title: A comparison of the performance of mono- and bi-component electrospun conduits in a rat sciatic model.
abstract: Synthetic nerve conduits represent a promising strategy to enhance functional recovery in peripheral nerve injury repair. However, the efficiency of synthetic nerve conduits is often compromised by the lack of molecular factors to create an enriched microenvironment for nerve regeneration. Here, we investigate the in vivo response of mono (MC) and bi-component (BC) fibrous conduits obtained by processing via electrospinning poly(ε-caprolactone) (PCL) and gelatin solutions. In vitro studies demonstrate that the inclusion of gelatin leads to uniform electrospun fiber size and positively influences the response of Dorsal Root Ganglia (DRGs) neurons as confirmed by the preferential extensions of neurites from DRG bodies. This behavior can be attributed to gelatin as a bioactive cue for the cultured DRG and to the reduced fibers size. However, in vivo studies in rat sciatic nerve defect model show an opposite response: MC conduits stimulate superior nerve regeneration than gelatin containing PCL conduits as confirmed by electrophysiology, muscle weight and histology. The G-ratio, 0.71 ± 0.07 for MC and 0.66 ± 0.05 for autograft, is close to 0.6, the value measured in healthy nerves. In contrast, BC implants elicited a strong host response and infiltrating tissue occluded the conduits preventing the formation of myelinated axons. Therefore, although gelatin promotes in vitro nerve regeneration, we conclude that bi-component electrospun conduits are not satisfactory in vivo due to intrinsic limits to their mechanical performance and degradation kinetics, which are essential to peripheral nerve regeneration in vivo.
authors.affiliation: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Naples Federico II, P.leTecchio 80, Naples 80125, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirillo
authors.affiliation: New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA.
authors.forename: Basak A
authors.initials: BA
authors.lastname: Clements
authors.affiliation: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy. Electronic address: vguarino@unina.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Guarino
authors.affiliation: New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Bushman
authors.affiliation: New Jersey Center for Biomaterials, Rutgers - The State University of NJ, 145 Bevier Road, Piscataway, NJ 08854, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kohn
authors.affiliation: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale Kennedy 54, Naples 80125, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ambrosio
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D005780:Gelatin / Q000737:chemistry; D018482:Muscle, Skeletal / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000628:therapy; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology / Q000473:pathology; D020426:Sciatic Neuropathy / Q000628:therapy*
chemical_list: D011091:Polyesters; C016240:polycaprolactone; D005780:Gelatin
keywords: Electrospinning; In vivo model; Sciatic nerve regeneration; Tubular conduit
references.citation: Adv Drug Deliv Rev. 2009 Oct 5;61(12):1055-64
references.pmid: 19643156
references.citation: Prog Neurobiol. 2011 Feb;93(2):204-30
references.pmid: 21130136
references.citation: Biomaterials. 2006 Jan;27(3):497-504
references.pmid: 16099038
references.citation: Exp Neurol. 2010 May;223(1):86-101
references.pmid: 19769967
references.citation: J Reconstr Microsurg. 2012 Nov;28(9):581-7
references.pmid: 22711205
references.citation: Nanomedicine (Lond). 2009 Jan;4(1):11-30
references.pmid: 19093893
references.citation: J Neurosurg. 2003 Sep;99(3):555-65
references.pmid: 12959445
references.citation: Acta Biomater. 2009 Sep;5(7):2540-50
references.pmid: 19369123
references.citation: Biomaterials. 2014 Apr;35(13):4035-4045
references.pmid: 24559639
references.citation: Biomaterials. 2007 Dec;28(36):5526-35
references.pmid: 17884161
references.citation: Biomaterials. 1999 Mar;20(6):573-88
references.pmid: 10213360
references.citation: BMC Neurosci. 2011 Jul 15;12:68
references.pmid: 21756368
references.citation: J Mater Sci Mater Med. 2008 Mar;19(3):1127-32
references.pmid: 17701295
references.citation: J Biomater Sci Polym Ed. 2007;18(7):843-63
references.pmid: 17688744
references.citation: Neurosci Lett. 2013 Jun 7;544:125-30
references.pmid: 23583695
references.citation: Biotechnol Bioeng. 2011 Aug;108(8):1965-76
references.pmid: 21351071
references.citation: Biomaterials. 2007 Oct;28(30):4449-60
references.pmid: 17643485
references.citation: Artif Organs. 2007 Jul;31(7):500-8
references.pmid: 17584474
references.citation: Biomaterials. 2008 Dec;29(34):4532-9
references.pmid: 18757094
references.citation: Brain Res. 2005 Jun 7;1046(1-2):55-67
references.pmid: 15927550
references.citation: Biotechnol Lett. 2007 Nov;29(11):1697-702
references.pmid: 17628751
references.citation: Adv Drug Deliv Rev. 2007 Dec 10;59(14):1392-412
references.pmid: 17884240
references.citation: J Long Term Eff Med Implants. 2011;21(2):93-122
references.pmid: 22043969
references.citation: J Biomed Mater Res A. 2012 Nov;100(11):3008-19
references.pmid: 22700476
references.citation: J Tissue Eng Regen Med. 2014 Feb;8(2):153-63
references.pmid: 22508573
references.citation: Biomaterials. 2005 Jun;26(16):3083-91
references.pmid: 15603803
references.citation: Biomacromolecules. 2010 Sep 13;11(9):2238-46
references.pmid: 20690634
references.citation: J Hand Surg Br. 1994 Jun;19(3):273-6
references.pmid: 8077807
references.citation: J Am Acad Orthop Surg. 2012 Feb;20(2):63-8
references.pmid: 22302443
references.citation: J Biomed Mater Res A. 2006 Oct;79(1):36-46
references.pmid: 16758450
references.citation: Biomacromolecules. 2004 Mar-Apr;5(2):463-73
references.pmid: 15003007
references.citation: Tissue Eng Part A. 2008 Nov;14(11):1787-97
references.pmid: 18657027
references.citation: Tissue Eng Part C Methods. 2011 Jul;17(7):705-15
references.pmid: 21501089
references.citation: J Biomed Mater Res A. 2003 Nov 1;67(2):531-7
references.pmid: 14566795
references.citation: Br J Plast Surg. 2002 Apr;55(3):235-40
references.pmid: 12041978
references.citation: Brain. 2005 Aug;128(Pt 8):1897-910
references.pmid: 15872018
references.citation: Tissue Eng Part A. 2014 Feb;20(3-4):518-28
references.pmid: 24011026
references.citation: Biomaterials. 2002 Jun;23(12):2607-14
references.pmid: 12033610
references.citation: Biomaterials. 2005 Jun;26(18):3911-8
references.pmid: 15626438
references.citation: Biomaterials. 2009 Jan;30(2):217-25
references.pmid: 18849069
references.citation: Biotechnol Prog. 2002 Mar-Apr;18(2):373-9
references.pmid: 11934309
references.citation: J Neurosci Res. 2003 Apr 15;72(2):227-38
references.pmid: 12671998
references.citation: Microsurgery. 2005;25(6):508-19
references.pmid: 16145683
references.citation: Biomaterials. 2008 May;29(15):2293-305
references.pmid: 18313748
references.citation: J Biomed Mater Res B Appl Biomater. 2006 Apr;77(1):89-97
references.pmid: 16211569
references.citation: Tissue Eng Part C Methods. 2009 Mar;15(1):11-21
references.pmid: 18844601
references.citation: J R Soc Interface. 2012 Feb 7;9(67):202-21
references.pmid: 22090283
references.citation: Adv Drug Deliv Rev. 2007 May 30;59(4-5):325-38
references.pmid: 17482308
references.citation: J Biomed Mater Res A. 2008 Feb;84(2):557-66
references.pmid: 17941013
references.citation: Tissue Eng Part C Methods. 2013 Mar;19(3):233-43
references.pmid: 22871377
references.citation: Biomaterials. 2008 Mar;29(8):955-62
references.pmid: 18082253
references.citation: Microsurgery. 2011 May;31(4):293-302
references.pmid: 21400584
references.citation: J Mater Sci Mater Med. 2008 Feb;19(2):847-54
references.pmid: 17665116
references.citation: Artif Cells Blood Substit Immobil Biotechnol. 2006;34(1):89-97
references.pmid: 16519406
references.citation: Biomaterials. 2008 Apr;29(11):1601-9
references.pmid: 18155135
references.citation: Curr Pharm Des. 2006;12(36):4751-70
references.pmid: 17168776
references.citation: Biomaterials. 2007 Jul;28(19):3012-25
references.pmid: 17408736
references.citation: Scand J Plast Reconstr Surg Hand Surg. 2005;39(3):129-37
references.pmid: 16019744
references.citation: J Hand Surg Am. 2007 Dec;32(10):1521-9
references.pmid: 18070638
references.citation: Macromol Biosci. 2011 Dec 8;11(12):1694-705
references.pmid: 22052674