Anne Eriksson Agger

• Småland-Reksten, Agnes; Agger, Anne Eriksson; Lian, Aina-Mari; Reseland, Janne Elin & Krüger, Tormod Bjartveit (2026). Bisphosphonate and statin: adverse effects of co-medication on wound healing in in vitro models of periodontal tissues. Acta Odontologica Scandinavica. ISSN 0001-6357. 85, p. 125–133. doi: 10.2340/aos.v85.45585. Full text in Research Archive
• Agger, Anne Eriksson; Hlinkova, Jana; Reseland, Janne Elin & Samara, Athina (2026). 3D models for oral inflammation using gingival fibroblasts, lipopolysaccharides and hypoxia | Scientific Reports. Scientific Reports. doi: 10.1038/s41598-026-47648-7. Full text in Research Archive Show summary

  Three-dimensional (3D) in vitro models that more faithfully recapitulate human tissue architecture are essential to advance mechanistic insight into inflammatory diseases. We developed and characterized a 3D human gingival fibroblast spheroid-system to dissect the combined effects of hypoxia and inflammation, two central features of host–pathogen interactions in periodontal disease and other chronic inflammatory conditions. Using controlled oxygen environments and stimulation with E. coli lipopolysaccharide (LPS) and IL-1β, we show that hypoxia alone markedly alters spheroid morphology, producing smaller aggregates with thinner rims, while the combination of hypoxia and inflammation yields the most prominent structural disruption. Cross-section analyses reveal condition-dependent remodeling of extracellular matrix and cytoskeletal organization, with coordinated reductions in fibronectin, collagen I/III, integrin β1, and filamentous actin. Gene expression profiling confirms suppression of extracellular matrix (ECM)-related and adhesion genes under hypoxia and combined stress, whereas secretome analysis demonstrates robust upregulation of pro-inflammatory cytokines and chemokines (IL-6, IL-8, MCP-1, TNFα) and angiogenic VEGFα. Despite these marked structural and immunological shifts, cell viability remained largely preserved. This 3D system captures key features of fibroblast responses to inflammatory and hypoxic cues, providing a human-relevant platform for studies of tissue remodeling, cytokine signaling, and microenvironmental stress relevant to host–pathogen–driven disease.

• Hlinkova, Jana; Dziemidowicz, Karolina; Ullrich, Mathilde M.; Agger, Anne Eriksson; Lian, Aina-Mari & Reseland, Janne Elin [Show all 7 contributors for this article] (2025). Neural growth patterns: how random and aligned fibers guide 3D cell organization and pseudospheroid formation. Frontiers in Bioengineering and Biotechnology. 13. doi: 10.3389/fbioe.2025.1659965. Full text in Research Archive Show summary

  Background and purpose Electrospun biomaterials replicate the structural complexity of the extracellular matrix (ECM), providing mechanical support and promoting neural cell survival and organization. Fiber orientation is a key determinant of neural cell behavior, influencing adhesion, migration, and differentiation. This study investigates how high seeding density combined with fiber directionality shapes SH-SY5Y culture morphology, gene expression, and early network formation; all critical factors for the design of next-generation scaffolds for neural tissue engineering. Methods Polycaprolactone (PCL) scaffolds with either random or aligned fiber orientation were fabricated via monoaxial electrospinning. Human SH-SY5Y neuroblastoma cells were seeded at high density and cultured for 7 days, and cell viability was assessed by lactate dehydrogenase (LDH) activity. Neural, ECM, and differentiation markers were analyzed using quantitative PCR, Luminex cytokine profiling, and confocal immunofluorescence. Results Hydrophobic PCL fibers supported cell adhesion, migration, and proliferation when cells were seeded in small clusters. After 7 days, cell coverage of the fiber-mat was significantly higher on random fibers compared to aligned ones (27.7% vs. 15.8%). Fiber orientation influenced both culture morphology and gene expression. Pseudospheroids formed on both substrates, that differed in perimeter (348.5 µm on random vs. 450.5 µm on aligned fibers, p < 0.05), with no significant difference in thickness (38.4 ± 7.7 µm vs. 43.2 ± 5.5 µm). mRNA expression of connexin 43 and β3-tubulin increased significantly from day 1 to day 7 on random fibers. On aligned fibers, mRNA patterns resembled cells cultured on glass (control), with elevated connexin 31 and doublecortin over time. Immunofluorescence showed early enrichment of nestin on aligned fibers (day 1), and greater expression of β3-tubulin, acetylated tubulin, and connexin 31 on aligned substrates, whereas fibronectin 1 was more prominent on random fibers. Conclusion Fiber orientation significantly affected SH-SY5Y cell behaviour, including adhesion, formation of pseudospheroids, and differentiation marker expression under high-density conditions. Random and aligned fibers elicited distinct structural patterns and molecular responses, highlighting the importance of scaffold architecture in the rational design of neuroregenerative platforms. To our knowledge, this is the first study to describe scaffold-anchored neural pseudospheroids as a distinct model from conventional suspension spheroids.

• Lauretis, Angela de; Agger, Anne Eriksson; Pal, Antara; Pedersen, Jan Skov; Szostak, Szymon Mikolaj & Lund, Reidar [Show all 10 contributors for this article] (2025). Balancing sterilization and functional properties in Poloxamer 407 hydrogels: comparing heat and radiation techniques. Regenerative Biomaterials. 12. doi: 10.1093/rb/rbaf005. Full text in Research Archive Show summary

  Poloxamer 407, also known as Pluronic® F127, is gaining interest in the cosmetic, biomedical, and pharmaceutical fields for its biocompatibility, safety, and thermosensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the hydrogel's functional properties. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy), and electron beam (e-beam) irradiation (15 kGy and 25 kGy) on a 30%w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared (FTIR) spectroscopy, Gel Permeation Chromatography (GPC), Small-angle X-ray scattering (SAXS), rheology, swelling, degradation by-products, and lactate dehydrogenase (LDH) release of the sterilised hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilisation alters the hydrogel’s gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel's elasticity, gelling, and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15 – 25 kGy range appears to be the most suitable method for sterilizing a 30%w/v Poloxamer 407 hydrogel.

• Munir, Arooj; Agger, Anne Eriksson; Samara, Athina; Reseland, Janne Elin & Solberg, Lene Bergendal (2025). Enhancing human osteoblast to osteocyte-like cell differentiation using 25-hydroxyvitamin D3 and all-trans retinoic acid combination. European Cells and Materials. p. 145–157. doi: 10.22203/eCM.v051a09. Full text in Research Archive Show summary

  Background: The individual effects of the 25-hydroxyvitamin D3 (25(OH)D3) and all-trans retinoic acid (ATRA) on osteogenesis have been studied in two-dimensional (2D) in vitro models, but the combined effect of these vitamins remains largely unexplored. Therefore, to address this knowledge gap we evaluated the effect of different concentrations of 25(OH)D3 and ATRA, individually and in combination, on differentiation of primary human osteoblasts (hOBs) over a 21-day period. Methods: The growth of hOBs, alkaline phosphatase (ALP) activity (cell bound and secreted), and the expression of bone-related markers were comprehensively evaluated at both gene expression level using real-time polymerase chain reaction (RT-PCR) and the proteins secretion through multiplex immunoassays. Results: Both 25(OH)D3 and ATRA enhanced hOBs differentiation. However, the combination of 10−6 M 25(OH)D3 and 10−5 M ATRA demonstrated the most pronounced effect, characterized by reduction in cell growth and enhancement in differentiation. This was further validated by elevated relative expression of osteoblast and osteocyte markers at both mRNA level (collagen type I alpha 1 (COL1A1), podoplanin (E11), and dentin matrix acidic phosphoprotein 1 (DMP1), and at protein level (osteopontin (OPN), osteocalcin (OCN), sclerostin (SOST), and fibroblast growth factor 23 (FGF23)). Additionally, 25(OH)D3 and ATRA were found to regulate the expression of key receptors involved in osteoblasts differentiation, including retinoic acid receptor alpha (RARα), retinoid X receptor beta (RXRβ), and vitamin D receptor (VDR). Conclusions: This study demonstrates that a combination of 10−6 M 25(OH)D3 and 10−5 M ATRA effectively enhanced the differentiation of hOBs to osteocyte-like cells in vitro.

• Agger, Anne Eriksson; Samara, Athina; Geng, Tianxiang; Olstad, Ole Kristoffer & Reseland, Janne Elin (2024). Mimicking and in vitro validating chronic inflammation in human gingival fibroblasts. Archives of Oral Biology. ISSN 0003-9969. 169, p. 1–11. doi: 10.1016/j.archoralbio.2024.106113. Full text in Research Archive Show summary

  Objective The aim of this study was to identify and validate in vitro conditions that may mimic the translational, cytokine and chemokine profiles observed in human inflamed gingiva in vivo. Design Primary human gingiva fibroblast cells (HFIB-G) were cultured under serum starvation conditions (0 – 10 %), supplemented with increasing lipopolysaccharide (LPS) concentrations (0.1, 1, or 10 µg/ml) from two bacterial strains E. coli and P. gingivalis and 0.1, 1, or 10 ng/ml recombinant interleukin 1β (IL-1β), alone or in combinations. The levels of cytokines/chemokines were measured in the cell culture medium by Luminex, and gene expression was quantified by Affymetrix microarrays at 24, 48 and 72 h. Results Inflammation markers were not elevated after stimulation with P. gingivalis LPS, while E. coli LPS and IL-1β individually increased the secretion of interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to the cell culture medium. IL-1β administration also increased the secretion of several factors, including tumor necrosis factor (TNFα). However, the combination of 1 µg/ml E. coli LPS, 1 ng/ml IL-1β and serum starvation led to increased secretion of IL-6, TNFα, in addition to other factors found in inflamed tissue. Gene expression analyses revealed that this combination not only enhanced the expression interleukins/chemokines genes but also T helper cell signaling and matrix metalloproteinases. Conclusion Serum reduction in cell culture medium together with the administration of E. coli LPS and IL-1β resulted in gene expression and secreted cytokine/chemokine profiles similar to that found in vivo during chronic inflammation.

• Vogelaar, Thomas Daniel; Agger, Anne Eriksson; Reseland, Janne Elin; Linke, Dirk; Jenssen, Håvard & Lund, Reidar (2024). Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers. Biomacromolecules. ISSN 1525-7797. 25(7), p. 4267–4280. doi: 10.1021/acs.biomac.4c00337. Full text in Research Archive Show summary

  To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

• Hussain, Badra; Khan, Sadia Nazir; Agger, Anne Eriksson; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter & Bueno, Jaime [Show all 7 contributors for this article] (2023). A Comparative Investigation of Chemical Decontamination Methods for In-Situ Cleaning of Dental Implant Surfaces. Journal of Functional Biomaterials. 14(8). doi: 10.3390/jfb14080394. Full text in Research Archive Show summary

  Surface chemistry evaluation is crucial in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone®Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilised for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel®. Among the tested chemical decontamination candidates, NuBone®Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone®Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomised clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in implant dentistry

• Agger, Anne Eriksson; Reseland, Janne Elin; Hjelkrem, Erik; Lian, Aina-Mari; Hals, Else Kristine Breivik & Zandi, Homan [Show all 7 contributors for this article] (2023). Are comorbidities associated with the cytokine/chemokine profile of persistent apical periodontitis? Clinical Oral Investigations. ISSN 1432-6981. 27, p. 5203–5215. doi: 10.1007/s00784-023-05139-3. Full text in Research Archive
• Yang, Yang; Geng, Tianxiang; Samara, Athina; Olstad, Ole Kristoffer; He, Jianying & Agger, Anne Eriksson [Show all 11 contributors for this article] (2023). Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D. Journal of Periodontal Research. ISSN 0022-3484. 58(2), p. 336–349. doi: 10.1111/jre.13094. Full text in Research Archive Show summary

  Abstract Background Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. Objectives To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. Materials and Methods Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. Results Approximately 1000 genes were differentially expressed between control and irisin-treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin-exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim-like structure on the outer region of the hPDL spheroids, ECM-related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. Conclusions Irisin altered the morphology in primary hPDL cell-derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

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• Agger, Anne Eriksson (2026). 3D Models of Inflammation: The Future of Oral In Vitro Pathophysiology? Universitetet i Oslo. ISSN 9788283271096. Full text in Research Archive Show summary

  Establishing human-relevant in vitro models of oral inflammatory diseases is essential to assess cell mechanisms and potential therapies. Such models aim to replicate key aspects of the in vivo environment, including cell and matrix interactions, ECM composition and metabolic activity. However, accurately reproducing the multifactorial nature of oral inflammation is challenging. 2D cell culture systems are traditionally used, yet 3D models more closely mimic tissue cytoarchitecture, signaling, tissue remodeling, and functional responses. In this thesis, clinically derived samples were explored to ensure that model development was grounded in human pathology. A 2D inflammation protocol was established, and adapted for a 3D model, which was further optimized by incorporating hypoxic conditions to enhance physiological relevance while maintaining high reproducibility and scalability. The resulting 2D and 3D fibroblast-based models represent simplified native-tissue versions and reproduced key features of oral inflammation, including cytokine secretion, ECM degradation, and cytoskeletal alterations. These processes are central to the development of chronic inflammatory disease.

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