Emulating life in 3D with digital and experimental tissue models.
During 2020, our research focused on the RNA screening of human dermal fibroblasts when cultured in different hydrogels. Our results show that there are major differences in gene expression when the cells are cultured on normal plastic surfaces (2D) and within the hydrogels (3D). We are now studying the differences in gene expression depending on material stiffness and the content of biologically active molecules within the materials. The RNA screen data is also compared to published data on fibroblasts from different tissue. We have also started to structure the hydrogels and culture cells on both surfaces and within hydrogel materials with profiles in their densities and structural components.
One highlight of 2020 has been showing that we can maintain the viability and morphological features of fibroblasts in 3D cultures for more than 50 days, and that the fibroblasts like soft materials and respond in a controlled way by morphological changes to biological signals as well as structural elements within the gels, as can be seen in the figure.
For us, the added value of being a part of a transdisciplinary centre is learning from other projects and collaboration on common interests. This year we have collaborated with the dCod project. The culture of liver tissue in the hydrogels was not successful, but whale fibroblasts responded well to morphological changes in the hydrogels.
Scientific publications 2020: 1
3DLife: Validating new high-throughput methods for 3D cell culture screening (2019)
Andrea Draget Hoel, Hanne Haslene-Hox, Øystein Arlov, Geir Klinkenberg, Anette Vikenes, Andreas Åslund, Wenche I. Strand, Anita Akbarzadeh, Daria Zaytseva-Zotova, Berit Løkensgard Strand, Håvard Sletta
Alginate hydrogels with tailored mechanical and biological properties for 3D fibroblast culture (2019)
Daria Zaytseva-Zotova, Rita Ruohola, Wenche Iren Strand, Anita Akbarzadeh, Hanne Haslene-Hox, Øystein Arlov, Anette Vikenes, Andrea Draget Hoel, Øyvind Halaas, Pål Sætrom, Geir Klinkenberg, Finn Lillelund Aachmann, Håvard Sletta, Berit Løkensgard Strand
Optimizing alginate gelation conditions for 3D cell culture (2019)
Daria Zaytseva-Zotova, Wenche Iren Strand, Anita Akbarzadeh, Rita Rouhola, Hanne Haslene-Hox, Øystein Arlov, Anette Vikenes, Andrea Draget Hoel, Geir Klinkenberg, Håvard Sletta, Berit Løkensgard Strand
Soft alginate hydrogels modified with bioactive peptides as extracellular matrices for 3D fibroblast culture (2019)
Daria Zaytseva-Zotova, Rita Ruohola, Wenche Iren Strand, Anita Akbarzadeh, Hanne Haslene-Hox, Øystein Arlov, Anette Vikenes, Andrea Draget Hoel, Geir Klinkenberg, Finn Lillelund Aachmann, Håvard Sletta, Berit Løkensgard Strand
Alginate enzymatic and chemical modification and their use in biomedical applications (2019)
Berit Løkensgard Strand
Mechanical Properties of Ca-Saturated Hydrogels with Functionalized Alginate (2019)
Marianne Øksnes Dalheim, Line Aanerud Omtvedt, Isabel M. Bjørge, Anita Akbarzadeh, Joao F. Mano, Finn Lillelund Aachmann, Berit Løkensgard Strand
#152: Vev-på-chip (2019)
Tissue engineering with hydrogels – building 3D tissue structures with alginate (2018)
Berit Løkensgard Strand
Alginate-based biomimetic matrices for 3D cell culture and high throughput screening (2018)
Daria Zaytseva-Zotova, Wenche Iren Strand, Anita Akbarzadeh, Hanne Haslene-Hox, Øystein Arlov, Anette Vikenes, Anette Draget Hoel, Geir Klinkenberg, Finn Lillelund Aachmann, Berit Løkensgard Strand
Cell culture-based experiments are important pillars in all medically related research, allowing examination of living cells without the use of research animals or human subjects. However, the commonly used cellular monolayer cultures are a remote reflection of in vivo conditions, due to a lack of the cellular, structural and chemical elements forming the tissue microenvironment. This disparity results in cells losing their tissue-like phenotype over time, limiting the potential of the models for studying tissue biology and disease progression, and for testing pharmaceutic and toxic compounds.
3DLife aims to develop novel strategies for microtissue engineering in 3D, to provide model systems of organ function and bridge the gap to in vivo conditions. To understand how the microenvironment affects cells we will synthesize novel and tuneable extracellular scaffold materials, and develop tools for high-throughput screening (HTS) of 3D cell cultures to assess genetic expression patterns in response to defined scaffold properties. These advances have limited translational potential without a digital approach that can process the vast data output from HTS analyses and provide a systems-level understanding of material-cell interactions. By applying a computational model, we can predict the requirements of organotypic cells to their microenvironment and tailor materials for improved in vivo-like tissue and organ models for research and clinical applications beyond the state of the art. To achieve this ambitious goal, 3DLife brings in expert competence within material engineering, high-throughput analyses, transcriptomics and bioinformatics, cell biology and cultivation, microsystem technology and mathematical and computational modelling from NTNU and SINTEF supported by international academic collaboration. The project will contribute to the Centre for Digital Life Norway (DLN) with new knowledge, materials and methodology with a broad field of application in biotechnology.