title: Engineering alginate for intervertebral disc repair.
abstract: Alginate is frequently studied as a scaffold for intervertebral disc (IVD) repair, since it closely mimics mechanical and cell-adhesive properties of the nucleus pulposus (NP) of the IVD. The aim of this study was to assess the relation between alginate concentration and scaffold stiffness and find preparation conditions where the viscoelastic behaviour mimics that of the NP. In addition, we measured the effect of variations in scaffold stiffness on the expression of extracellular matrix molecules specific to the NP (proteoglycans and collagen) by native NP cells. We prepared sample discs of different concentrations of alginate (1%-6%) by two different methods, diffusion and in situ gelation. The stiffness increased with increasing alginate concentration, while the loss tangent (dissipative behaviour) remained constant. The diffusion samples were ten-fold stiffer than samples prepared by in situ gelation. Sample discs prepared from 2% alginate by diffusion closely matched the stiffness and loss tangent of the NP. The stiffness of all samples declined upon prolonged incubation in medium, especially for samples prepared by diffusion. The biosynthetic phenotype of native cells isolated from NPs was preserved in alginate matrices up to 4 weeks of culturing. Gene expression levels of extracellular matrix components were insensitive to alginate concentration and corresponding matrix stiffness, likely due to the poor adhesiveness of the cells to alginate. In conclusion, alginate can mimic the viscoelastic properties of the NP and preserve the biosynthetic phenotype of NP cells but certain limitations like long-term stability still have to be addressed.
authors.affiliation: Department of Orthopaedic Surgery, VU University Medical Center, Amsterdam, The Netherlands. jl.bron@vumc.nl
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Bron
authors.forename: Lucienne A
authors.initials: LA
authors.lastname: Vonk
authors.forename: Theodoor H
authors.initials: TH
authors.lastname: Smit
authors.forename: Gijsje H
authors.initials: GH
authors.lastname: Koenderink
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005782:Gels; D005786:Gene Expression Regulation / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006041:Goats; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology* / Q000502:physiology; D055595:Mechanical Phenomena; D012212:Rheology; D012995:Solubility; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000464:Alginates; D005782:Gels; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002118:Calcium