title: Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement.
abstract: Nucleus pulposus (NP) replacement offers a minimally invasive alternative to spinal fusion or total disc replacement for the treatment of intervertebral disc (IVD) degeneration. This study aimed to develop a cytocompatible NP replacement material, which is feasible for non-invasive delivery and tunable design, and allows immediate mechanical restoration of the IVD. A bi-phasic polyurethane scaffold was fabricated consisting of a core material with rapid swelling property and a flexible electrospun envelope. The scaffold was assessed in a bovine whole IVD organ culture model under dynamic load for 14 days. Nucleotomy was achieved by incision through the endplate without damaging the annulus fibrosus. After implantation of the scaffold and in situ swelling, the dynamic compressive stiffness and disc height were restored immediately. The scaffold also showed favorable cytocompatibility for native disc cells. Implantation of the scaffold in a partially nucleotomized IVD down-regulated catabolic gene expression, increased proteoglycan and type II collagen intensity and decreased type I collagen intensity in remaining NP tissue, indicating potential to retard degeneration and preserve the IVD cell phenotype. The scaffold can be delivered in a minimally invasive manner, and the geometry of the scaffold post-hydration is tunable by adjusting the core material, which allows individualized design.
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: AO Research Institute Davos, Davos, Switzerland; Department of Orthopedic and Trauma Surgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Lang
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Nicast Ltd., Lod, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Sacks
authors.affiliation: Nicast Ltd., Lod, Israel.
authors.forename: Carmit
authors.initials: C
authors.lastname: Mantzur
authors.affiliation: Nicast Ltd., Lod, Israel.
authors.forename: Udi
authors.initials: U
authors.lastname: Tropp
authors.affiliation: Sheffield Hallam University, Sheffield, United Kingdom.
authors.forename: Kerstin T
authors.initials: KT
authors.lastname: Mader
authors.affiliation: Sheffield Hallam University, Sheffield, United Kingdom.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smallwood
authors.affiliation: Sheffield Hallam University, Sheffield, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Sammon
authors.affiliation: AO Research Institute Davos, Davos, Switzerland; Department of Orthopedic and Trauma Surgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: R Geoff
authors.initials: RG
authors.lastname: Richards
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Davos, Switzerland. Electronic address: sibylle.grad@aofoundation.org.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
mesh_terms: D000818:Animals; D002417:Cattle; D002452:Cell Count; D002478:Cells, Cultured; D017587:Diskectomy, Percutaneous; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000601:surgery; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011140:Polyurethanes / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D016474:Weight-Bearing
chemical_list: D011140:Polyurethanes
keywords: Biphasic polyurethane scaffold; In situ swelling; Intervertebral disc degeneration; Nucleotomy; Nucleus pulposus replacement; Organ culture