Interactions between Cells and Bio- based materials: from Quantitative Analysis to 3D-printed Scaffolds for Medical Applications

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School of Chemical Technology | Doctoral thesis (article-based)
Degree programme
76 + app. 112
Aalto University publication series DOCTORAL DISSERTATIONS, 211/2020
The aim of this thesis work was to understand the interactions between plant-derived cellulose nanofibrils (CNF) and human living cells and to apply this knowledge to develop 3D printed scaffolds. These 3D scaffolds have the potential in solving organ crisis issues and replacing animal models for drug screening. A protocol to use colloidal probe microscopy (CPM), a technique based on atomic force microscopy, to easure the interactions between biomaterials (CNF and laminin 521) and living cells as successfully established. Both hepatocellular carcinoma cell line HepG2 and human pluripotent stem cell line WAo7 were studied. It was found that, in contrast to the strong adhesion between laminin and living cells, CNF demonstrated a lower affinity for both HepG2 cells and WAo7 cells. It was moreover found that the interaction between laminin 521 and cells was integrin regulated, while the interaction between CNF and cells was nonspecific and not mediated by integrins. Furthermore, correlation a found between the adhesion energy and successful two- dimensional (2D) cell culture results. Neither HepG2 cells nor WAo7 cells grew on CNF films, but on the laminin 521 films, indicating that a certain magnitude of adhesion energy is required to induce cell growth. Surface plasmon resonance (SPR) was applied in order to further investigate the effect of laminin and another commonly used protein, poly-l-lysine (PLL), as well as other cell culture components, on cell affinity for CNF films. Coating CNF with either laminin 521 or PLL was found to significantly enhance the cell adsorption. To build CNF-based, three-dimensional (3D) cell culture models, 3D printing technique was used to fabricate 3D scaffolds. The combination of, on the one hand, highly charged TEMPO-CNF and galactoglucomannan methacrylates (GGMMAs), and, on the other hand, native, low-charged CNF and alginate together with spherical colloidal lignin particles (CLPs) were both investigated. The TEMPO-CNF/GGMMAs scaffolds exhibited a wide mechanical strength range depending on the degree of crosslinking, which could be controlled by changing the amount and the degree of substitution of GGMMA. On the other hand, CLPs were able to increase the printing resolution and add antioxidant properties to the CNF-alginate-CLPs scaffolds. Both the TEMPO-CNF/GGMMAs and the CNF-alginate-CLPs scaffolds demonstrated excellent shape fidelity and biocompatibility, indicating great potential in biomedical applications.
Supervising professor
Österberg, Monika, Prof., Department of Bioproducts and Biosystems, Aalto University, Finland
Thesis advisor
Valle Delgado, Juan José, Dr., Department of Bioproducts and Biosystems, Aalto University, Finland
bio-based materials, interaction, cellulose nanofibrils, living cells, atomic force spectroscopy, surface plasmon resonance, 3D scaffolds
Other note
  • [Publication 1]: Robertus Wahyu N. Nugroho, Riina Harjumäki, Xue Zhang, Yan-Ru Lou, Marjo Yliperttula, Juan José Valle-Delgado, and Monika Österberg. "Quantifying the interactions between biomimetic biomaterials –collagen I, collagen IV, laminin 521 and cellulose nanofibrils– by colloidal probe microscopy." Colloids and Surfaces B: Biointerfaces 173 (2019): 571-580.
    Full text in Acris/Aaltodoc:
    DOI: /10.1016/j.colsurfb.2018.09.073 View at publisher
  • [Publication 2]: Riina Harjumäki, Robertus Wahyu N. Nugroho, Xue Zhang, Yan-Ru Lou, Marjo Yliperttula, Juan José Valle-Delgado, and Monika Österberg. "Quantified forces between HepG2 hepato- carcinoma and WA07 pluripotent stem cells with natural biomaterials correlate with in vitro cell behavior." Scientific Reports 9, no. 1 (2019): 1-14.
    Full text in Acris/Aaltodoc:
    DOI: 10.1038/s41598-019-43669-7 View at publisher
  • [Publication 3]: Riina Harjumäki, Xue Zhang, Robertus Wahyu N. Nugroho, Muhammad Farooq, Yan-Ru Lou, Marjo Yliperttula, Juan José Valle-Delgado, and Monika Österberg. "AFM Force Spectroscopy Reveals the Role of Integrins and Their Activation in Cell–Biomaterial Interactions." ACS Applied Bio Materials 3, no. 3 (2020): 1406-1417.
    DOI: 10.1021/acsabm.9b01073 View at publisher
  • [Publication 4]: Xue Zhang, Alma Kartal-Hodzic, Riina Harjumäki, Tapani Viitala, Juan José Valle-Delgado, and Monika Österberg. ”Interaction of HepG2 Cells with Cellulose Nanofibril (CNF) film Detected by Surface Plasmon Resonance (SPR).” Manuscript submitted to Journal of Colloid and Interface Science
  • [Publication 5]: Wenyang Xu, Xue Zhang, Peiru Yang, Otto Långvik, Xiaoju Wang, Yongchao Zhang, Fang Cheng, Monika Österberg, Stefan Willför, and Chunlin Xu. "Surface engineered biomimetic inks based on UV cross-linkable wood biopolymers for 3D printing. "ACS Applied Materials & Interfaces 11, no. 13 (2019): 12389-12400.
    DOI: 10.1021/acsami.9b03442 View at publisher
  • [Publication 6]: Xue Zhang, Maria Morits, Christopher Jonkergouw, Ari Ora, Juan José Valle-Delgado, Muhammad Farooq, Rubina Ajdary, Siqu Huan, Markus Linder, Orlando Rojas, Mika Henrikki Sipponen, and Monika Österberg. "Three-Dimensional Printed Cell Culture Model Based on Spherical Colloidal Lignin Particles and Cellulose Nanofibril-Alginate Hydrogel. Biomacromolecules, vol. 21, no 5 pp.1875-1885.
    DOI: 10.1021/acs.biomac.9b01745 View at publisher