title: Lower crosslinking density enhances functional nucleus pulposus-like matrix elaboration by human mesenchymal stem cells in carboxymethylcellulose hydrogels.
abstract: Engineered constructs represent a promising treatment for replacement of nucleus pulposus (NP) tissue. Recently, photocrosslinked hydrogels comprised of methacrylated carboxymethylcellulose (CMC) were shown to support chondrogenic differentiation of encapsulated human mesenchymal stem cells (hMSCs) and promote accumulation of NP-like extracellular matrix (ECM). The objective of this study was to investigate the influence of CMC crosslinking density, by varying macromer concentration and modification (i.e., methacrylation) percentage, on NP-like differentiation of encapsulated hMSCs. Constructs of lower macromer concentration (2%, w/v) exhibited significantly greater collagen II accumulation, more homogeneous distribution of ECM macromolecules, and a temporal increase in mechanical properties compared to hydrogels of higher macromer concentration (4%, w/v). Constructs of higher modification percentage (25%) gave rise to significantly elevated collagen II content and the formation of cell clusters within the matrix relative to samples of lower modification percentage (10% and 15%). These differences in functional ECM accumulation and distribution are likely attributed to the distinct crosslinked network structures of the various hydrogel formulations. Overall, CMC constructs of lower macromer concentration and modification percentage were most promising as scaffolds for NP tissue engineering based on functional ECM assembly. Optimization of such hydrogel fabrication parameters may lead to the development of clinically relevant tissue-engineered NP replacements.
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, New York.
authors.forename: Huizi A
authors.initials: HA
authors.lastname: Lin
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, New York.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Gupta
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, New York.
authors.forename: Devika M
authors.initials: DM
authors.lastname: Varma
authors.affiliation: Department of Chemical Engineering, The City College of New York, New York City, New York.
authors.forename: M Lane
authors.initials: ML
authors.lastname: Gilchrist
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, New York.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Nicoll
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D012996:Solutions; D014783:Viscosity
chemical_list: D003432:Cross-Linking Reagents; D020100:Hydrogels; D012996:Solutions; D002266:Carboxymethylcellulose Sodium
keywords: carboxymethylcellulose; hydrogel; mesenchymal stem cells; nucleus pulposus; tissue engineering