title: Peripheral nerve morphogenesis induced by scaffold micropatterning.
abstract: Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous micro-structure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold's micro-structure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration.
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cerri
authors.affiliation: Department of Innovation Engineering, University of Lecce, Via per Monteroni, 73100 Lecce, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Salvatore
authors.affiliation: Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Robinson Way CB2 0PY, UK.
authors.forename: Danish
authors.initials: D
authors.lastname: Memon
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Filippo Martinelli
authors.initials: FM
authors.lastname: Boneschi
authors.affiliation: Department of Innovation Engineering, University of Lecce, Via per Monteroni, 73100 Lecce, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Madaghiele
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Del Carro
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Trimarco
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Ignazio D
authors.initials: ID
authors.lastname: Lopez
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Robinson Way CB2 0PY, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pluchino
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.affiliation: Department of Innovation Engineering, University of Lecce, Via per Monteroni, 73100 Lecce, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sannino
authors.affiliation: Division of Neuroscience and INSPE, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D057005:Bioengineering / Q000379:methods*; D005260:Female; D009416:Nerve Regeneration / Q000502:physiology*; D017933:Peripheral Nervous System / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials
keywords: Biomaterials; Medical device; Nerve regeneration; Peripheral nervous system