Lower crosslinking density enhances functional nucleus pulposus-like matrix elaboration by human mesenchymal stem cells in carboxymethylcellulose hydrogels
Huizi A. Lin
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorMichelle S. Gupta
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorDevika M. Varma
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorM. Lane Gilchrist
Department of Chemical Engineering, The City College of New York, New York City, New York
Search for more papers by this authorCorresponding Author
Steven B. Nicoll
Department of Biomedical Engineering, The City College of New York, New York, New York
Correspondence to: S. B. Nicoll; e-mail: [email protected]Search for more papers by this authorHuizi A. Lin
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorMichelle S. Gupta
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorDevika M. Varma
Department of Biomedical Engineering, The City College of New York, New York, New York
Search for more papers by this authorM. Lane Gilchrist
Department of Chemical Engineering, The City College of New York, New York City, New York
Search for more papers by this authorCorresponding Author
Steven B. Nicoll
Department of Biomedical Engineering, The City College of New York, New York, New York
Correspondence to: S. B. Nicoll; e-mail: [email protected]Search for more papers by this authorThe II-II6B3 and X-AC9 monoclonal antibodies developed by T.F. Linsenmayer and 5C6 monoclonal antibody developed by E. Engvall were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA.
Disclosures: The authors have nothing to disclose.
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. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 165–177, 2016.
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