A Chitosan-Hyaluronan-Based Hydrogel-Hydrocolloid Supports In Vitro Culture and Differentiation of Human Mesenchymal Stem/Stromal Cells
Abstract
Three-dimensional (3D) cell culture platforms are increasingly utilized due to their ability to more closely mimic the in vivo microenvironment compared to traditional two-dimensional methods. Limitations of currently available 3D materials include lack of cell attachment, long polymerization times, and inclusion of undefined xenobiotics, and cytotoxic cross-linkers. Evaluated here is a unique hydrogel comprised of polyelectrolytic complex (PEC) fibers formed by hyaluronic acid and chitosan (CT). When hydrated with fetal bovine serum containing human mesenchymal stem/stromal cells (hMSCs), a hydrogel with an elastic modulus of 264±38 Pa formed in seconds with cells distributed throughout the matrix. Scanning electron microscopy showed a lattice-like meshwork of PEC fibers forming irregular compartments. hMSCs showed 48% viability during the first 24 h, with cell populations thereafter reaching a steady state for 14 days. hMSCs in the matrix were induced to differentiate to chondrogenic, osteogenic, and adipogenic phenotypes. Emergent features, at days 56 and 70, consisted of chondrogenesis on the surface of hydrogels induced to osteogenic and adipogenic phenotypes. Results indicate that this matrix may be useful for tissue engineering and disease modeling applications.
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Hyaluronic acid and mixtures of hyaluronic acid and chitosan have been extensively used in the growth and construction of neural organoids.
“Similarly, hyaluronic acid and mixtures of hyaluronic acid and chitosan have been extensively used in the growth and construction of neural organoids111–116.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [112]
Cites
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915 · see citing works
Hydrogels as extracellular matrix mimics for 3D cell culture
Tibbitt, M. W., & Anseth, K. S. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22361 · Cited by 2,727 · see citing works
Growth Factors, Matrices, and Forces Combine and Control Stem Cells
Discher, D. E., Mooney, D. J., & Zandstra, P. W. (2009) · Science · doi:10.1126/science.1171643 · Cited by 2,666 · see citing works
CD44 is the principal cell surface receptor for hyaluronate
Aruffo, A. A., Stamenkovic, I., Melnick, M., Underhill, C. B., & Seed, B. (1990) · Cell · doi:10.1016/0092-8674(90)90694-a · Cited by 2,439 · see citing works
Role of the extracellular matrix in regulating stem cell fate
Watt, F. M., & Huck, W. T. S. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3620 · Cited by 861 · see citing works
Neurite branching on deformable substrates
Flanagan, L. A., Ju, Y. S., Marg, B., Osterfield, M., & Janmey, P. A. (2002) · Neuroreport · doi:10.1097/00001756-200212200-00007 · Cited by 759 · see citing works
Hyaluronan: Preparation, Structure, Properties, and Applications
Lapčík, L., Lapčík, L., Smedt, S. C. D., Demeester, J., & Chabreček, P. (1998) · Chemical Reviews · doi:10.1021/cr941199z · Cited by 737 · see citing works
Gerecht, S., Burdick, J. A., Ferreira, L., Townsend, S. A., Langer, R., & Vunjak‐Novakovic, G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703723104 · Cited by 666 · see citing works
Underhill, C. B. (1992) · Journal of Cell Science · doi:10.1242/jcs.103.2.293 · Cited by 617 · see citing works
Chung, C., & Burdick, J. A. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0067 · Cited by 465 · see citing works
Zhu, H., Mitsuhashi, N., Klein, A., Barsky, L. W., Weinberg, K. I., Barr, M. L., Demetriou, A. A., & Wu, G. D. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0186 · Cited by 408 · see citing works
Buxboim, A., Ivanovska, I. L., & Discher, D. E. (2010) · Journal of Cell Science · doi:10.1242/jcs.041186 · Cited by 401 · see citing works
Bian, L., Güvendiren, M., Mauck, R. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214100110 · Cited by 400 · see citing works
Review. Hyaluronan: A Powerful Tissue Engineering Tool
Allison, D. D., & Grande-Allen, K. J. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.2131 · Cited by 400 · see citing works
Khetan, S., & Burdick, J. A. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.07.035 · Cited by 281 · see citing works
Kim, I. L., Khetan, S., Baker, B. M., Chen, C. S., & Burdick, J. A. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.004 · Cited by 249 · see citing works
Denuzière, A., Ferrier, D., Damour, O., et al. (1998) · Biomaterials · doi:10.1016/s0142-9612(98)00036-2 · Cited by 247 · see citing works
Isacke, C. M., & Yarwood, H. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00166-2 · Cited by 242 · see citing works
Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells
Solís, M. A., Chen, Y.-H., Wong, T., Zaiatz-Bittencourt, V., Lin, Y.-C., & Huang, L. L. H. (2012) · Biochemistry Research International · doi:10.1155/2012/346972 · Cited by 207 · see citing works
Denuzière, A. (1996) · Carbohydrate Polymers · doi:10.1016/s0144-8617(96)00035-5 · Cited by 185 · see citing works
Erickson, I. E., Kestle, S. R., Zellars, K. H., Farrell, M. J., Kim, M., Burdick, J. A., & Mauck, R. L. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2012.04.033 · Cited by 183 · see citing works
Engineering three-dimensional cell mechanical microenvironment with hydrogels
Huang, G., Wang, L., Wang, S., Han, Y., Wu, J., Zhang, Q., Xu, F., & Lu, T. J. (2012) · Biofabrication · doi:10.1088/1758-5082/4/4/042001 · Cited by 182 · see citing works
Knudson, C. B. (2003) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.10013 · Cited by 176 · see citing works
Cell Junctions, Cell Adhesion, and the Extracellular Matrix
Alberts, B., Johnson, A., Lewis, J. H., et al. (2007) · Molecular Biology of the Cell · doi:10.1201/9780203833445-19 · Cited by 158 · see citing works
Davidson, L. A., OSTER, G. F., Keller, R. E., et al. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9249 · Cited by 140 · see citing works
Lisignoli, G., Cristino, S., Piacentini, A., Toneguzzi, S., Grassi, F., Cavallo, C., Zini, N., Solimando, L., Maraldi, N. M., & Facchini, A. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.02.031 · Cited by 125 · see citing works
Wu, S., Chang, J., Wang, C., Wang, G., & Ho, M. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.089 · Cited by 117 · see citing works
Hydrogels for in vivo‐like three‐dimensional cellular studies
DeVolder, R. J., & Kong, H. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1174 · Cited by 102 · see citing works
Stoker, M. G. P. (1967) · Journal of Cell Science · doi:10.1242/jcs.2.3.293 · Cited by 101 · see citing works
CD44 modulates Smad1 activation in the BMP-7 signaling pathway
Peterson, R. S., Andhare, R. A., Rousche, K. T., Knudson, W., Wang, W., Grossfield, J. B., thomas, R. O., Hollingsworth, R. E., & Knudson, C. B. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200402138 · Cited by 85 · see citing works
Ragetly, G. R., Griffon, D. J., & Chung, Y. S. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.05.016 · Cited by 84 · see citing works
Yim, E. K. F., Wan, A. C. A., Visage, C. L., et al. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.07.037 · Cited by 71 · see citing works
Ehlers, E., Behrens, P., Wünsch, L., et al. (2001) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/s0940-9602(01)80007-8 · Cited by 64 · see citing works
Goodstone, N. J., Cartwright, A. J., & Ashton, B. A. (2004) · Tissue Engineering · doi:10.1089/107632704323061979 · Cited by 61 · see citing works
The use of a polyelectrolyte fibrous scaffold to deliver differentiated hMSCs to the liver
Tai, B. C. U., Du, C., Gao, S., et al. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.022 · Cited by 56 · see citing works
Defined high protein content surfaces for stem cell culture
Doran, M. R., Frith, J. E., Prowse, A. B. J., et al. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.03.015 · Cited by 34 · see citing works
Isaacs, S. D., Fan, X., Fan, D., Gewant, H. D., Murphy, T. C., FARMER, P. K., Taylor, W. R., Nanes, M. S., & Rubin, J. E. (1999) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199905)179:2 · Cited by 21 · see citing works
Park, K.-H., Kim, S. W., & Bae, Y. H. (2001) · Journal of Biomedical Materials Research · doi:10.1002/1097-4636(200104)55:1 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Chitosan: an update on potential biomedical and pharmaceutical applications.
Cheung, R., Ng, T., Wong, J., & Chan, W. (2015) · Marine Drugs · doi:10.3390/md13085156 · Cited by 1,297 · see citing works
Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
Lindborg, B. A., Brekke, J. H., Vegoe, A. L., Ulrich, C. B., Haider, K. T., Subramaniam, S., Venhuizen, S. L., Eide, C. R., Orchard, P. J., Chen, W., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0305 · Cited by 141 · see citing works
Self-citationPourjabbar, B., Biazar, E., Heidari Keshel, S., & Baradaran‐Rafii, A. (2023) · International Wound Journal · doi:10.1111/iwj.13896 · Cited by 20 · see citing works
- Authors
- Lindborg, B. A., Brekke, J. H., Scott, C. M., Chai, Y. W., Ulrich, C., Sandquist, L., Kokkoli, E., & O'Brien, T. D.
- Affiliations
- University of Minnesota (US)
- Bioactive Regenerative Therapeutics, Inc., Duluth, Minnesota.
- Ascension (US)
- Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota.
- Venue
- Tissue Engineering Part A
- Publisher
- SAGE Publications
- Published
- 2015-06
- Volume
- 21
- Issue
- 11-12
- Pages
- 1952-1962
- ISSN
- 1937-3341 (ISSN-L)
- 1937-335X
- OpenAlex
- W1937223179
- Cited by
- 37
- References
- 38
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Tissue Engineering Part A (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- chitosan, hyaluronic acid, hydrogels, hydrocolloids, 3D cell culture, chondrogenic differentiation, osteogenic differentiation, adipogenesis, tissue engineering scaffolds, disease modeling
- MeSH terms
- Bone Marrow Cells, Cell Differentiation, Colloids, Humans, Hyaluronic Acid, Materials Testing, Microscopy, Electron, Scanning, Osteocytes, Phenotype, Rheology, Viscosity, Adipocytes, Cell Culture Techniques, Chondrocytes, Hydrogels, Tissue Engineering, Chitosan, Elastic Modulus, Mesenchymal Stem Cells, Cellular Microenvironment
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