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Crosslinked oxidized-nanocellulose/chitosan hydrogels as a scaffold matrix for mesenchymal stem cell growth

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Abstract

Mesenchymal stem cells (MSC) are recognized for their immunomodulatory effects and regenerative properties, being promising therapeutic agents for a wide range of diseases. To ensure a localized effect of MSC in the organism biobased hydrogels have been tested for their ability to act as a matrix-embedded to improve MSC targeted delivery. In this context, nanocellulose (NC) has been used for drug delivery, showing biocompatibility and durability in time, but until now NC has not been tested for MSC growth exploiting the size and aldehyde content of NC. In this study, cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and microfibrillated cellulose (MFC) were studied after one-pot oxidation and further crosslinking with chitosan (mass ratio 1:5). Size and aldehyde content of oxidized NC samples were evaluated to analyze their influence on the hydrogel’s properties. The crosslinked hydrogels were analyzed by FESEM, swelling ability, FTIR, compression tests, thermal stability, and stability in culture cell conditions. Oxidized-MFC hydrogel improved the mechanical stability and swelling behavior, but it lacks stability at cell conditions possibly due to its low aldehyde content (0.54 mmol/g). Conversely, oxidized CNF and oxidized CNC formed suitable crosslinked hydrogels for cell adhesion, and for growing and proliferating of MSC 3D spheroids after 120 h. However, only hydrogel with PO-CNF/chitosan shows antibacterial activity as well as MSC proliferation.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgments

The authors would like to express their gratitude to the financial support given by the Agencia Nacional de Investigación y Desarrollo (ANID), FONDECYT project 3220462 and the funding contribution of ECOS220020 project. R.S.R. thanks to FONDEQUIP grant EQM190179, J. L. C wishes to thank the financial support given by the University of Bío-Bío for his internal PhD scholarship granted, P. P thanks to FONDECYT project 1220416 and G. C thanks to FONDECYT regular 1221609.

Funding

This research was supported by Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT ID 3220462).

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Conceived the structure of the article, M.A.M; conceptualization, MAM, KO, AA; methodology, MAM, CT, AA, MS, KO, JLC, RS, MGP; Formal analysis, MAM, KO; investigation, MAM, KO; resources, MS, PP, JN, GC, RS; JC, writing-original draft preparation, MAM, KO, supervision, KO, JC. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Mayra A. Mariño or Johanna Castaño.

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The authors declare that they have no conflict of interest.

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Ethical approval for this study was obtained from “Directorate of Integrity, Safety and Research Ethics of the Vice-Rector for Research and Doctorates of the Universidad San Sebastián” to commencing the study and performed in accordance with relevance institutional and national guidelines and regulations of CONICYT-2018 (certificate CB-22–003).

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Mariño, M.A., Oyarce, K., Tobar, C. et al. Crosslinked oxidized-nanocellulose/chitosan hydrogels as a scaffold matrix for mesenchymal stem cell growth. Cellulose 31, 363–379 (2024). https://doi.org/10.1007/s10570-023-05591-0

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  • DOI: https://doi.org/10.1007/s10570-023-05591-0

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