title: Hierarchically Ordered Porous and High-Volume Polycaprolactone Microchannel Scaffolds Enhanced Axon Growth in Transected Spinal Cords.
abstract: The goal of this work was to design nerve guidance scaffolds with a unique architecture to maximize the open volume available for nerve growth. Polycaprolactone (PCL) was selected as the scaffold material based on its biocompatibility and month-long degradation. Yet, dense PCL does not exhibit suitable properties such as porosity, stiffness, strength, and cell adhesion to function as an effective nerve guidance scaffold. To address these shortcomings, PCL was processed using a modified salt-leaching technique to create uniquely controlled interconnected porosity. By controlling porosity, we demonstrated that the elastic modulus could be controlled between 2.09 and 182.1 MPa. In addition, introducing porosity and/or coating with fibronectin enhanced the PCL cell attachment properties. To produce PCL scaffolds with maximized open volume, porous PCL microtubes were fabricated and translated into scaffolds with 60 volume percent open volume. The scaffolds were tested in transected rat spinal cords. Linear axon growth within both the microtubes as well as the interstitial space between the tubes was observed, demonstrating that the entire open volume of the scaffold was available for nerve growth. Overall, a novel scaffold architecture and fabrication technique are presented. The scaffolds exhibit significantly higher volume than state-of-the-art scaffolds for promising spinal cord nerve repair.
authors.affiliation: 1 Department of Macromolecular Science and Engineering, University of Michigan , Ann Arbor, Michigan.
authors.forename: Dena
authors.initials: D
authors.lastname: Shahriari
authors.affiliation: 2 Department of Neuroscience, University of California San Diego , La Jolla, California.
authors.forename: Jacob Y
authors.initials: JY
authors.lastname: Koffler
authors.affiliation: 2 Department of Neuroscience, University of California San Diego , La Jolla, California.|3 Veterans Administration Medical Center , La Jolla, California.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
authors.affiliation: 4 Department of Anesthesiology, University of California San Diego , La Jolla, California.|5 Program in Neuroscience, University of California San Diego , La Jolla, California.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Campana
authors.affiliation: 1 Department of Macromolecular Science and Engineering, University of Michigan , Ann Arbor, Michigan.|6 Department of Mechanical Engineering, University of Michigan , Ann Arbor, Michigan.
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051379:Mice; D041681:NIH 3T3 Cells; D011091:Polyesters / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D011091:Polyesters; C016240:polycaprolactone
keywords: controlled porosity; mechanical properties; nerve guidance scaffolds; nerve regeneration; polycaprolactone