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Porous cellulose-collagen scaffolds for soft tissue regeneration: influence of cellulose derivatives on mechanical properties and compatibility with adipose-derived stem cells

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Abstract

This study compares two types of bioresorptive cellulose, i.e., calcium-sodium salt of oxidized cellulose (OC) and sodium salt of carboxymethylcellulose (CMC). It investigates which type would be preferable as an implant material in terms of biocompatibility, biomechanical and biological properties, and also in terms of its behavior in combination with collagen fibrils (Col) in composite Col/OC or Col/CMC scaffolds. OC significantly supported the stiffness and elasticity of Col fibrils, whereas CMC significantly reduced these properties. OC also enabled a strong interaction with Col fibrils even in a moist environment, accompanied by a significant drop in elastic modulus. The addition of cellulose did not significantly influence scaffold porosity; however, changes in surface morphology and the lower swelling capacity of OC, with a degree of oxidation of its chains between 16 and 24%, supported the idea of improved cell-material interaction. The elasticity and the stiffness of Col/OC guided human adipose-derived stem cells (hADSCs) to significantly higher adhesion, proliferation, and metabolic activity. On the contrary, the Col/CMC provided only limited mechanical support for the cells and inhibited their attachment and proliferation, although without any signs of cytotoxicity. This phenomenon could be used for future control of the differentiation of hADSCs towards a desired phenotype to generate advanced tissue replacements using modern methods of tissue engineering. The oxidation of cellulose resulted in a firmer scaffolding material, as required in vascular or skin tissue engineering. CMC is suitable for moist wound healing, e.g. as a mucoadhesive gel, where cell adhesion is not desirable.

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Acknowledgments

We thank Petr Lepcio for useful consultations on charge density and for correcting the biomechanical aspects of this paper, and Zuzana Kadlecová for measurement of Zeta potential. CzechNanoLab project LM2018110 funded by MEYS CR is gratefully acknowledged for the financial support for measurements/sample fabrication at CEITEC Nano Research Infrastructure. Mr. Robin Healey (Czech Technical University, Prague) is gratefully acknowledged for his language revision of the manuscript.

Funding

The material aspects of this work were supported by the Ministry of Health of the Czech Republic under project no. NV 19-0500214, and the biological aspects were supported by the Czech Science Foundation (Grant No. 20-01641S). All rights reserved. We acknowledge the Light Microscopy Core Facility, IMG CAS, Prague, Czech Republic, supported by MEYS (LM2018129, CZ.02.1.01/0.0/0.0/18_046/0016045) and RVO: 68378050-KAV-NPUI, for their support with the confocal image analysis presented here.

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by KK, MT, JP and MK. SEM pictures were provided by KH. Material preparation for biological analysis is attributed to JD. Confocal microscopy photography and analysis provided MT. Methodology and supervision is attributed to LV from the material part and LB from the biological part. The first draft of the manuscript was written by KK. Authors who commented on previous versions of the manuscript and did additional changes: MT, JD. Who critically reviewed the manuscript LB and LV. PP reviewed its mechanical part. Funding acquisition: LV, LB. All authors read and approved the final manuscript. All authors read and approved the final manuscript.

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Correspondence to Lucy Vojtová.

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Kacvinská, K., Trávníčková, M., Vojtová, L. et al. Porous cellulose-collagen scaffolds for soft tissue regeneration: influence of cellulose derivatives on mechanical properties and compatibility with adipose-derived stem cells. Cellulose 29, 8329–8351 (2022). https://doi.org/10.1007/s10570-022-04759-4

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