title: Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment of the degenerating intervertebral disc.
abstract: OBJECTIVE
  The early stages of degenerative disc disease (DDD) primarily affect the disc nucleus pulposus (NP). Tissue-engineered strategies may enhance intervertebral disc (IVD) functionality. The aim of this study was to develop and evaluate a novel deacetylated poly-N-acetyl glucosamine (pGlcNAc) hydrogel characterizing its biochemical effect on human IVD cells as well as material biomechanical properties.
  
  
  METHODS
  A novel deacetylated derivative of a marine diatom-derived glycosaminoglycan was developed into a hydrogel formulation as a potential therapy to treat degenerating IVD NP. In vitro biochemical studies were conducted using primary human disc cell cultures to evaluate cell viability, metabolic activity, proteoglycan and extracellular matrix protein expression. The biomechanical hydration kinetics and viscoelastic behavior of the hydrogel were determined and compared with the behavior of human lumbar NP.
  
  
  RESULTS
  Disc cell viability, metabolic activity, and proteoglycan content of the treated cells were observed to be significantly greater in experimental samples when compared to untreated control groups. RT-PCR and immunohistochemical data corroborated the expression of characteristic NP disc markers, aggrecan and type II collagen in cultured cells. Rheological data demonstrated that the elastic component of the hydrogel dominated the viscous component over a frequency range of 0.1 to 15.85rad/s. Of several formulations evaluated, a sulphated, deactylated derivative of the nanofiber derived pGlcNAc hydrogel demonstrated the most robust biologic effects on cell viability, metabolic activity, and proteoglycan expression.
  
  
  CONCLUSIONS
  This in vitro study using human disc cells demonstrates that a sulphated deacetylated glycosaminoglycan derivative hydrogel possesses promising characteristics motivating further evaluation as a potential therapy for NP degeneration.
authors.affiliation: Division of Orthopaedic Surgery, University of Toronto, Canada.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Gorapalli
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
authors.forename: John
authors.initials: J
authors.lastname: Vournakis
authors.forename: Cari
authors.initials: C
authors.lastname: Whyne
authors.forename: Margarete
authors.initials: M
authors.lastname: Akens
authors.forename: Aiguo
authors.initials: A
authors.lastname: Zhang
authors.forename: Marina
authors.initials: M
authors.lastname: Demcheva
authors.forename: Erion
authors.initials: E
authors.lastname: Qamirani
authors.forename: Albert
authors.initials: A
authors.lastname: Yee
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology*; D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D024043:Collagen Type II / Q000378:metabolism; D017377:Diatoms / Q000378:metabolism; D004548:Elasticity; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D020100:Hydrogels; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods; D014783:Viscosity
chemical_list: D024043:Collagen Type II; D020100:Hydrogels; D011509:Proteoglycans; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine