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Cellulose-in-cellulose 3D-printed hydrogels and aerogels for soft tissue engineering
* 1, 2, 3 , 1 , 2 , 3, 4 , 1 , 1
1  Institute of Materials Science of Barcelona, ICMAB-CSIC, Campus UAB, 08193 Bellaterra, Spain.
2  Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, iMATUS and Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
3  Research Institute for Medicines (iMed. ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, Lisbon 1649-003, Portugal.
4  Institute of Biophysics and Biomedical Engineering (IBEB), Faculty of Sciences, University of Lisbon, Campo Grande, Lisbon 1749-016, Portugal.
Academic Editor: SIDI A. BENCHERIF

Abstract:

Introduction

Bacterial cellulose is one of the cellulose derivatives with the greatest purity and porosity, so it has sparked interest in the regenerative medicine field [1]. Nevertheless, the addition of bacterial cellulose nanofibers modifies the rheological properties of 3D printing inks, so certain applications of nanocellulose as part of 3D-printed gels have barely been explored.

Methodology

In this work, bacterial cellulose nanofibers are obtained through a well-established protocol from the bacterial strain K. xylinus [1 - 3] and were added into methylcellulose inks to manufacture 3D-printed hydrogels and aerogels. Polyurea crosslinking was explored as a method to enhance the performance of the cellulose-in-cellulose gels. Scanning and transmission electron microscopies as well as printing fidelity measurements were employed to characterize the gels. Cell studies and hemolytic activity tests were conducted to ensure the absence of toxicity of the formulations.

Results and Discussion

Bacterial cellulose nanofibers were obtained with a diameter close to 50 nm and were incorporated into methylcellulose inks, with shear-thinning properties adequate for 3D printing. Nanocellulose added into gels decreased their volume shrinkage and increased their printing fidelity. Polyurea crosslinking yielded biocompatible gels with enhanced structural properties. The results obtained encourage future research on these gels as soft tissue grafts.

Conclusions

Bacterial cellulose nanofibers were incorporated into 3D-printed methylcellulose hydrogels and aerogels, yielding structures with morphological properties suitable for soft tissue engineering. The polyurea crosslinking of the cellulose-in-cellulose gels enhanced their physicochemical performance, resulting in promising formulations for regenerative medicine.

Acknowledgments

This work was funded by MICIU/AEI/10.13039/501100011033 [grants PID2023-151340OBI00, PDC2022-133526-I00, and PDC2023-145826-I00], Xunta de Galicia [ED431C2022/2023], ERDF/EU, and European Union NextGenerationEU/PRTR. A. I.-M. acknowledges Xunta de Galicia for her postdoctoral fellowship [ED481B-2025/032].

References

[1] Malandain N et al, 2023, 10.1021/acsabm.3c00126.

[2] Iglesias-Mejuto et al, 2024, 10.1007/s10570-023-05601-1.

[3] Iglesias-Mejuto et al, 2025, 10.1021/acsami.5c08389.

Keywords: Hydrogels; Aerogels; Bacterial cellulose nanofibers; Soft tissue engineering; Regenerative medicine
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