title: A combined biomaterial and cellular approach for annulus fibrosus rupture repair.
abstract: Recurrent intervertebral disc (IVD) herniation and degenerative disc disease have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy. An annulus fibrosus (AF) closure device that provides immediate closure of the AF rupture, restores disc height, reduces further disc degeneration and enhances self-repair capacities is an unmet clinical need. In this study, a poly(trimethylene carbonate) (PTMC) scaffold seeded with human bone marrow derived mesenchymal stromal cells (MSCs) and covered with a poly(ester-urethane) (PU) membrane was assessed for AF rupture repair in a bovine organ culture annulotomy model under dynamic load for 14 days. PTMC scaffolds combined with the sutured PU membrane restored disc height of annulotomized discs and prevented herniation of nucleus pulposus (NP) tissue. Implanted MSCs showed an up-regulated gene expression of type V collagen, a potential AF marker, indicating in situ differentiation capability. Furthermore, MSCs delivered within PTMC scaffolds induced an up-regulation of anabolic gene expression and down-regulation of catabolic gene expression in adjacent native disc tissue. In conclusion, the combined biomaterial and cellular approach has the potential to hinder herniation of NP tissue, stabilize disc height, and positively modulate cell phenotype of native disc tissue.
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pirvu
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, AE Enschede 7500, The Netherlands; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Sebastien B G
authors.initials: SB
authors.lastname: Blanquer
authors.affiliation: Department of Orthopaedic Surgery, University of Bern, Bern 3010, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Lorin M
authors.initials: LM
authors.lastname: Benneker
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, AE Enschede 7500, The Netherlands; University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Department of Biomedical Engineering, AD Groningen 9700, The Netherlands; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Grijpma
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Richards
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.affiliation: AO Research Institute Davos, Davos 7270, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Programme, AO Foundation, Davos 7270, Switzerland. Electronic address: zhen.li@aofoundation.org.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008567:Membranes, Artificial; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008855:Microscopy, Electron, Scanning; D011140:Polyurethanes / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012421:Rupture; D013194:Staining and Labeling; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D004146:Dioxanes; D006025:Glycosaminoglycans; D008567:Membranes, Artificial; D011140:Polyurethanes; D012333:RNA, Messenger; C443643:trimethylene carbonate; D004247:DNA
keywords: Annulus fibrosus rupture repair; Implantation; Mesenchymal stromal cells; Poly(esterurethane) membrane; Poly(trimethylene carbonate) scaffold