3DLife

• Stahl, Margrethe Cecilie; Bergendahl, K.G.; Zaytseva-Zotova, Daria; Rytterager, K.R.; Nordgård, Catherine Taylor & Kjesbu, Joachim Sebastian [Show all 11 contributors for this article] (2026). RGD-Alginate beads as scaffolds for culturing primary human dermal and pulmonary fibroblasts. Carbohydrate Polymers. ISSN 0144-8617. 379, p. 1–10. doi: 10.1016/j.carbpol.2026.124913. Full text in Research Archive Show summary

  The use of hydrogel microparticles as granular hydrogels is an emerging approach in tissue engineering, where microparticles offer printability, injectability, and serve as scaffolds for cell culture. While culturing dermal fibroblasts for tissue engineering applications is well reported, there is limited research on culturing primary human pulmonary fibroblasts on granular hydrogels. In this study, we grafted RGD-peptides to alginate, formed microbeads, and investigated the ability of granular hydrogels to support the adhesion and growth of primary normal human dermal fibroblasts (NHDFs) and human pulmonary fibroblasts (HPFa). NHDFs adhered to linear RGD (linRGD)-alginate microbeads and spread on the bead surfaces with increased adhesion with increased peptide concentration (0.3–1.3 mM). In contrast, HPFa did not adhere to the linRGD-alginate microbeads. However, HPFa adhered and spread on flat linRGD-alginate gels, indicating that HPFa do respond to linRGD as an adhesion ligand. Supplementation of resulted in cell adhesion to linRGD-alginate microbeads. Enhanced adhesion and spreading of HPFa to RGD-alginate microbeads were observed when using cyclic RGD. Hence, RGD-alginate microbeads is a promising material for structuring primary human dermal and pulmonary fibroblasts, showing the relevance of using alginate microbeads as scaffolds for 3D cultures with fibroblasts.

• Solbu, Anita Akbarzadeh; Caballero, David; Damigos, Spyridon; Kundu, Subhas C.; Reis, Rui L. & Halaas, Øyvind [Show all 8 contributors for this article] (2023). Assessing cell migration in hydrogels: An overview of relevant materials and methods. Materials Today Bio. 18. doi: 10.1016/j.mtbio.2022.100537. Full text in Research Archive Show summary

  Cell migration is essential in numerous living processes, including embryonic development, wound healing, immune responses, and cancer metastasis. From individual cells to collectively migrating epithelial sheets, the locomotion of cells is tightly regulated by multiple structural, chemical, and biological factors. However, the high complexity of this process limits the understanding of the influence of each factor. Recent advances in materials science, tissue engineering, and microtechnology have expanded the toolbox and allowed the development of biomimetic in vitro assays to investigate the mechanisms of cell migration. Particularly, three-dimensional (3D) hydrogels have demonstrated a superior ability to mimic the extracellular environment. They are therefore well suited to studying cell migration in a physiologically relevant and more straightforward manner than in vivo approaches. A myriad of synthetic and naturally derived hydrogels with heterogeneous characteristics and functional properties have been reported. The extensive portfolio of available hydrogels with different mechanical and biological properties can trigger distinct biological responses in cells affecting their locomotion dynamics in 3D. Herein, we describe the most relevant hydrogels and their associated physico-chemical characteristics typically employed to study cell migration, including established cell migration assays and tracking methods. We aim to give the reader insight into existing literature and practical details necessary for performing cell migration studies in 3D environments.

• Hesjedal, Maria Bårdsen (2022). Socializing Scientists into Interdisciplinarity by Placemaking in a Multi-sited Research Center. Science, Technology and Human Values. ISSN 0162-2439. doi: 10.1177/01622439221100867. Full text in Research Archive
• Arlov, Øystein; Rütsche, Dominic; Korayem, Maryam Asadi; Öztürk, Ece & Zenobi-Wong, Marcy (2021). Engineered Sulfated Polysaccharides for Biomedical Applications. Advanced Functional Materials. ISSN 1616-301X. 31(19), p. 1–52. doi: 10.1002/adfm.202010732. Full text in Research Archive Show summary

  Sulfated polysaccharides are ubiquitous in living systems and have central roles in biological functions such as organism development, cell proliferation and differentiation, cellular communication, tissue homeostasis, and host defense. Engineered sulfated polysaccharides (ESPs) are structural derivatives not found in nature but generated through chemical and enzymatic modification of natural polysaccharides, as well as chemically synthesized oligo- and polysaccharides. ESPs exhibit novel and augmented biological properties compared with their unmodified counterparts, mainly through facilitating interactions with other macromolecules. These interactions are closely linked to their sulfation patterns and backbone structures, providing a means to fine-tune biological properties and characterize structural–functional relationships by employing well-characterized polysaccharides and strategies for regioselective modification. The following review provides a comprehensive overview of the synthesis and characterization of ESPs and of their biological properties. Through the pioneering research presented here, key emerging application areas for ESPs, which can lead to novel breakthroughs in biomedical research and clinical treatments, are highlighted.

• Omtvedt, Line Aanerud; Kristiansen, Kåre Andre; Strand, Wenche Iren; Aachmann, Finn Lillelund; Strand, Berit Løkensgard & Zaytseva-Zotova, Daria (2021). Alginate hydrogels functionalized with β-cyclodextrin as a local paclitaxel delivery system. Journal of Biomedical Materials Research. Part A. ISSN 1549-3296. 109(12), p. 2625–2639. doi: 10.1002/jbm.a.37255. Full text in Research Archive Show summary

  Modification of drug delivery materials with beta-cyclodextrins (β-CyD) is known to increase solubility of poorly water-soluble drugs, protect drugs from degradation and sustain release. In this study, we developed a hydrogel drug delivery system for local paclitaxel delivery using the natural polysaccharide alginate functionalized with β-CyD-moieties. Paclitaxel was chosen due to its ability to form inclusion complexes with cyclodextrins. The rheological and mechanical properties of the prepared hydro- gels were characterized, as well as in vitro release of the paclitaxel and in vitro activ- ity on PC-3 prostate cancer cells. Introduction of β-CyD-moieties into the hydrogel reduces the mechanical properties of the gels compared to nonmodified gels. How- ever, gelation kinetics were not markedly different. Furthermore, the β-CyD-modified alginate helped to reduce undesired crystallization of the paclitaxel in the gel and facilitated paclitaxel diffusion out of the gel network. Remarkably, the β-CyD grafted alginate showed increased capacity to complex paclitaxel compared to free HPβ- CyD. Release of both paclitaxel and degradation products were measured from the gels and were shown to have cytotoxic effects on the PC-3 cells. The results indicate that functionalized alginate with β-CyDs has potential as a material for drug delivery systems.

• Akbarzadeh, Anita; Koernig, Andre; Kjesbu, Joachim Sebastian; Zaytseva-Zotova, Daria; Sletmoen, Marit & Strand, Berit Løkensgard (2021). High resolution imaging of soft alginate hydrogels by atomic force microscopy. Carbohydrate Polymers. ISSN 0144-8617. 276. doi: 10.1016/j.carbpol.2021.118804. Full text in Research Archive
• Victoria, Moreno-Manzano; Zaytseva-Zotova, Daria; López-Mocholí, Eric; Briz-Redón, Álvaro; Strand, Berit Løkensgard & Serrano-Aroca, Angel (2020). Injectable Gel Form of a Decellularized Bladder Induces Adipose-Derived Stem Cell Differentiation into Smooth Muscle Cells In Vitro. International Journal of Molecular Sciences. ISSN 1661-6596. 21(8608), p. 1–14. doi: 10.3390/ijms21228608. Full text in Research Archive Show summary

  Biologic scaffolds composed of extracellular matrix components have been proposed to repair and reconstruct a variety of tissues in clinical and pre-clinical studies. Injectable gels can fill and conform any three-dimensional shape and can be delivered to sites of interest by minimally invasive techniques. In this study, a biological gel was produced from a decellularized porcine urinary bladder by enzymatic digestion with pepsin. The enzymatic digestion was confirmed by visual inspection after dissolution in phosphate-buffered saline solution and Fourier-transform infrared spectroscopy. The rheological and biological properties of the gel were characterized and compared to those of the MatrigelTM chosen as a reference material. The storage modulus G’ reached 19.4 ± 3.7 Pa for the 30 mg/mL digested decellularized bladder gels after ca. 3 h at 37 °C. The results show that the gel formed of the porcine urinary bladder favored the spontaneous differentiation of human and rabbit adipose-derived stem cells in vitro into smooth muscle cells to the detriment of cell proliferation. The results support the potential of the developed injectable gel for tissue engineering applications to reconstruct for instance the detrusor muscle part of the human urinary bladder.

• Dalheim, Marianne Øksnes; Omtvedt, Line Aanerud; Bjørge, Isabel M.; Akbarzadeh, Anita; Mano, Joao F. & Aachmann, Finn Lillelund [Show all 7 contributors for this article] (2019). Mechanical Properties of Ca-Saturated Hydrogels with Functionalized Alginate. Gels. 5(2), p. 1–19. doi: 10.3390/gels5020023. Full text in Research Archive Show summary

  In this work, the mechanical properties and stability of alginate hydrogels containing functionalized alginates (peptide and β-cyclodextrin) were studied. There is an increasing interest in the modification of alginates to add functions such as cell attachment and increased solubility of hydrophobic drugs, for better performance in tissue engineering and drug release, respectively. Functionalization was achieved in this study via periodate oxidation followed by reductive amination, previously shown to give a high and controllable degree of substitution. Young’s modulus and the stress at rupture of the hydrogels were in general lowered when exchanging native alginate with the modified alginate. Still, the gel strength could be adjusted by the fraction of modified alginate in the mixed hydrogels as well as the degree of oxidation. No notable difference in deformation at rupture was observed while syneresis was influenced by the degree of oxidation and possibly by the nature and amount of the grafted molecules. The mixed hydrogels were less stable than hydrogels with only native alginate, and modified alginate was released from the hydrogels. Furthermore, the hydrogels in general rather disintegrated than swelled upon saline treatments.

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• Zaytseva-Zotova, Daria; Haslene-Hox, Hanne; Arlov, Øystein; Hoel, Andrea Draget; Mjelle, Robin & Strand, Wenche [Show all 13 contributors for this article] (2023). Alginate hydrogel characteristics regulate NHDF biology. Full text in Research Archive
• Haslene-Hox, Hanne; Chahal, Aman Singh; Arlov, Øystein; Øynebråten, Ingrid Ryge; Zaytseva-Zotova, Daria & Vikenes, Anette [Show all 16 contributors for this article] (2023). Alginate hydrogel characteristics regulate fibroblast biology. Full text in Research Archive
• Chahal, Aman S; Strand, Berit Løkensgard; Haslene-Hox, Hanne & Sætrom, Pål (2022). An out of body experience: Cell culture in 3D. Full text in Research Archive Show summary

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• Hoven, Sigrid Setsaas; Haslene-Hox, Hanne; Chahal, Aman S; Goksøyr, Anders; Routti, Heli Anna Irmeli & Strand, Berit Løkensgard (2022). Establishing robust 2D cultures of killer whale primary cells: an optimization study. Full text in Research Archive
• Strand, Berit Løkensgard (2021). Enzymatic and chemical tailoring of alginates hydrogels for biomedical applications. Full text in Research Archive
• Zaytseva-Zotova, Daria; Haslene-Hox, Hanne; Arlov, Øystein; Vikenes, Anette; Hoel, Andrea Draget & Chahal, Aman S [Show all 15 contributors for this article] (2021). Alginate Hydrogel Characteristics Regulate Dermal Fibroblasts Biology. Full text in Research Archive
• Zaytseva-Zotova, Daria; Haslene-Hox, Hanne; Arlov, Øystein; Vikenes, Anette; Hoel, Andrea Draget & Chahal, Aman S [Show all 13 contributors for this article] (2020). Varying single parameters of the alginate hydrogels to design better microenvironments for fibroblasts cultivation in vitro. Full text in Research Archive
• Seres, Silvija & Strand, Berit Løkensgard (2019). #152: Vev-på-chip. [Internet]. LØRN.TECH (podcast). Full text in Research Archive
• Zaytseva-Zotova, Daria; Ruohola, Rita; Strand, Wenche Iren; Akbarzadeh, Anita; Haslene-Hox, Hanne & Arlov, Øystein [Show all 12 contributors for this article] (2019). Soft alginate hydrogels modified with bioactive peptides as extracellular matrices for 3D fibroblast culture. Full text in Research Archive
• Hoel, Andrea Draget; Haslene-Hox, Hanne; Arlov, Øystein; Klinkenberg, Geir; Vikenes, Anette & Åslund, Andreas [Show all 11 contributors for this article] (2019). 3DLife: Validating new high-throughput methods for 3D cell culture screening. Full text in Research Archive
• Zaytseva-Zotova, Daria; Ruohola, Rita; Strand, Wenche Iren; Akbarzadeh, Anita; Haslene-Hox, Hanne & Arlov, Øystein [Show all 14 contributors for this article] (2019). Alginate hydrogels with tailored mechanical and biological properties for 3D fibroblast culture. Full text in Research Archive
• Zaytseva-Zotova, Daria; Strand, Wenche Iren; Akbarzadeh, Anita; Rouhola, Rita; Haslene-Hox, Hanne & Arlov, Øystein [Show all 11 contributors for this article] (2019). Optimizing alginate gelation conditions for 3D cell culture. Full text in Research Archive
• Strand, Berit Løkensgard (2019). Alginate enzymatic and chemical modification and their use in biomedical applications. Full text in Research Archive
• Arlov, Øystein; Haslene-Hox, Hanne; Eikenes, Åsmund H.; Carlsen, Sven Magnus & Aksnes, Astrid (2018). Tett på livet med digital forskning. Full text in Research Archive
• Brautaset, Trygve; Strand, Berit Løkensgard & Tarjem, Guro (2018). Utfordringer for bioteknologien. Full text in Research Archive
• Haslene-Hox, Hanne; Arlov, Øystein; Vikenes, Anette; Hoel, Andrea Draget; Klinkenberg, Geir & Strand, Wenche Iren [Show all 8 contributors for this article] (2018). 3D cell culture: Tailoring matrix properties for cell culture and high throughput screening. Full text in Research Archive Show summary

  Introduction: Alginate, a linear polysaccharide from seaweed, is used both in food and in biomedical applications. The low toxicity and immunogenicity together with the ability to form hydrogels at physiological conditions makes them attractive scaffolds in tissue engineering. In this first part of the 3DLife project, we have tailored alginate gel kinetics, mechanical properties and gel dissolution to be relevant for soft tissue engineering, 96-wellplate format and robotic handling. Methods: Alginate gelation kinetics and mechanical properties was controlled by using the slowly hydrolysing glucono-δ-lactone (GDL) together with CaCO3 and citrate buffer. The gelation was followed on a Kinexus Rheometer and gel elasticity measured as storage modulus (G´). Fibroblasts (IMR90) was mixed with citrate buffer, alginate and CaCO3 before the addition of GDL and culture media was added 2 hrs after gelation. Different cell concentrations, alginate concentrations and viability assays were evaluated over a culture period for 72 hours. Results and Discussion: Alginate hydrogel mechanical properties (G´) was controlled by increasing alginate concentrations and CaCO3 and GDL accordingly (Figure 1A). This gives plateau values of storage modulus of 100 and 800 Pa for 0.5% alginate and 1.0% alginate, respectively, which is within the relevant range of soft tissue previously shown for gels of PEG and hyaluronic acid. Cell encapsulation and culture conditions were optimised for robotic handling and culture in 96-wellplate format. Preliminary results show cells with different morphology in the hydrogels of 0.5% and the 1.0% alginate, indicating sensitivity towards mechanical properties (Figure 1B and C). The hydrogels could easily be dissolved within 30 to 140 seconds and cell retrieved by adding a calcium-chelating buffer. This is important for the further and detailed analyses of the cell transcriptome under tailored conditions in their microenvironment.

• Halaas, Øyvind; Sætrom, Pål; Arlov, Øystein; Haslene-Hox, Hanne; Beisvag, Vidar & Aachmann, Finn Lillelund [Show all 10 contributors for this article] (2018). 3DLife – Emulating life in 3D with digital and experimental tissue models. Full text in Research Archive
• Strand, Berit Løkensgard (2018). Tissue engineering with hydrogels – building 3D tissue structures with alginate. Full text in Research Archive
• Zaytseva-Zotova, Daria; Strand, Wenche Iren; Akbarzadeh, Anita; Haslene-Hox, Hanne; Arlov, Øystein & Vikenes, Anette [Show all 10 contributors for this article] (2018). Alginate-based biomimetic matrices for 3D cell culture and high throughput screening. Full text in Research Archive

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