title: In vivo biofunctional evaluation of hydrogels for disc regeneration.
abstract: OBJECTIVE
  Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model.
  
  
  METHODS
  In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted.
  
  
  RESULTS
  Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration.
  
  
  CONCLUSIONS
  None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reitmaier
authors.forename: Ludwika
authors.initials: L
authors.lastname: Kreja
authors.forename: Katharina
authors.initials: K
authors.lastname: Gruchenberg
authors.forename: Britta
authors.initials: B
authors.lastname: Kanter
authors.forename: Joana
authors.initials: J
authors.lastname: Silva-Correia
authors.forename: Joaquim Miguel
authors.initials: JM
authors.lastname: Oliveira
authors.forename: Rui Luís
authors.initials: RL
authors.lastname: Reis
authors.forename: Valeria
authors.initials: V
authors.lastname: Perugini
authors.forename: Matteo
authors.initials: M
authors.lastname: Santin
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wilke
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D016026:Bone Marrow Transplantation; D017587:Diskectomy, Percutaneous; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D020100:Hydrogels / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007403:Intervertebral Disc / Q000502:physiology*; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D012038:Regeneration / Q000502:physiology*; D012756:Sheep
chemical_list: D020533:Angiogenesis Inhibitors; D001672:Biocompatible Materials; D020100:Hydrogels; D006820:Hyaluronic Acid