title: Development of an ex vivo cavity model to study repair strategies in loaded intervertebral discs.
abstract: The aim of this study was to compare two approaches for the delivery of biomaterials to partially nucleotomised intervertebral discs in whole organ culture under loading. Such models can help to bridge the gap between in vitro and in vivo studies by assessing (1) suitability of biomaterial delivery and defect closure methods, (2) effect of mechanical loading and (3) tissue response.
  
  
  
  Mechanical performance of bovine discs filled with a hyaluronan-based thermoreversible hydrogel delivered through the annulus fibrosus (AF) or the bony endplate (EP) was evaluated under cyclic axial loading in a bioreactor. The loading protocol was optimised to achieve physiological disc height changes in nucleotomised discs. A loading regime of 0.06 ± 0.02 MPa, 0.1 Hz, 6 h daily was applied on the nucleotomised discs. Disc height and stiffness were tracked for 5 days, followed by histological analyses.
  
  
  
  Creation of a defect is less demanding for AF approach, while sealing is superior with the EP approach. Dynamic compressive stiffness is reduced following nucleotomy, with no significant difference between the two approaches. Disc height loss was higher, disc height recovery was lower and region around the defect with reduced cell viability was smaller for AF-approached than EP-approached discs.
  
  
  
  Two alternative methods for biomaterial testing in whole organ culture under loading were developed. Such models bring insights on the ability of the biomaterial to restore the mechanical behaviour of the discs. From a clinical perspective, the cavity models can simulate treatment of nucleotomy after disc herniation in young patients, whereby the remaining nucleus pulposus is still functional and therefore at high risk of re-herniation, though the defect may differ from the clinical situation.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lezuo
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland.
authors.forename: Girish
authors.initials: G
authors.lastname: Pattappa
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
authors.forename: Estelle
authors.initials: E
authors.lastname: Collin
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland. marianna.peroglio@aofoundation.org.
authors.forename: Marianna
authors.initials: M
authors.lastname: Peroglio
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D002417:Cattle; D002470:Cell Survival; D004195:Disease Models, Animal; D017586:Diskectomy / Q000379:methods; D006820:Hyaluronic Acid / Q000627:therapeutic use; D020100:Hydrogels / Q000627:therapeutic use; D007403:Intervertebral Disc / Q000473:pathology / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000628:therapy*; D007405:Intervertebral Disc Displacement / Q000473:pathology; D008422:Materials Testing / Q000379:methods; D008954:Models, Biological; D009924:Organ Culture Techniques / Q000379:methods; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: Bioreactor; Cyclic loading; Lactate dehydrogenase; Nucleotomy; Whole organ culture