85bib6","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1002\/bit.22766","type":"journal-article","article-title":"Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration","volume":"106","author":"Wood","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"bmmaaad85bib7","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/j.jhsa.2008.05.034","type":"journal-article","article-title":"Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model","volume":"33A","author":"Apel","year":"2008","journal-title":"J. Hand Surg."},{"key":"bmmaaad85bib8","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.expneurol.2009.09.009","type":"journal-article","article-title":"Current applications and future perspectives of artificial nerve conduits","volume":"223","author":"Jiang","year":"2010","journal-title":"Exp. Neurol."},{"key":"bmmaaad85bib9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1179\/016164104225013798","type":"journal-article","article-title":"Peripheral nerve regeneration through guidance tubes","volume":"26","author":"Belkas","year":"2004","journal-title":"Neurol. Res."},{"key":"bmmaaad85bib10","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1016\/j.biomaterials.2006.02.030","type":"journal-article","article-title":"Peripheral nerve regeneration: an opinion on channels, scaffolds and anisotropy","volume":"27","author":"Bellamkonda","year":"2006","journal-title":"Biomaterials"},{"key":"bmmaaad85bib11","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1089\/ten.2006.12.2777","type":"journal-article","article-title":"Templated agarose scaffolds support linear axonal regeneration","volume":"12","author":"Stokols","year":"2006","journal-title":"Tissue Eng."},{"key":"bmmaaad85bib12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/micr.20975","type":"journal-article","article-title":"Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions","volume":"32","author":"Brooks","year":"2012","journal-title":"Microsurgery"},{"key":"bmmaaad85bib13","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1089\/107632703322066606","type":"journal-article","article-title":"Tissue-engineered scaffolds are effective alternatives to autografts for bridging peripheral nerve gaps","volume":"9","author":"Yu","journal-title":"Tissue Eng."},{"key":"bmmaaad85bib14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.biomaterials.2017.03.038","type":"journal-article","article-title":"Design and optimization of a biodegradable porous zein conduit using microtubes as a guide for rat sciatic nerve defect repair","volume":"131","author":"Wang","year":"2017","journal-title":"Biomaterials"},{"key":"bmmaaad85bib15","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1016\/j.actbio.2009.03.021","type":"journal-article","article-title":"Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord","volume":"5","author":"Krych","year":"2009","journal-title":"Acta Biomater."},{"key":"bmmaaad85bib16","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1089\/ten.tec.2010.0152","type":"journal-article","article-title":"Multi-channeled collagen conduits for peripheral nerve regeneration: design, fabrication, and characterization","volume":"16","author":"Yao","year":"2010","journal-title":"Tissue Eng. C"},{"key":"bmmaaad85bib17","doi-asserted-by":"publisher","first-page":"6719","DOI":"10.1016\/j.biomaterials.2010.04.035","type":"journal-article","article-title":"Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds","volume":"31","author":"Gros","year":"2010","journal-title":"Biomaterials"},{"key":"bmmaaad85bib18","doi-asserted-by":"publisher","first-page":"3392","DOI":"10.1002\/jbm.a.36186","type":"journal-article","article-title":"Peripheral nerve growth within a hydrogel microchannel scaffold supported by a kink-resistant conduit","volume":"105A","author":"Shahriari","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"bmmaaad85bib19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1089\/ten.tea.2016.0378","type":"journal-article","article-title":"Hierarchically ordered porous and high volume polycaprolactone microchannel scaffolds enhanced axon growth in transected spinal cords","volume":"23","author":"Shahriari","year":"2017","journal-title":"Tissue Eng. A"},{"key":"bmmaaad85bib20","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.msec.2017.03.142","type":"journal-article","article-title":"Ice-templating of anisotropic structures with high permeability","volume":"76","author":"Pawelec","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"bmmaaad85bib21","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1007\/s10439-013-0815-5","type":"journal-article","article-title":"A survey of methods for the evaluation of tissue engineering scaffold permeability","volume":"41","author":"Pennella","year":"2013","journal-title":"Ann. Biomed. Eng."},{"key":"bmmaaad85bib22","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1016\/j.biomaterials.2012.10.070","type":"journal-article","article-title":"Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection","volume":"34","author":"Gao","year":"2013","journal-title":"Biomaterials"},{"key":"bmmaaad85bib23","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1021\/bp020280h","type":"journal-article","article-title":"Development of a bioartificial nerve graft: II. Nerve regeneration in vitro","volume":"18","author":"Rutkowski","year":"2002","journal-title":"Biotechnol. Prog."},{"key":"bmmaaad85bib24","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.1016\/j.actbio.2009.03.009","type":"journal-article","article-title":"Diffusion of soluble factors through degradable polymer nerve guides: controlling manufacturing parameters","volume":"5","author":"Kokai","year":"2009","journal-title":"Acta Biomater."},{"key":"bmmaaad85bib25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/2041731416629471","type":"journal-article","article-title":"Design of barrier coating on kink-resistant peripheral nerve conduits","volume":"7","author":"Clements","year":"2016","journal-title":"J. Tissue Eng."},{"key":"bmmaaad85bib26","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1016\/j.biomaterials.2008.10.056","type":"journal-article","article-title":"The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth","volume":"30","author":"Jones","year":"2009","journal-title":"Biomaterials"},{"key":"bmmaaad85bib27","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700954","type":"journal-article","article-title":"A physicochemically optimized and neuroconductive biphasic nerve guidance conduit for peripheral nerve repair","volume":"6","author":"Ryan","year":"2017","journal-title":"Adv. Healthcare Mater."},{"key":"bmmaaad85bib28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3233\/THC-2007-15102","type":"journal-article","article-title":"The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering","volume":"15","author":"O\u2019Brien","year":"2007","journal-title":"Technol. Health Care"},{"key":"bmmaaad85bib29","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.biomaterials.2009.09.063","type":"journal-article","article-title":"The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering","volume":"31","author":"Murphy","year":"2010","journal-title":"Biomaterials"},{"key":"bmmaaad85bib30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s11671-015-0972-6","type":"journal-article","article-title":"A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells","volume":"10","author":"Jenkins","year":"2015","journal-title":"Nanoscale Res. Lett."},{"key":"bmmaaad85bib31","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1021\/acsbiomaterials.6b00344","type":"journal-article","article-title":"Biomimetic nerve guidance conduit containing intraluminal microchannel with aligned nanofibers markedly facilitates in nerve regeneration","volume":"2","author":"Lee","year":"2016","journal-title":"ACS Biomater. Sci. Eng."},{"key":"bmmaaad85bib32","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/13\/6\/066011","type":"journal-article","article-title":"BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration","volume":"13","author":"Gao","year":"2016","journal-title":"J. Neural Eng."},{"key":"bmmaaad85bib33","doi-asserted-by":"publisher","first-page":"5789","DOI":"10.1016\/j.biomaterials.2010.03.081","type":"journal-article","article-title":"Controlling dispersion of axonal regeneration using a multichannel collagen nerve conduit","volume":"31","author":"Yao","year":"2010","journal-title":"Biomaterials"},{"key":"bmmaaad85bib34","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.pneurobio.2015.06.001","type":"journal-article","article-title":"Trends in the design of nerve guidance channels in peripheral nerve tissue engineering","volume":"131","author":"Chiono","year":"2015","journal-title":"Prog. Neurobiol."},{"key":"bmmaaad85bib35","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1089\/ten.tea.2012.0124","type":"journal-article","article-title":"Extracellular matrix molecules enhance the neurotrophic effect of schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions","volume":"19","author":"di Summa","year":"2013","journal-title":"Tissue Eng. A"},{"key":"bmmaaad85bib36","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1227\/01.NEU.0000335081.47352.78","type":"journal-article","article-title":"Accuracy of motor axon regeneration across autograft, single-lumen, and multichannel poly(lactic-co-glycolic acid) nerve tubes","volume":"63","author":"de Ruiter","year":"2008","journal-title":"Neurosurgery"},{"key":"bmmaaad85bib37","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.biomaterials.2011.10.069","type":"journal-article","article-title":"The role of micro-structured and interconnected pore channels in a collagen-based nerve guide on axonal regeneration in peripheral nerves","volume":"33","author":"Bozkurt","year":"2012","journal-title":"Biomaterials"},{"key":"bmmaaad85bib38","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1002\/sctm.16-0420","type":"journal-article","article-title":"Olfactory derived stem cells delivered in a biphasic conduit promote peripheral nerve repair in vivo","volume":"6","author":"Roche","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"bmmaaad85bib39","doi-asserted-by":"publisher","first-page":"3117","DOI":"10.1016\/j.biomaterials.2008.03.042","type":"journal-article","article-title":"The role of aligned polymer fiber-based constructs in the bridging of long peripheral nerve gaps","volume":"29","author":"Kim","year":"2008","journal-title":"Biomaterials"},{"key":"bmmaaad85bib40","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.progpolymsci.2010.04.002","type":"journal-article","article-title":"The return of a forgotten polymer\u2014polycaprolactone in the 21st century","volume":"35","author":"Woodruff","year":"2010","journal-title":"Prog. Polym. Sci."},{"key":"bmmaaad85bib41","doi-asserted-by":"publisher","first-page":"4573","DOI":"10.1016\/j.biomaterials.2009.05.011","type":"journal-article","article-title":"Neurite infiltration and cell-cell response to electrospun polycaprolactone scaffolds implanted into the brain","volume":"30","author":"Nisbet","year":"2009","journal-title":"Biomaterials"}],"container-title":["Biomedical Materials"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85","content-type":"text\/html","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T13:51:59Z","timestamp":1779544319000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/aaad85"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,25]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,25]]},"published-print":{"date-parts":[[2018,7,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1748-605x\/aaad85","relation":{},"ISSN":["1748-6041","1748-605X"],"issn-type":[{"value":"1748-6041","type":"print"},{"value":"1748-605X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,25]]},"assertion":[{"value":"Microstructure and\n                      in vivo\n                      characterization of multi-channel nerve guidance scaffolds","name":"article_title","label":"Article Title"},{"value":"Biomedical Materials","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2018 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2017-08-10","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2018-02-07","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2018-04-25","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}