title: Biomimetic fibrin-hyaluronan hydrogels for nucleus pulposus regeneration.
abstract: OBJECTIVE
  To develop a biomimetic polymeric injectable hydrogel that can support nucleus pulposus (NP) regeneration.
  
  
  METHODS
  Natural polymer-based hydrogels were synthesized using fibrinogen (FBG) and hyaluronic acid (HA), conjugated by a novel two-step procedure. Bovine NP cells were cultured in FBG-HA conjugate-based 3D beads in vitro and in a nucleotomized organ culture model.
  
  
  RESULTS
  FBG-HA conjugate-based hydrogels prepared with 235 KDa HA at a FBG/HA w/w ratio of 17:1 showed superior gel stability and mechanical properties and markedly increased glycosaminoglycan synthesis compared with a FBG/HA mixture-based hydrogels or fibrin gels. Gene-expression levels of NP markers were maintained in vitro. In organ culture, NP cells seeded in FBG-HA conjugate-based hydrogels showed better integration with native NP tissue compared with fibrin gels. Moreover, FBG-HA conjugate-based hydrogels restored compressive stiffness and disc height after nucleotomy under dynamic load.
  
  
  CONCLUSIONS
  Specific FBG-HA conjugate-based hydrogels may be suitable as injectable materials for minimally invasive, biological NP regeneration.
authors.affiliation: AO Research Institute Davos, Davos, Switzerland.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Keren Mevorat
authors.initials: KM
authors.lastname: Kaplan
authors.forename: Abraham
authors.initials: A
authors.lastname: Wertzel
authors.forename: Marianna
authors.initials: M
authors.lastname: Peroglio
authors.forename: Boaz
authors.initials: B
authors.lastname: Amit
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.forename: Avner
authors.initials: A
authors.lastname: Yayon
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D040761:Biomimetic Materials / Q000737:chemistry / Q000627:therapeutic use*; D002417:Cattle; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D005337:Fibrin / Q000737:chemistry; D020869:Gene Expression Profiling; D006652:Histological Techniques; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels / Q000627:therapeutic use*; D007403:Intervertebral Disc / Q000502:physiology*; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D012038:Regeneration / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D020100:Hydrogels; D005337:Fibrin; D006820:Hyaluronic Acid
keywords: fibrinogen–hyaluronan conjugate; hydrogel; intervertebral disc; nucleus pulposus; regeneration