A1 Refereed original research article in a scientific journal
Functional enzyme delivery via surface-modified mesoporous silica nanoparticles in 3D printed nanocomposite hydrogels
Authors: Mahran, Alaa; Howaili, Fadak; Bhadane, Rajendra; Mathiyalagan, Rathna; Viitala, Tapani; Wang, Xiaoju; Rosenholm, Jessica M.
Publisher: Elsevier BV
Publication year: 2025
Journal: European Journal of Pharmaceutical Sciences
Journal name in source: European Journal of Pharmaceutical Sciences
Article number: 107132
Volume: 211
First page : 107132
ISSN: 0928-0987
eISSN: 1879-0720
DOI: https://doi.org/10.1016/j.ejps.2025.107132
Web address : https://doi.org/10.1016/j.ejps.2025.107132
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/492088495
Three-dimensional (3D) printed hydrogel-based scaffolds have emerged as promising for the delivery of biologicals. Recently, we developed a printable plant-based nanocomposite hydrogel, composed of anionic cellulose nanofibers (T-CNF) and methacrylated galactoglucomannan (GGMMA), reinforced with mesoporous silica nanoparticles (MSNs) of different surface charges. However, ensuring the biological activity of the delivered biomolecules requires further investigation to validate the functionality of the developed biomaterial. To investigate this, in this study, horseradish peroxidase (HRP) and lysozyme were selected as distinct model proteins, assessing their immobilization stability and biological activity after MSN immobilization and 3D printing. The interactions between the enzymes and differently surface-modified MSNs were explored using multi-parametric surface plasmon resonance (MP-SPR) and molecular dynamics (MD) simulations. We observed that MSN surface charge is key to the extent of enzyme adsorption and activity control. Positively charged MSNs showed the highest HRP immobilization but caused significant activity loss in both enzymes. In contrast, near-neutral and negatively charged MSNs provided improved stability and activity retention for HRP and lysozyme, respectively. Except for lysozyme/hydrogel, HRP/hydrogel and enzyme-loaded nanocomposite hydrogels (HRP-loaded near-neutral and lysozyme-loaded negatively charged MSNs) were successfully 3D printed using different UV post-curing times. While enzyme-laden nanocomposite scaffolds showed promising immobilization stability, the presence of the photoinitiator caused significant inactivation for both enzymes. Irrespective of the crosslinking approach, this matrix demonstrates significant potential as a delivery carrier for various biomolecules, with promising applications in tissue engineering and wound healing.
Keywords: Cellulose nanofibers; Hydrogel extrusion 3D printing; MD simulation; Mesoporous silica nanoparticles; Nanocomposite biomaterial; Protein-nanoparticles interaction.
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Funding information in the publication:
Transmission electron microscopy samples were performed at the Electron Microscopy Laboratory, Institute of Biomedicine, University of Turku, and Biocenter Finland. A. Mahran would like to acknowledge the financial support from the Ministry of Higher Education of the Arab Republic of Egypt. X. Wang would like to thank the Research Council of Finland for the Academy Research Fellow project (333158) for her research at ÅAU. The Business Finland co-innovation project “3D Cure” (575/31/2023), PoDoCo, and Swedish cultural foundation (grant number 190913) are acknowledged for funding support. R. Mathiyalagan greatly acknowledges the Åbo Akademi University doctoral research grant and Finnish Pharmaceutical Society research grant. Dhayakumar Rajan Prakash and Tomi Kalpio from Brinter AM Technologies Ltd (Turku, Finland) are acknowledged for kind support to technical perspectives of operating the Brinter ONE 3D BioPrinter. This research is also aligned with the strategic research profiling area “Solutions for Health” at Åbo Akademi University (funded by the Research Council/Academy of Finland, 336355) and parts of the research used the Research Council of Finland Research Infrastructure “Printed Intelligence Infrastructure” (PII-FIRI). R. Bhadane wish to acknowledge CSC–IT Center for Science, Finland, for generous computational resources.