Most recent publications

• Süslü, Safiyye; Haugen, Håvard Jostein; Krüger, Tormod Bjartveit; Reseland, Janne Elin & Herlofson, Bente Brokstad (2026). Medication-related osteonecrosis of the jaw in cancer and osteoporosis patients: a retrospective seven-year single-center Norwegian cohort study of clinical profiles and documented soft tissue healing. Acta Odontologica Scandinavica. ISSN 0001-6357. 85, p. 713–724. doi: 10.2340/aos.v85.46983. Full text in Research Archive Show summary

  Objective: To compare systemic profiles, oral findings, and documented soft tissue healing between cancer and osteoporosis patients with medication-related osteonecrosis of the jaw (MRONJ). Material and methods: This retrospective single-center cohort included 105 cases treated in 2013–2019 (56 cancer; 49 osteoporosis). Healing at last follow-up was analyzed using adjusted logistic regression and Firth sensitivity analysis. Results: Of 102 cases with known final status, 68 had documented healing. Osteoporosis cases were older, predominantly female, and had longer antiresorptive exposure than cancer cases (76.7 ± 11.1 vs. 70.0 ± 8.5 years; 102.5 ± 77.8 vs. 34.6 ± 28.5 months; both p < 0.001). Stage II predominated and Stage 0 was uncommon (3/105, 2.9%). Previous tooth extraction at the MRONJ lesion site was more frequent in osteoporosis (95.9% vs. 71.4%; p < 0.001). Surgical treatment was associated with higher healing odds (adjusted odds ratio [OR]: 11.12, 95% confidence interval [CI]: 4.12 to 33.35; p < 0.001), whereas cancer indication was associated with lower odds (adjusted OR: 0.23, 95% CI: 0.07 to 0.68; p = 0.011). Conclusions: Systemic profiles differed; oral patterns were similar. Non-random treatment and missing healing dates limit interpretation. Previous tooth extraction was the most frequent antecedent event; its indication and timing were unverified.

• Black, Charles S.; Kumar, Milen; Reyes, Renato Miguel; Leach, J. Kent; Lee, Mark A. & Haugen, Håvard Jostein [Show all 9 contributors for this article] (2026). Mesenchymal stromal cells in polytrauma: from immune dysregulation to therapeutic potential. Frontiers in Bioengineering and Biotechnology. 14. doi: 10.3389/fbioe.2026.1892227. Full text in Research Archive Show summary

  Polytrauma, defined as life-threatening injuries to multiple organ systems with an Injury Severity Score greater than 16, presents significant challenges for fracture healing, with nonunion rates substantially higher than in isolated fractures. The systemic inflammatory response syndrome (SIRS) and subsequent immune dysregulation characteristic of polytrauma create a hostile microenvironment that impairs normal bone regeneration. Mesenchymal stromal cells (MSCs; also termed mesenchymal stem/stromal cells) play critical roles in fracture healing through immunomodulation, osteogenic differentiation, and promotion of angiogenesis. However, emerging evidence suggests that MSC-mediated processes may be compromised in polytrauma settings. Importantly, direct evidence for endogenous MSC dysfunction in human polytrauma remains limited: much of the current understanding is inferred from isolated-fracture models, in vitro inflammatory-stimulation studies, and animal polytrauma systems rather than from controlled human trauma data. This review examines the mechanisms by which polytrauma is associated with disruption of MSC function, including altered macrophage polarization, excessive neutrophil activation, reduced regulatory T cell populations, and complement-mediated MSC injury. We synthesize the current understanding of MSC immunomodulatory effects in normal fracture healing and contrast this with their dysfunction in polytrauma, where MSCs adopt pro-inflammatory phenotypes and demonstrate impaired homing. Clinical applications of MSC-based therapies are discussed, including bone marrow aspirate concentrates and tissue-engineered constructs, alongside their potential for systemic immunomodulation in trauma patients. Throughout, we distinguish endogenous MSC behavior in polytrauma from exogenous MSC-based therapies, and we separate various MSC-based therapies as biologically and translationally distinct concepts. Finally, we outline critical knowledge gaps and propose future research directions, including development of representative polytrauma models, optimization of MSC delivery methods, and exploration of MSC-derived extracellular vesicles as therapeutic alternatives to improve outcomes in polytraumatized patients.

• D'Antonio, Francesco; Flacco, Maria Elena; Manzoli, Lamberto; Samara, Athina & Khalil, Asma (2026). GLP-1 receptor agonist exposure in the periconceptional period and adverse obstetric outcomes: A systematic review and meta-analysis. Med. ISSN 2666-6359. p. 101267–101267. doi: 10.1016/j.medj.2026.101267. Full text in Research Archive Show summary

  Background This systematic review and meta-analysis assesses whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during pregnancy or the periconceptional period is associated with adverse maternal and perinatal outcomes. Methods Medline, Embase, and the Cochrane Library were searched for observational studies comparing pregnancies exposed and unexposed to GLP-1 RAs within 6 months before a positive pregnancy test. Outcomes included miscarriage, intrauterine death, congenital anomalies, preterm birth (PTB), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), small for gestational age (SGA), large for gestational age (LGA), and excess gestational weight gain. Random-effects meta-analyses and subgroup analyses by indication were performed. Findings Ten studies included 2,118,215 women, of whom 8,325 were exposed and 2,109,890 were unexposed. Pooled estimates did not show a clearly detectable increase in miscarriage or intrauterine death, congenital anomalies, preterm birth, HDP, gestational diabetes, abnormal fetal growth, or excess gestational weight gain. A lower pooled estimate for preeclampsia was observed (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.78–0.98; p = 0.02), but this was based on two datasets and should be interpreted cautiously. Subgroup analyses showed no clearly detectable differences by indication. The exposure-window sensitivity analysis, covering 90 days before conception through the end of the first trimester, used the same four studies as the primary congenital-malformation analysis and therefore was not independent. Conclusion Available observational evidence did not identify a clearly detectable increase in adverse maternal or perinatal outcomes following periconceptional exposure to GLP-1 RAs. However, these findings do not establish safety because of heterogeneity, residual confounding, and limited datasets.

• Süslü, Safiyye; Haugen, Håvard Jostein; Krüger, Tormod Bjartveit; Herlofson, Bente Brokstad; Reseland, Janne Elin & Eriksen, Erik Fink (2026). Oral findings and antiresorptive therapy exposure duration in postmenopausal women with osteoporosis: a cross-sectional cohort study. BMC Oral Health. doi: 10.1186/s12903-026-09735-z. Full text in Research Archive Show summary

  Background Oral findings are common among older adults, but it is unclear whether they vary with the duration of antiresorptive therapy (ART) exposure or relate to the severity of osteoporosis in postmenopausal women. Methods In this cross-sectional cohort ( n  = 129), postmenopausal women undergoing osteoporosis assessment/follow-up were stratified by ART exposure duration: no current ART control (G1, n  = 50), short ART (G2, 3–5 years; n  = 39), and long ART (G3, > 5 years; n  = 40). The prespecified primary oral endpoint was any mucosal finding ( oral_mucosal_any ), defined as ≥ 1 prespecified mucosal lesion category at oral examination. The oral_mucosal_any endpoint was analysed by component to distinguish traumatic from non-traumatic mucosal findings. Secondary oral endpoints included tooth and molar counts, periodontal findings, and the number of mucosal lesion categories. Group differences were analysed using age- and BMI-adjusted regression (G1 reference). Secondary analyses compared oral findings across fracture-burden strata and hip BMD/T-score categories and evaluated whether oral variables improved discrimination for hip osteoporosis (total hip T-score ≤ − 2.5) beyond age, BMI, and ART group. Results Mucosal findings were common and non-monotonic across ART groups (G1: 52.0%, G2: 30.8%, G3: 52.5%). Among the 59 participants with any mucosal finding, traumatic changes were present in 43 (72.9%); in a mutually exclusive classification, 38 (64.4%) had traumatic-only findings. In age- and BMI-adjusted models, short ART was associated with lower odds of oral_mucosal_any versus controls (OR 0.38, 95% CI 0.16–0.93; p  = 0.035), whereas long ART did not differ (OR 0.94, 95% CI 0.38–2.33; p  = 0.894). Tooth and molar counts, periodontal burden, and non-traumatic mucosal findings showed no robust graded pattern with ART duration. Oral findings were broadly similar across fracture-burden strata and hip BMD categories. Adding total teeth and oral_mucosal_any increased apparent Area Under the Curve (AUC) for hip osteoporosis from 0.795 to 0.820, but optimism-corrected AUC changed only from 0.736 to 0.741 (corrected ΔAUC = 0.005). Conclusions In this cross-sectional cohort, common oral findings did not show a robust graded duration–response pattern across ART exposure groups and were not consistently associated with fracture burden or hip BMD strata. The broad mucosal endpoint was largely driven by common traumatic findings and should be interpreted as a clinically pragmatic but biologically heterogeneous endpoint. Oral variables added negligible optimism-corrected discrimination beyond age, BMI, and ART group.

• Esposito, Alessio; Fortunato, Gabriele Maria; Stasi, Mauro Di; Fradinho, Ana C.; Pacetta, Guglielmo & Soriano, Maria Grazia [Show all 16 contributors for this article] (2026). A Biomimetic Eye In Vitro Model to Investigate the Blood-Retinal Barrier Pathophysiology. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.6c00764. Full text in Research Archive Show summary

  Abstract Existing in vivo models for retinal pathologies are costly, time-consuming, and subject to regulatory challenges, promoting interest in advanced in vitro models that replicate the blood-retinal barrier. Challenges related to vascularization and structural multiscale interactions hinder the development of in vitro models, which are useful to study nutrient and drug exchange between the retina and systemic circulation. To address these issues, we developed a blood-retinal barrier in vitro model for studying retinal pathophysiology. It features an electrospun scaffold (Bruch’s membrane) placed between a culture chamber (vitreous humor) and a bioinspired microfluidic network (choroidal vasculature). The network, modelled from indocyanine green angiography of the human retina, is laser-engraved into a 15 mm PDMS disc with channels 70–800 μm wide. PLGA and gelatin electrospun scaffold were investigated to mimic Bruch’s membrane. The scaffold is fixed to the microfluidic network, assembled into a culture chamber, and integrated within a bioreactor. A peristaltic pump ensures a consistent flow in the channels. Biological validation included ARPE-19 cells cultured on Transwell, PLGA, or gelatin membranes, HUVECs within membrane-coupled microchannels, and dual-layer constructs. Cells were examined separately and together, allowing evaluation of epithelial, endothelial, and construct responses. All configurations showed progressive increases in metabolic activity and limited LDH release over 28 days. Cell-seeded constructs reduced FITC–dextran transport relative to acellular controls, with stable values between days 21 and 28. Blank-corrected TEER likewise increased during ARPE-19 culture and plateaued by day 21. PLGA constructs showed the greatest electrical and solute-transport resistance, although acellular controls confirmed a substantial material contribution. Confocal microscopy demonstrated HUVEC attachment and F-actin organization along the microchannels, while ARPE-19 monolayers exhibited continuous junction-associated ZO-1 staining that remained stable between days 21 and 28. Overall, the platform supported long-term epithelial–endothelial culture and provided a stable, perfusable system for studying oBRB transport and cellular interactions.

• Saiz, Augustine Mark; Jamous, Reem; Stötzel, Sabine; Rahmati, Maryam; Holmboe, Leonard Volrath & Johnson, Soren [Show all 16 contributors for this article] (2026). Limited Added Effect of Proline‐Rich P6 Peptide to Cross‐Linked Hyaluronic Acid After Partial Lateral Meniscectomy in Sheep. Smart Medicine. ISSN 2751-1863. 5(4). doi: 10.1002/smmd.70048. Full text in Research Archive Show summary

  This study evaluates whether a proline‐rich P6 peptide provides added benefit to a cross‐linked hyaluronic acid (HA) hydrogel after partial lateral meniscectomy‐associated osteoarthritis‐like change in sheep. The corrected four‐group framework includes Intact no‐surgery/no‐injection reference knees ( n  = 7) and 16 surgically injured knees from eight sheep assigned to Mnx (meniscectomy only, n  = 4), Mnx + HA ( n  = 6), or Mnx + HA + P6 ( n  = 6). Mnx + HA and Mnx + HA + P6 knees received intra‐articular injections at Weeks 0, 1, 2, and 4. Osteochondral tissues were evaluated at Week 12 by microCT, H&E scoring, and histochemical/immunohistochemical image analysis. Endpoint‐specific animal‐ or knee‐level models were used, with sheep identity included as a random effect when estimable. HA‐based treatment was associated with favorable trabecular microCT patterns after meniscectomy. However, the primary Mnx + HA + P6 versus Mnx + HA contrast was not significant for percent trabecular bone volume/BV/TV (+1.52 percentage points; 95% CI −2.22 to 5.26; p  = 0.427). Histology and IHC/histochemical findings showed selected exploratory tissue‐pattern signals, including collagen‐associated matrix staining, but did not establish consistent peptide‐specific superiority. These findings support cross‐linked HA as an intra‐articular biomaterial platform while defining requirements for confirmatory HA‐peptide hydrogel studies.

• Haugen, Håvard J.; Gjesdal, Sindre Kim; Kalonda, Don B.; Perale, Giuseppe & Rossi, Filippo (2026). A critical translational review of smart, bioinspired and multifunctional regenerative biomaterials for oral implant-site repair. Discover Materials. doi: 10.1007/s43939-026-00926-7. Full text in Research Archive Show summary

  Abstract This critical translational narrative review evaluates smart, bioinspired and multifunctional biomaterials for oral implant-site repair. The review addresses a specific translational problem: regenerative materials must stabilise a defect, support vascularised bone and soft-tissue healing, interact appropriately with host immunity and microorganisms, and remain manufacturable, sterile, affordable and regulatorily tractable. PubMed/MEDLINE, Scopus and Web of Science were searched through 30 April 2026 using standardised database-specific update strings. The searches retrieved 765 records; 346 unique records remained after deduplication, and 106 records were retained after application of the eligibility filters and included in the final synthesis. Eligibility criteria, evidence appraisal and author-consensus procedures are reported explicitly. The evidence is organised into five functional classes: structural, bioactive, responsive/adaptive, multifunctional and patient-specific systems. A defect-based clinical algorithm then links containment, vascularity, mechanical demand, wound closure and patient risk to material selection. Established grafts and membranes remain the clinical reference for many indications, but they are not intrinsically smart. Growth-factor carriers, platelet products, hyaluronic acid, enamel matrix derivative, antimicrobial and osteoimmunomodulatory systems, biofunctionalised surfaces, cells, genes, three-dimensional/four-dimensional constructs and peptide-functionalised materials are assessed according to distinct mechanistic, animal, human and routine-use evidence. The most credible next-generation products are not those with the greatest number of components, but those that solve a defined failure mode while preserving manufacturing control and clinical usability. Translation therefore depends on reproducible production, sterility assurance, release and degradation specifications, shelf life, regulatory classification, cost, reimbursement and comparative benefit within realistic surgical workflows.

• Jamous, Reem; Nysæther, Ingvild; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Fredriksson, Malin Vestin & Ellingsen, Jan Eirik [Show all 7 contributors for this article] (2026). Multi-Scale Assessment of Scaffold-Guided Regeneration in Human Extraction Sockets Using an Ultra-Porous TiO₂ Biomaterial. Acta Biomaterialia. ISSN 1742-7061. doi: 10.1016/j.actbio.2026.08.041. Full text in Research Archive Show summary

  Ultra-porous TiO₂ scaffolds are architected non-degradable ceramic graft substitutes, but human evidence relating their structural integration to local tissue maturation remains limited. This exploratory study assessed scaffold-associated healing in a prospective clinical cohort registered at ClinicalTrials.gov (NCT06269497; 10 patients, 11 treated sites). Cone-beam computed tomography (CBCT)-based segmentation at baseline and follow-up was used to quantify changes in bone volume, radiographic low-density/non-mineralized volume, and radiographically detectable scaffold volume. Eleven scaffold-associated specimens were examined using non-decalcified histology, histomorphometry, and immunohistochemistry; nine were retrieved at approximately 6 months, one at 4 months, and one at 9 months. CBCT showed within-site increases in bone and total tissue volume and a reduction in radiographically detectable scaffold volume. Histology showed extensive pore colonization by osteoid-rich tissue, localized mineralization, and limited residual cartilage, consistent with ongoing but incomplete matrix maturation. Normalized RunX2 showed a positive exploratory association with absolute bone volume change, whereas associations with osteocalcin were uncertain and endpoint-dependent. CD206/CD68 and the vessel-to-osteoid ratio were more closely associated with low-density/non-mineralized volume outcomes than with bone-volume change. Osteoclast-associated variables were evaluable in only four sites and were interpreted descriptively. These findings are exploratory and do not establish causality or comparative efficacy, but they characterize tissue-scaffold interactions during human extraction-socket healing.

• Hlinková, Jana; Huo, Yiru; Sukul, Mousumi; Lewis, David J.; Reseland, Janne Elin & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2026). Dual-crosslinked chitosan nanofibres - Balancing mechanical enhancement with cytotoxic risk. Biomaterials Advances. ISSN 2772-9516. p. 215050–215050. doi: 10.1016/j.bioadv.2026.215050. Full text in Research Archive Show summary

  This study evaluated the effects of dual-crosslinking strategies on the mechanical performance and biocompati- bility of chitosan-norbornene (Chi-NB) nanofibres for tissue reconstruction. Chi-NB, bearing 28.6 ± 1.4 mol% alkene groups, was processed into nanofibres via solution blow spinning. Dual crosslinking was conducted by photo-initiated thiol-ene crosslinking with dithiothreitol (DTT), achieving >95% norbornene conversion with minimal thiol oxidation, followed by exposure to tannic acid (TA). Structural and chemical validation was per- formed using SEM, NMR, XPS, FT-IR, and tensile testing. In vitro, unmodified fibres supported robust cell viabil- ity, however, TA/DTT-modified fibres caused up to 15-fold higher LDH release at low seeding-densities, mirrored in indirect conditioned medium exposure, implicating cytotoxic leachates. Confocal imaging confirmed cell ad- hesion and cytoskeletal organisation whereas transcript analysis revealed altered expression of genes related to stress response, metabolism, growth, and differentiation. Overall, TA/DTT crosslinking improved nanofibre me- chanical properties but introduced bioactive residues, highlighting the need for post-processing and seeding den- sity optimisation. These findings support the translational potential of Chi-NB scaffolds in skin and neural tissue engineering, but future refinements are required for these applications.

• Samara, Athina & Khalil, Asma (2026). Moving beyond associations: The role of mechanistic evidence in prenatal paracetamol safety. Med. ISSN 2666-6359. 7(6), p. 101142–101142. doi: 10.1016/j.medj.2026.101142. Full text in Research Archive Show summary

  Prenatal paracetamol safety has been debated due to inconsistent observational findings and inherent confounding. Here we argue that epidemiology alone cannot resolve biological plausibility. Human-relevant mechanistic models, including organoid and microphysiological systems, can complement population studies by testing causal pathways, refining interpretation, and enabling integrated evidence triangulation to better inform clinical guidance. Med home. Opens in new tab

• Rubenis, Kristaps; Vecstaudza, Jana; Ma, Qianli; Zaldenieks, Markuss; Haugen, Håvard Jostein & Loca, Dagnija [Show all 8 contributors for this article] (2026). Fabrication of macroporous amorphous calcium phosphate ceramic scaffolds by pressure-driven sintering at sub-zero temperature using ice microspheres as space holders. Materials & design. ISSN 0264-1275. 267. doi: 10.1016/j.matdes.2026.116312. Full text in Research Archive Show summary

  Controlled porosity in pressure-assisted sintered ceramics can be introduced using space holders, which are subsequently removed by heat or dissolution. For some materials, such as the biomaterial amorphous calcium phosphate (ACP), which can be pressure-sintered at room temperature but is sensitive to heat and moisture, finding a suitable space holder is challenging. Here we report that under a uniaxial pressure of 1500 MPa, ACP can be densified to more than 94% of its true density at ∼ -50 to −40 °C, allowing the use of solid substances at sub-zero temperatures as space holders. ACP samples compacted at 1500 MPa at sub-zero temperature had slightly lower density, and their Vickers hardness, biaxial flexural, and splitting tensile strengths reached approximately 80% of those compacted at room temperature. Nevertheless, their mechanical properties were similar to those reported for conventionally sintered hydroxyapatite. Ice microspheres were successfully used as space holders. However, due to crack formation, the highest splitting tensile strengths were exhibited by scaffolds fabricated at 190 and 500 MPa, rather than at 1500 MPa. The feasibility of using ice particles for the fabrication of porous scaffolds was also demonstrated using an alternative method, freeze isostatic pressing, and was shown in other bioceramic systems.

• Lauretis, Angela De; Santacroce, Marco; Wang, Qiang; Ramirez, Manuel; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2026). Combined Chemical and Mechanical Debridement Enhances Salivary Protein Removal from Titanium while Maintaining Biological Properties. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.5c01973. Full text in Research Archive Show summary

  Effective decontamination of dental implants is essential for managing peri-implant diseases, yet its impact on the salivary pellicle and cell response remains unclear. As the pellicle mediates bacterial and host cell interactions, investigating how decontamination alters its composition is key to understanding the effects on biological outcomes. Accordingly, we examined how a Poloxamer 407 (P407) hydrogel, a P407 + hydrogen peroxide (H2O2) hydrogel, a titanium brush, and their combinations influence the adsorbed salivary proteins and cell adhesion on OsseoSpeed-like titanium surfaces. Surfaces with salivary proteins were treated with different decontamination methods and re-exposed to saliva. Protein quantity was measured using the BCA assay, while the proteomic composition and molecular functions of the adsorbed proteins were determined by liquid chromatography-mass spectrometry and gene ontology analysis. Human bone marrow mesenchymal stem cell (hBMMSC) adhesion was assessed on the surfaces, and cytotoxicity was evaluated using an LDH assay. Protein-coated and protein-free surfaces served as controls. Although protein levels were consistent across groups after either decontamination or recontamination, each treatment produced a different proteomic profile. Mechanical decontamination, alone or combined with chemicals, enhanced protein removal efficiency. Combined treatments yielded reduced protein diversity following recontamination and enriched adhesion-related proteins. None of the treatments compromised hBMMSC adhesion nor made the surface cytotoxic. Decontamination methods selectively modify the proteomic profile. Combined chemical and mechanical decontamination promotes the removal of salivary proteins and limits their readsorption while preserving cytocompatibility, supporting their relevance to peri-implant health.

• Lakshmi, A. Maha; Kumari, Kusum; Rao, P. Venkateswara; Madaboosi, Narayanan; Chitra, S. & Özcan, Mutlu [Show all 8 contributors for this article] (2026). Luminescent mesoporous bioactive glass nanoparticles: Samarium-doping for enhanced bone regeneration, antibacterial activity, and bioimaging. Biomaterials Advances. ISSN 2772-9516. 187. doi: 10.1016/j.bioadv.2026.214944. Full text in Research Archive Show summary

  Developing multifunctional bioactive materials capable of promoting bone regeneration while enabling real-time monitoring remains a significant challenge in tissue engineering. In this study, samarium (Sm3+)-doped mesoporous bioactive glass nanoparticles (Sm-MBGNs) were successfully synthesized via a sol-gel method assisted by a microemulsion process to enhance both biological functionality and imaging capability. The incorporation of Sm3+ ions into the silicate network was systematically investigated, revealing improved structural and textural properties, including high specific surface area and well-defined mesoporosity. In vitro bioactivity was evaluated through simulated body fluid (SBF) immersion, where hydroxyapatite formation was observed and confirmed using physicochemical and structural analyses. The evolution of the apatite layer was also monitored through photoluminescence emission, indicating the potential of Sm-MBGNs for fluorescence-based bioactivity tracking. Cytocompatibility assessed using MG-63 osteoblast-like cells via MTT assay, along with hemolysis studies, demonstrated good biocompatibility. The samples exhibited noticeable antibacterial activity against Escherichia coli and Staphylococcus aureus based on inhibition zone measurements. Overall, the results suggest that Sm-MBGNs possess promising bioactivity, antibacterial behavior, and luminescent properties, indicating their potential as multifunctional materials for bone regeneration and bioimaging applications, although further quantitative validation is required.

• Rubenis, Kristaps; He, Xin; Demir, Öznur; Fu, Zhaoyue; Sigurjónsson, Ólafur Eysteinn & Hildebrand, Torben [Show all 13 contributors for this article] (2026). Eggshell-derived amorphous calcium phosphate for upcycled bone repair: An In-Vivo study. Materials Today Communications. 53. doi: 10.1016/j.mtcomm.2026.115391. Full text in Research Archive Show summary

  Critical-sized bone defects require grafting materials that support early osteogenesis and predictable defect bridging. In this study, we evaluated eggshell-derived amorphous calcium phosphate (ACP) granules in a rat calvarial defect model and compared them with ACP obtained from commercial hydroxyapatite (HAp) and with cross-linked hyaluronic acid (HA) gel alone. Eggshell-derived and HAp-derived ACP were synthesized by the same dissolution–precipitation route, using formulations previously characterized in detail for composition, amorphous phase stability, and in vitro bioactivity. Bilateral 5 mm calvarial defects in rats were filled with HA gel (INT/HA), HA + HAp-derived ACP (Control ACP), or HA + eggshell-derived ACP (Eggshell ACP). Grafts were mixed immediately before implantation using a dual-syringe system. Bone regeneration at 2 and 4 weeks was assessed by micro-computed tomography and histology. Both ACP-containing groups enhanced bone volume fraction and reduced trabecular separation compared with HA alone, particularly in the central region of the defect. Eggshell ACP promoted more consistent defect bridging, with a continuous lamellar bone-like layer and more mature collagenous and mineralized tissue at the bone–graft interface. Within the limitations of a non-load-bearing small-animal model, these findings indicate that eggshell-derived ACP combined with HA supports early bone regeneration and exhibits higher osteogenic activity than HA alone and HAp-derived ACP, warranting further investigation as a bone graft candidate.

• Moghanian, Amirhossein; Haugen, Håvard Jostein; Marović, Danijela & Safaee, Sirus (2026). Role of strontium incorporation on the structural network of 45S5 bioactive glass: A molecular dynamics investigation. Materials Today Communications. 52. doi: 10.1016/j.mtcomm.2026.115131. Full text in Research Archive
• Procházková, Petra; Parobková, Viktória; Hildebrand, Torben; Nogueira, Liebert Parreiras; Vrlíková, Lucie & Buchtová, Marcela [Show all 8 contributors for this article] (2026). Contrast Agents and Sample Preparation Strategies for Soft Tissue Imaging in X-ray Computed Microtomography: Review and Experimental Validation in Mouse Tissues. Tomography of Materials and Structures (JTMS). 11. doi: 10.1016/j.tmater.2026.100086. Full text in Research Archive Show summary

  Micro-computed tomography (micro-CT) is an effective technique for non-destructive high-resolution imaging of mineralized tissues; however, imaging of soft tissues is challenging due to their inherently low X-ray attenuation and poor contrast. Therefore, their visualization in absorption micro-CT requires the use of contrast agents (CA) such as iodine-based solutions, osmium tetroxide, phosphotungstic acid, and other polyoxometalates. The aim of this review is to outline the individual steps of sample preparation before micro-CT measurement, such as fixation, dehydration, and contrast enhancement of soft tissues, and summarize the most commonly used CAs in ex vivo visualization. In addition to the literature overview, we conducted comparative staining experiments on mouse organs using several widely applied CAs, with the aim of illustrating practical outcomes and challenges. Based on both the data published and our test results, we recommend the most suitable CAs for different tissue types, with emphasis on minimizing tissue damage and deformation, and devote particular attention to applications in mouse embryos.

• 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.

• Reese, Jan-Ole; Lund, Ingrid Maria Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2026). A dual-loop chemostat to investigate multi-species biofilms on implant surfaces under adjustable flow conditions. Frontiers in Microbiology. 17. doi: 10.3389/fmicb.2026.1751315. Full text in Research Archive Show summary

  Natural biofilms are typically composed of a mix of different microbial species and are often exposed to strong shear forces resulting from liquid flow. Simple biofilm models that attempt to study biofilms are based on a single species and on static growth conditions. To overcome these limitations, we developed a modular dual-loop reactor that decouples bacterial cultivation from hydrodynamic exposure, enabling independent control of nutrient availability (and thus, cell density) and flow rate (and thus, shear stress). Importantly, the system allows for testing different surface materials in a systematic manner. To validate our setup, we used a community of six keystone members of oral biofilms in conjunction with titanium materials of defined roughness that mimic dental implant surfaces. We found that biofilm mass, robustness, and species distribution not only differ significantly between static and dynamic growth conditions, but also vary strongly with different flow velocities. The biofilms formed under flow could be separated into two fractions, one that washed away very easily, and a more robust, basal layer. At low shear forces, overall biofilm mass was the highest, but at the expense of biofilm robustness. At medium shear forces, the robust fraction of the biofilm had the highest relative content of extracellular matrix. At the highest flow rates, the biofilm mass was low, but late colonizers (represented by the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans ) had the lowest relative abundance. This is in accordance with the concept that high flow of saliva reduces the risk of oral disease. Future applications of our system will include the systematic testing of antimicrobial coatings or surface design effects under defined flow regimes, opening the path toward better medical implants.

• Haugen, Håvard J.; Javed, Ayesha; Anwar, Nilab; Amiry, Zahra; Par, Matej & Tarle, Zrinka [Show all 8 contributors for this article] (2026). Bioactive restorative materials in dentistry: state of the art and clinical translation. Dentistry Review. 6(2). doi: 10.1016/j.dentre.2026.100165. Full text in Research Archive Show summary

  Objective Bioactive restorative materials offer the potential to support remineralization and reduce caries; however, their clinical translation remains limited. This narrative review critically evaluates the current landscape of bioactive restoratives, focusing on material composition, in vitro performance, biocompatibility, and the extent of clinical validation. Methods A literature search was conducted using PubMed® and Google Scholar®, covering publications from 2000 to 2024. The search terms included 'bioactive restorative materials', 'bioactive glass', 'Cention N', and 'Activa BioACTIVE'. Out of 1245 records screened, 149 studies (in vitro, in vivo, and clinical) met the inclusion criteria. Only English-language peer-reviewed articles were included. Results Bioactive glass (BAG)-based fillers consistently show ion release, local pH elevation, apatite formation, and antibacterial effects in laboratory studies. However, clinical trials remain limited in number, short, and methodologically varied. Cention N demonstrates acceptable outcomes in cervical restorations, while Activa BioACTIVE presents inconsistent clinical results despite bioactive claims. Comparative data with conventional composites are scarce. Significance While in vitro data are promising, current clinical evidence shows no clear long-term superiority of bioactive restoratives.

• Ma, Qianli; Staudigel, Katrin Anja; Rubenis, Kristaps; Fu, Zhaoyue; Hildebrand, Torben & Zaldenieks, Markuss [Show all 12 contributors for this article] (2026). Sustainable Eggshell-Based Amorphous Calcium Phosphate Scaffolds and Membrane Protein Hydrogel for Regeneration in Rabbit Femoral and Calvarial Defects. ACS Applied Materials & Interfaces. ISSN 1944-8244. doi: 10.1021/acsami.5c25453. Full text in Research Archive Show summary

  Critical-sized bone defects require grafts with ideal spatial supporting. We upcycled eggshell waste sustainably into porous amorphous calcium phosphate (ACP) scaffolds and evaluated their early bone-regeneration performance alone and in combination with flexible and bioactive adjuncts in vivo. ACP scaffolds with ∼60% porosity were fabricated by pressure-densification, using ice microspheres as space holders. Before implantation, ACP scaffolds were vacuum-infiltrated with a hyaluronic acid (HA) hydrogel to minimize internal voids. Bilateral critical-size femoral and calvarial defects were created in New Zealand White rabbits and reconstructed with one of four treatments: (1) Sham, (2) ACP scaffold (ACP), (3) ACP infused with HA hydrogel containing a proline-rich peptide P2 (ACP + HA/P2), or (4) ACP infused with HA/P2 supplemented with soluble eggshell membrane proteins (prepared by our lab, ACP + HA/P2 + SEPs). After 6 weeks, micro-CT and histology were performed. All ACP-containing groups showed greater defect filling and mineralization than the Sham group. Micro-CT analysis demonstrated that ACP + HA/P2 + SEPs achieved the highest bone volume and trabecular number and the lowest trabecular separation. Histology confirmed more extensive mineralized collagenous deposition on ACP scaffolds and a more integrated bone–material fusion zone in this group. In femoral defects with graft displacement, ACP scaffolds induced cortical–scaffold bone bridging within the marrow, most evident with SEPs. Eggshell-derived ACP scaffolds, particularly when paired with SEP-enriched HA hydrogel, enhance early regeneration of critical-sized bone defects. Upcycling the inorganic and organic constituents of eggshell waste yields a complementary, single-origin biomaterials package for sustainable bone repair.

• Haugen, Håvard Jostein; Sanz, Javier; Perale, Giuseppe; Saiz, Augustine Mark; Romandini, Mario & Rahmati, Maryam (2026). Bone Grafts: Everything You Need to Know. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70087. Full text in Research Archive Show summary

  Bone substitute biomaterials have become a sine qua non in periodontology and implant dentistry; however, the ideal material choice remains controversial. In this review, we examine natural grafts (autograft, allograft, xenograft) and synthetic grafts (alloplasts, composites, CAD‐CAM personalised materials), comparing them across the triad of osteogenesis, osteoinduction, and osteoconduction. After a thorough presentation of current classification, properties, and mechanisms of action of the various bone grafts, we outline their clinical applications across different indications and discuss future directions in the field. Autografts provide living cells and influential inductive factors, but at the expense of donor‐site morbidity and rapid, unpredictable resorption. Processed allografts and xenografts provide reliable osteoconduction and volumetric stability with reduced inductive potential. Modern alloplasts (β‐TCP, hydroxyapatite, bioactive glass) achieve outcomes comparable to those of natural grafts in selected indications, particularly for space maintenance. Composite strategies, which blend small fractions of autogenous chips with slowly resorbing xenografts or alloplasts and are protected by membranes or meshes, enhance contour stability in sinus floor elevation as well as in lateral and vertical bone augmentation (i.e., guided bone regeneration). In periodontal regeneration of intra‐bony and furcation defects, non‐autogenous bone grafts are added to biologics (e.g., enamel matrix derivatives, platelet concentrates) when space maintenance is needed. Bone substitute materials represent the gold standard for socket preservation, while their adjunctive benefits in peri‐implantitis reconstructive surgery remain limited. CAD–CAM patient‐specific scaffolds and peptide‐modified matrices may enhance fit and handling, but they face challenges related to cost, manufacturing, and regulatory hurdles. The main barriers to translation include batch‐to‐batch variability, regulatory heterogeneity, and limited long‐term safety data. Bioactive glasses are also promising, as they simulate native mineral and do not exhibit unfavourable resorption characteristics, especially when strontium is added or when they are used in combination with platelet concentrates. They, however, remain costly and have long manufacturing times, requiring strict quality control. Cost‐effectiveness remains decisive: indeed, only grafts that offer procedural savings through faster healing and fewer reinterventions are likely to be widely adopted. The future of bone grafts lies in precision biomimetics that integrate intelligent drug delivery, personalised design, and rigorous quality control, promising to extend clinical outcomes beyond the traditional autograft paradigm.

• Sahoo, Rajashree; Sanket, A. Swaroop; Pattnaik, Ananya; Pany, Swarnaprabha; Pradhan, Sanghamitra & Pati, Sanghamitra [Show all 9 contributors for this article] (2026). Designing of Porous Scaffolds for Tissue Engineering and Regenerative Medicine. Journal of materials chemistry. B. ISSN 2050-750X. 14(9), p. 2733–2773. doi: 10.1039/d5tb02507a. Full text in Research Archive Show summary

  The porous structure of the scaffolds influences the biological and physicochemical activities in the tissue regeneration process. The porosity also allows better distribution of nutrients and diffusion of biological fluids thereby dispersing the seeding material uniformly. The tissue regeneration or healing process of the damaged tissues sometime slows down and, in some tissues, it is not possible to heal. The accumulation or functionalization of different biomolecules in porous scaffold enhances the biomimetic property. In this review, the importance of designing porous scaffold and their fabrication process by using various traditional, advanced and combinatorial techniques have been discussed. Furthermore, specific applications for tissue regenerative ability in damaged tissues like bone, cartilage, trachea, skin, nerve, retina, cardiac, pancreatic, breast, GI tract, hepatic, kidney and reproductive tissues have been discussed in detail.

• Troha, Lara; Šraj, Borut; Par, Matej; Simeon, Paris; Haugen, Håvard Jostein & Tarle, Zrinka [Show all 8 contributors for this article] (2026). Filler amount influences long-term mechanical stability of experimental dental composites. Dental Materials. ISSN 0109-5641. 42(6), p. 1020–1030. doi: 10.1016/j.dental.2026.02.012. Full text in Research Archive Show summary

  Objectives This study evaluated the influence of real-time vs. accelerated aging protocols on the mechanical properties of experimental dental composites with varying filler contents, focusing on flexural strength (FS), flexural modulus (FM), and microhardness (MH). Methods Five Bis-GMA/TEGDMA-based composites containing Ba-glass microfillers and silica nanofillers with total filler amounts (wt%) of 55, 60, 65, 70, and 75 were prepared. Rectangular specimens (n = 20, 16x2x2 mm) were subjected to three real-time aging durations: 24-hour, 4-month, and 12-month water storage, or two accelerated aging conditions: 4-month water storage followed by 10,000 thermal cycles, and 4-month water storage followed by 10,000 thermal cycles and 5-day ethanol immersion. FS and FM were determined using three-point bending, and MH by the Vickers test. Fracture surfaces were examined by scanning electron microscope and the fractographic quantification was performed using R-based image analysis. Data were analyzed using two-way ANOVA and Tukey’s post hoc test (α = 0.05). Results Filler content and aging significantly influenced all properties. FS was unaffected by filler content until thermal cycling caused its deterioration in highest filled composites, while FM and MH increased with filler content (p < 0.05). Ethanol exposure transiently increased FS but reduced FM and MH (p < 0.05). After 12 months, all groups showed moderate decrease in FM, FS, and MH, with higher filler content showing the highest values (p < 0.05). Significance Real-time aging for 12 months resulted in lower FS, FM, and MH values than any of the accelerated aging protocols tested, except for FS of higher filled materials exposed to thermal cycling.

• Xu, Chun; Chen, Yuan; Romandini, Mario; Haugen, Håvard Jostein & Ivanovski, Sašo (2026). Nanoparticles in Periodontology and Implant Dentistry: From Mechanisms to Clinical Applications. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70075. Full text in Research Archive Show summary

  ABSTRACT Recent advances in nanotechnology are reshaping the landscape of periodontology and implant dentistry, particularly through the application of nanoparticles (NPs). This narrative review provides a comprehensive overview of the mechanisms and translational potential of NPs in these fields. Following a presentation of their classification and discussion of their physicochemical properties, the key biological functions of NPs are summarized. These include antimicrobial activity, immunomodulation, promotion of tissue regeneration, sustained drug delivery, and imaging applications. Collectively, these properties hold promise to revolutionize the diagnosis, prevention, and treatment of periodontal and peri‐implant diseases, improve osseointegration, and enhance both soft‐ and hard‐tissue regeneration. Nonetheless, issues related to biodistribution, biocompatibility, and potential toxicity warrant careful evaluation. This review critically synthesizes current knowledge, highlights recent innovations, and identifies key challenges and future directions to maximize the clinical impact of NPs in periodontology and implant dentistry.

• Samara, Athina & Khalil, Asma (2026). Cardiovascular Changes in Pregnancy: Reference Ranges and Role of Maternal Characteristics. In Maulik, Dev (Eds.), Doppler ultrasound in obstetrics and gynecology. Springer Publishing Company. ISSN 9783540230885. p. 21–41. doi: 10.1007/978-3-032-10702-2_3. Full text in Research Archive Show summary

  Pregnancy induces profound cardiovascular adaptations that ensure adequate maternal perfusion and fetal development. These changes involve systemic, structural, and functional modifications, driven by hormonal, metabolic, and haemodynamic factors. Maternal blood volume expands with disproportionate plasma volume rise, causing physiologic anaemia, while increased cardiac output, stroke volume, and heart rate accommodate growing circulatory demands. Hormones such as progesterone, estrogen, and relaxin mediate vasodilation, reduce systemic vascular resistance, and remodel the vasculature. Additionally, the uteroplacental circulation undergoes extensive vascular remodelling, including spiral artery transformation, enabling low-resistance, high-capacitance blood flow essential for fetal growth. Longitudinally, adaptations evolve across trimesters, with early vasodilation and cardiac output rising in the first, peak blood volume and compliance in the second, and maximal cardiac output with potential vena cava compression in the third. The peri-partum period features dramatic shifts, including auto-transfusion during labour and rapid post-partum normalisation. Non-invasive assessments, such as echocardiography, Doppler ultrasound, impedance cardiography, and emerging wearable technologies, can enable monitoring of maternal haemodynamics and placental function. Clinical implications are also significant. Inadequate cardiovascular or uteroplacental adaptation may lead to complications such as pre-eclampsia, intrauterine growth restriction, or placental insufficiency. Standardised protocols for assessing arterial stiffness, cardiac output, venous haemodynamics, and volume homeostasis have been proposed by International Working Groups. Moreover, reference ranges and functional haemodynamic testing further aid risk stratification, whereas future integration of biomarkers, artificial intelligence, and digital health tools promises personalised patient monitoring for improved maternal-fetal outcomes.

• Reese, Jan-Ole; Lund, Ingrid M. Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2026). A dual-loop chemostat to investigate multi-species biofilms on different materials under adjustable flow conditions. Frontiers in Microbiology. 17. Full text in Research Archive Show summary

  Natural biofilms are typically composed of a mix of different microbial species and are often exposed to strong shear forces resulting from liquid flow. Simple biofilm models that attempt to study biofilms are based on a single species and on static growth conditions. To overcome these limitations, we developed a modular dual-loop reactor that decouples bacterial cultivation from hydrodynamic exposure, enabling independent control of nutrient availability (and thus, cell density) and flow rate (and thus, shear stress). Importantly, the system allows for testing different surface materials in a systematic manner. To validate our setup, we used a community of six keystone members of oral biofilms in conjunction with titanium materials of defined roughness that mimic dental implant surfaces. We found that biofilm mass, robustness, and species distribution not only differ significantly between static and dynamic growth conditions, but also vary strongly with different flow velocities. The biofilms formed under flow could be separated into two fractions, one that washed away very easily, and a more robust, basal layer. At low shear forces, overall biofilm mass was the highest, but at the expense of biofilm robustness. At medium shear forces, the robust fraction of the biofilm had the highest relative content of extracellular matrix. At the highest flow rates, the biofilm mass was low, but late colonisers (represented by the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) had the lowest relative abundance. This is in accordance with the concept that high flow of saliva reduces the risk of oral disease. Future applications of our system will include the systematic testing of antimicrobial coatings or surface design effects under defined flow regimes, opening the path towards better medical implants.

• Wang, Qiang; Haugen, Håvard Jostein; Linke, Dirk; Lyngstadaas, Ståle Petter & Ma, Qianli (2026). Residuals of Chemical Cleaning Agents Impair Peri-Implant Cell Viability: An in Vitro Study. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.5c01777. Full text in Research Archive Show summary

  Background: Chemical debridement agents are commonly used during the cleaning of implants for peri-implantitis treatment; however, how these agents affect lesion healing remains unclear. In addition, the dose- and time-dependent effects of these residuals on implant biocompatibility remain poorly understood. Materials and methods: We evaluated the effects of active compounds in commercial products-3% hydrogen peroxide (H2O2), 0.43% sodium hypochlorite (NaClO), and 0.12% chlorhexidine with 0.05% cetylpyridinium chloride (CHX-CPC) at graded dilutions on murine osteoblastic cells (MC3T3-E1), human gingival fibroblasts (HGFs), and human bone marrow mesenchymal stromal cells (hBMSCs). Cells were cultured for 24 h, then exposed to the agents for 2, 12, or 24 h. Cytotoxicity and viability were assessed using lactate dehydrogenase (LDH) release and CCK-8 assays, while cell morphology was examined by scanning electron microscopy (SEM). Apoptotic gene expression (BCL2, MCL1, BAX) was analyzed after 2 h using quantitative PCR. Results: At high concentrations, H2O2 and NaClO significantly reduced LDH activity in supernatant, likely due to oxidant-induced enzyme inactivation. All three agents inhibited cell viability in a dose- and time-dependent manner, accompanied by cell shrinkage and deformation. Among the tested cell types, hBMSCs displayed greater resistance to H2O2, maintaining proliferative viability at 0.15% (1:20 dilution). Gene expression analysis revealed that concentrated H2O2 and CHX-CPC downregulated BCL2 and MCL1 expression in MC3T3-E1 cells, with broader suppression of these genes observed in HGFs across all agents. In hBMSCs, high concentrations of the agents did not significantly reduce BCL2 and MCL1 levels. Conclusion: Residual chemical debridement agents, when inadequately removed, compromise the viability of cells in peri-implant tissues in a dose- and time-dependent manner. hBMSCs exhibited greater resistance to apoptosis than MC3T3-E1 cells and HGFs. Thorough removal of residual chemical cleaning agents after peri-implant debridement is therefore crucial to preserve the biocompatibility of the implant and the healing

• D'Antonio, Francesco; Flacco, Maria Elena; Valle, Lorenza Della; Prasad, Smriti; Manzoli, Lamberto & Samara, Athina [Show all 7 contributors for this article] (2026). Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. The Lancet Obstetrics, Gynaecology, & Women's Health. doi: 10.1016/s3050-5038(25)00211-0. Full text in Research Archive Show summary

  Background Concerns have emerged about the impact of paracetamol use in pregnancy on child neurodevelopment, particularly in relation to autism spectrum disorder. We aimed to synthesise available evidence to investigate associations between prenatal paracetamol exposure and autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and intellectual disability. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Library from inception to Sept 30, 2025, for cohort studies reporting adjusted estimates of the risk of autism spectrum disorder, ADHD, and intellectual disability. Eligible studies used validated questionnaires or medical records to define outcomes, reported maternal comorbidities and treatments, and compared pregnancies with and without paracetamol exposure, whereas unadjusted studies were excluded. Quality assessment of the included studies was conducted using the Quality In Prognosis Studies (QUIPS) tool. The primary outcomes were the associations between prenatal paracetamol exposure and the likelihood of autism spectrum disorder, ADHD, and intellectual disability. Analyses were restricted to sibling-comparison studies with adjusted estimates, and odds ratios (OR) were calculated. Random-effects meta-analyses used the generic inverse variance method. Subgroup analyses were performed when possible (trimester, duration of use, offspring sex, and follow-up length). This study was registered with PROSPERO, CRD420251156690. Findings 43 studies were included in the systematic review, and 17 studies in the meta-analysis. When considering sibling comparison studies, paracetamol exposure during pregnancy was not associated with the risk of autism spectrum disorder (OR 0·98, 95% CI 0·93–1·03; p=0·45), ADHD (0·95, 0·86–1·05; p=0·31), or intellectual disability (0·93, 0·69–1·24; p=0·63). There was also no association between paracetamol intake during pregnancy and autism spectrum disorder (OR 1·03, 95% CI 0·86–1·23; p=0·78), ADHD (0·97, 0·89–1·05; p=0·49), or intellectual disability (1·11, 0·92–1·34; p=0·28) when considering only studies at low risk of bias according to QUIPS. This absence of association persisted when considering all studies with adjusted estimates and those with more than 5 years of follow-up. Interpretation Current evidence does not indicate a clinically important increase in the likelihood of autism spectrum disorder, ADHD, or intellectual disability in children of pregnant individuals who use paracetamol as directed, supporting existing recommendations on its safety.

• Samara, Athina & Khalil, Asma (2026). Pregnancy as a stress test: Reframing the fourth trimester as a window of intervention and postpartum precision medicine. Med. ISSN 2666-6359. 7(1), p. 100969–100969. doi: 10.1016/j.medj.2025.100969. Full text in Research Archive Show summary

  Pregnancy triggers profound physiological changes, yet postpartum recovery remains under-recognized despite its predictive significance for lifelong health. The fourth trimester offers a critical window to detect cardiometabolic, immunological, and mental-health vulnerabilities. We propose a precision postpartum medicine framework integrating human-relevant models, longitudinal multi-omics, and AI-enabled risk stratification to transform postpartum care.

• Lauretis, Angela De; Wang, Qiang; Santacroce, Marco; Thiede, Bernd; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2025). A Comparative Study of the Impact of Chemical Debridement Products on the Proteomic Profile of the Salivary Pellicle and Cell Adhesion on OsseoSpeed Titanium Dental Implant Surfaces. ACS Applied Materials & Interfaces. ISSN 1944-8244. 17(39), p. 54592–54592. doi: 10.1021/acsami.5c14570. Full text in Research Archive
• Li, Yi; Huang, Junling; Zhang, Yan; He, Yide; Cai, Dongxuan & Xu, Min [Show all 9 contributors for this article] (2025). LL-37—biofunctionalized titanium improves soft tissue seal surrounding the dental implant from the perspective of optimizing a race to the surface. Regenerative Biomaterials. 12. doi: 10.1093/rb/rbaf117. Full text in Research Archive
• Wang, Yi; Jiang, Qixing; Vorlaufer, Dominik; Bismarck, Alexander; Blaker, Jonathan James & Gresil, Matthieu (2025). Application of vitrimer-based sizing agent onto carbon fibres through thiol-ene photo-polymerisation. Composites Part A: Applied Science and Manufacturing. ISSN 1359-835X. 202. doi: 10.1016/j.compositesa.2025.109495. Full text in Research Archive
• Hadji, Peyman; Aapro, Matty; Al-Dagri, Nasser; Alokail, Majed; Biver, Emmanuel & Body, Jean Jacques [Show all 32 contributors for this article] (2025). Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. Journal of Bone Oncology. ISSN 2212-1366. 53. doi: 10.1016/j.jbo.2025.100694. Full text in Research Archive
• Stiliyanov-Atanasov, Kristiyan & Basu, Probal (2025). Molecular Self-Reassembled Regenerated Fibres and Their Significance in Tissue Engineering Bio-Composites. Fibers. 13(11). doi: 10.3390/fib13110149. Full text in Research Archive
• Samara, Athina; Hanton, Thomas; Thakar, Ranee; Jauniaux, Eric & Khalil, Asma (2025). Impact of climate change and environmental adversities on maternal and fetal health: the role of clinical practices and providers in mitigating effects and prioritising women's health in the UK. Frontiers in Global Women's Health. 6. doi: 10.3389/fgwh.2025.1483938. Full text in Research Archive Show summary

  The climate crisis poses profound risks to women particularly during pregnancy. With rising global temperatures and increasing frequency of extreme weather events, there is an urgent need for health initiatives and guidelines tailored to the unique vulnerabilities of pregnant individuals. We conducted a review of English-language literature from 2000–2024 using PubMed, Scopus, and Web of Science, focusing on “climate change,” “pregnancy,” and “maternal health,” and included original studies, reviews. Relevant policy documents, including some published in 2025 were also included. We examine the multifaceted challenges posed by climate change, such as extreme weather events, water scarcity, malnutrition, and exposure to environmental pollutants like contaminated air and water, which directly and indirectly affect maternal and fetal health. The review explores the associations between these environmental stressors and adverse pregnancy outcomes, including preterm births, low birth weight, and developmental complications. These challenges are compounded in low-resource settings where healthcare infrastructure is limited, exacerbating inequities in maternal care. Furthermore, we focus on key areas for further investigation, including the long-term health effects of in-utero exposure to pollutants. The review addresses evidence-based strategies to reduce the environmental impact of healthcare through early interventions, innovation, and strengthened initiatives. It emphasises empowering healthcare professionals to educate others, raise awareness among policymakers, advocate for climate-conscious policies, and promote sustainable practices reducing the carbon footprint of the healthcare system, with a focus on the UK. In response to these pressing concerns, leading professional organizations, such as the Royal College of Obstetricians and Gynaecologists (RCOG) in the UK, and the American College of Obstetricians and Gynaecologists (ACOG) in the US, are prioritizing the intersection of climate change and women's health. Their initiatives, which aim to mitigate the climate-change impacts on pregnancies and fetal health by promoting research, raising awareness, and developing actionable strategies, are also highlighted. By amplifying awareness and global collaboration, the suggested strategies aim to protect maternal and fetal health in the face of an escalating climate crisis.

• Neset, Mikael Thomassen; Nilsen, Roy Miodini; Løvås, Kristian; Halsøy, Kathrine; Reikvam, Håkon & Stokland, Ann-Elin Meling [Show all 14 contributors for this article] (2025). Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease. Acta Ophthalmologica. ISSN 1755-375X. 104(1), p. e28–e38. doi: 10.1111/aos.17556. Full text in Research Archive Show summary

  Purpose: To examine ocular surface changes and inflammatory tear fluid biomarkers in patients with thyroid eye disease (TED). Methods: We included 106 Graves' disease (GD) patients (36 without TED, 32 with active and 38 with inactive TED) and 106 age- and sex-matched healthy subjects for ophthalmological evaluation, including ocular surface status and Meibomian gland function. Tear fluid was analysed for 40 inflammatory biomarkers by a Luminex multiplex bead assay. The parameters were compared across subgroups. Results: GD patients with TED had significantly higher median (min–max) Ocular Surface Disease Index (OSDI) score than GD patients without TED, with a median score of 31.4 (0–86.4) compared to 7.3 (0–45.8) (p < 0.01). Eleven of 50 patients with moderate-to-severe and sight-threatening TED had a meibum quality score above seven, compared to none of the 20 patients with mild TED (p = 0.027). Tear fluid levels of chemokine (C–C motif) ligand 2 (CCL2) were significantly (p = 0.003) higher in GD patients compared to healthy subjects. CD40 ligand (CD40L) and CCL2 were higher in GD patients with TED compared with GD patients without TED (p = 0.002 and 0.013, respectively). As a combined biomarker to distinguish between GD patients with and without TED, OSDI score together with tear fluid levels of CCL2 and CD40L produced an area under the receiver operating characteristic (ROC) curve of 0.80, with sensitivity of 0.69 at a fixed specificity of 0.80. Conclusions: Our findings demonstrate increased tear fluid levels of CD40L and CCL2 in patients with TED, indicating their potential as diagnostic biomarkers. Increased ocular discomfort in patients with TED could be related to impaired meibum quality.

• Raveendran, Dhanya; Dalloul, Feras; Mietner, J. Benedikt; Barba, Enguerrand; Chen, Shouzheng & Zaytseva-Zotova, Daria [Show all 12 contributors for this article] (2025). 3D Printable Hydrogel Based on TEMPO-Oxidized Cellulose Nanofibrils and Fmoc-FF for Enhanced Biological Performance and Cell Adhesion. ACS Applied Nano Materials. 8(38), p. 18571–18583. doi: 10.1021/acsanm.5c03356. Full text in Research Archive Show summary

  Herein, we report a 3D printable ink made of a peptide-polysaccharide hybrid hydrogel composed of fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) peptide and TEMPO-oxidized cellulose nanofibrils (ToCNF), synthesized using a pH-dependent sol–gel transition method. The ToCNF suspension is synthesized through the mechanical breakdown of a cellulose pulp using a microfluidizer, followed by its oxidation mediated with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). The properties of the hybrid inks are compared in the presence (ToCNF/Fmoc-FF-Ca2+) and absence (ToCNF/Fmoc-FF) of the divalent cation Ca2+, which acts as the cross-linker, at two optimized weight ratios (r) of ToCNF and Fmoc-FF (r = 4.5 and 6.5). The rheological measurements show that the yield strength of the ToCNF/Fmoc-FF-Ca2+ gel is almost double that of the hydrogel composite without Ca2+ ions, especially at the concentration (C) of 10 mM CaCl2. This finding is further verified by 3D gel printing, which produced good quality prints with the cation cross-linked hydrogel. The structural analysis by Field Emission Scanning Electron Microscopy shows that the calcium ions can cross-link the ToCNF and also enhance the self-assembly of Fmoc-FF, which leads to the formation of rigid compact nanofibers even at physiological pH. The electrostatic interaction of the positively charged Ca2+ ions onto the negatively charged surface carboxylate groups of ToCNF and Fmoc-FF is analyzed by zeta potential (ζ) measurements. Small-angle X-ray scattering measurements give deeper structural insights into the interaction of Fmoc-FF with ToCNF. Cell responses to the hydrogels are studied in human dermal fibroblasts (NHDFs) in a direct contact test using a live/dead assay and in extract test using Alamar Blue and lactate dehydrogenase assays. The results show that high loading of Fmoc-FF decreases cell viability, while additional cross-linking with calcium reduces this cytotoxic effect.

• Saiz, Augustine Mark; Rahmati, Maryam; Baldini, Tony Daniel; Bhat, Aneesh Satish; Johnson, Soren & Liu, Mengyao [Show all 15 contributors for this article] (2025). Mesenchymal stem cells delivered via a bioactive disordered peptide-hydrogel platform modulate early inflammation and enhance skeletal repair in a polytrauma model. Journal of Tissue Engineering. 16. doi: 10.1177/20417314251397106. Full text in Research Archive Show summary

  Over 30% of polytrauma patients with bone fractures suffer from impaired healing and nonunion due to persistent systemic inflammation. Existing biologic strategies for bone repair primarily focus on osteogenesis but are not designed to modulate systemic immune dysregulation, limiting their utility in the polytrauma setting. To overcome this, we developed a hyaluronic acid-based hydrogel (HA) incorporating osteogenic intrinsically disordered peptides (P2) and mesenchymal stem cells (MSCs) to promote bone regeneration and modulate inflammation simultaneously. MSCs entrapped in hydrogels containing P2 (HA + P2) exhibited increased cell viability, alkaline phosphatase activity, and calcium deposition under in vitro polytrauma conditions compared to MSCs in hydrogels alone (HA). We utilized a murine polytrauma model (4 mm femoral osteotomy + blunt chest trauma) in mice. We studied the inflammatory response and bone formation over 21 days in mice treated with (1) HA, (2) HA + P2, or (3) HA + P2 + MSCs. We observed that adding P2 enhanced bone mineralization at the fracture site, yet transplantation of MSCs with P2 further increased mineralization. Both HA + P2 and HA + P2 + MSCs groups attenuated the systemic inflammatory response to near healthy baseline values. The HA + P2 group significantly accelerated the first stages of fracture healing by upregulating genes encoding for collagen biosynthesis, modifying enzymes, and extracellular matrix (ECM)-receptor interaction. Mice treated with HA + P2 + MSCs exhibited transcriptional regulation resulting in the upregulation of key repair genes related to cell cycle control, E2F transcriptional regulation, and TP53-mediated DNA repair, alongside downregulation of inflammatory pathways (IL-2, IL-3, and IL-5 signaling) and improved fracture healing. This study demonstrated that the combination of intrinsically disordered peptides and mesenchymal stem cells in HA-based hydrogels enhances bone formation, modulates both local and systemic inflammation, and improves structural organization at the fracture site in polytrauma conditions.

• Nysæther, Ingvild; Haugen, Håvard Jostein; Khassawna, Thaqif El; Jamous, Reem; Afnan, Shoresh & Santacroce, Marco [Show all 10 contributors for this article] (2025). Clinical Performance of Ultra‐Porous TiO2 Scaffold as Bone Graft Substitute in Human Alveolar Ridge Preservation—A Feasibility Study. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.70074. Full text in Research Archive Show summary

  Objectives This study evaluates the safety and osteoconductive potential of a ceramic TiO2 scaffold in human alveolar bone, hypothesising that placement in human extraction sockets is safe, supports bone ingrowth and preserves ridge dimensions. Material and Methods Nine subjects requiring the extraction of ≥ 1 premolar or molar tooth were enrolled. Full-thickness mucoperiosteal flaps were elevated. Following tooth extraction, porous ceramic TiO2 scaffolds were adjusted chair-side, placed into the extraction socket and covered by a resorbable collagen membrane. After 6 months of healing, before dental implant placement, a biopsy was performed at the site where the scaffold had been placed. Histomorphometric and micro-CT analyses were made. CBCT images were made at baseline and at 6 months to assess alveolar ridge dimensional changes. Implants placed in regenerated bone were followed for 21 months. Results Scaffold customisation with chairside adjustment was straightforward. No serious adverse events were observed during the 6 months following scaffold implantation. One scaffold was removed due to an early exposure, while the remaining 9 scaffolds successfully integrated. Two sites presented with minor soft tissue dehiscences at 1–2 weeks, which healed spontaneously. Micro-CT and histology confirmed new bone formation. Soft tissue healing was favourable, with no adverse reactions. Dimensional analysis revealed minimal changes in alveolar ridge width and height, indicating effective preservation of volume. Conclusions This clinical study confirms that TiO2 scaffolds are a safe and effective option for promoting bone regrowth and preserving volume in human alveolar bone, thereby facilitating bone formation and maintaining ridge dimensions post-extraction.

• 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 &lt; 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.

• Saiz, Augustine Mark; Rahmati, Maryam; Johnson, Soren; Bhat, Aneesh Satish; Baldini, Tony Daniel & Øvrebø, Øystein [Show all 13 contributors for this article] (2025). Systemic versus local delivery of mesenchymal stem cells to improve the early stages of fracture healing in a polytrauma model. Journal of Biological Engineering. 19(1). doi: 10.1186/s13036-025-00554-4. Full text in Research Archive Show summary

  Fracture healing complications, including nonunion, are common in polytrauma patients partly due to systemic inflammatory dysregulation. Although mesenchymal stem cells (MSCs) have been widely explored for their regenerative properties, their therapeutic potential in polytrauma patients remains uncertain. Given the clinical interest in both systemic and localized stem cell therapies, understanding how delivery route influences MSCs biodistribution, inflammatory modulation, and therapeutic efficacy is critical for optimizing treatment strategies in polytrauma. Hence, we compared systemic versus local MSCs delivery in a polytrauma model. We evaluated inflammatory responses and bone formation in a C57BL/6J murine model across four groups: (1) isolated fracture, (2) polytrauma (femur fracture + chest trauma), (3) polytrauma + systemic MSC delivery, and (4) polytrauma + local MSC delivery in hyaluronic acid-based hydrogels at the fracture site. Polytrauma induced a prolonged inflammatory response characterized by elevated interleukin 1 alpha and beta (IL-1α & β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and monocyte chemoattractant protein-1 and − 5 (MCP-1 & MCP-5). Both delivery methods significantly reduced inflammation and proinflammatory cytokines, though local delivery yielded more consistent effects. IVIS imaging confirmed MSC retention at the fracture site in the local delivery group, while systemic administration of MSCs resulted in pulmonary entrapment. Although systemic MSCs failed to enhance fracture healing significantly, local MSC delivery promoted bone formation evidenced by CT and histological characterizations. These findings demonstrate that local MSC delivery in a hydrogel scaffold represents a superior strategy for improving fracture healing in polytrauma patients compared to systemic delivery.

• Øvrebø, Øystein; Lyngstadaas, Ståle Petter; Khassawna, Thaqif El; Jamous, Reem; Ma, Qianli & Muñoz, Fernando [Show all 13 contributors for this article] (2025). Multiomics Comparison of Proline‐Rich Peptide‐Enhanced Hyaluronic Acid Gels Versus Conventional Regenerative Materials: An Early Wound‐Healing Model. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70032. Full text in Research Archive Show summary

  Aims To compare the early wound‐healing responses to crosslinked hyaluronic acid enriched with two proline‐rich peptides (P2, P6) against unmodified hyaluronic acid and the enamel‐matrix derivative (EMD) in a porcine gingival‐detachment model. Methods In six pigs, defects around premolars were treated with HA, HA + P2, HA + P6 or EMD. After 6 days, the sites were harvested and evaluated using histology, immunohistochemistry, multiplex cytokine assay and untargeted proteomics of the gels, which were examined, informing an integrated multiomics approach analysis. Results Both peptide formulations improved the composite histological score compared to HA alone, and HA + P6 matched EMD in suppressing oedema, TNF‐α staining and CD80 + macrophages while increasing mannose‐receptor labelling. Proteomics revealed that P2 upregulated actin (Q6QAQ1) and histone H2A (F2Z5L5), consistent with active remodelling, whereas EMD reduced trypsin and trypsinogen, indicating a more stabilised wound milieu; HA + P6 showed an intermediate yet favourable profile. IL‐6 levels were lower in both peptide groups and EMD than in HA, and all gels proved noncytotoxic, with HA + P6 enhancing cell viability. Conclusion HA + P6 suppressed TNF‐α and trypsin signalling while boosting M2‐linked markers and proresolution proteins to the same extent as EMD, whereas plain HA did not. Thus, adding a short proline‐rich peptide confers EMD‐like early immunomodulation on a fully synthetic HA carrier. These observations, although limited to 6‐day soft tissue healing, warrant longer studies in true periodontal regeneration models.

• Lauretis, Angela de; Wang, Qiang; Santacroce, Marco; Thiede, Bernd; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2025). A Comparative Study of the Impact of Chemical Debridement Products on the Proteomic Profile of the Salivary Pellicle and Cell Adhesion on OsseoSpeed Titanium Dental Implant Surfaces. ACS Applied Materials & Interfaces. ISSN 1944-8244. 17, p. 54579–54592. doi: 10.1021/acsami.5c14570. Full text in Research Archive Show summary

  Background and objectives: Dental implants are commonly used for tooth replacement, with excellent success rates over 10 years. However, exposure to oral cavity bacteria makes them susceptible to biofilm accumulation, which can lead to peri-implant diseases. The salivary pellicle, a protein-rich layer formed on implant surfaces, mediates bacterial adhesion and cell attachment. Effective decontamination is essential for managing bacterial infections, yet no consensus exists on the best chemical agent. Understanding how chemical agents affect the pellicle proteomic profile may guide the selection of optimal treatments. Methods: We investigate the impact of chemical decontamination agents on the salivary pellicle on OsseoSpeed-like titanium dental implant surfaces using a BCA assay and proteomics, and on cell adhesion using human gingival fibroblasts (HGF) and human bone marrow mesenchymal stem cells (hBMSC). We compare the effects of hydrogen peroxide (H2O2), Poloxamer 407 (P407), P407 + H2O2 and sodium hypochlorite + amino acids (NaOCl + AA) using the salivary pellicle and a clean titanium surface as controls. By quantifying and identifying proteins on titanium surfaces after decontamination, this study reveals how chemical agents affect the salivary pellicle. Results: All products reduced the total protein on the surfaces, with the P407 + H2O2 hydrogel demonstrating lower protein variety and superior effectiveness in preventing surface recontamination. Not all proteins were removed during decontamination procedures, and unique proteins were detected in each experimental condition, suggesting protein readsorption depends on surface chemistry. P407 + H2O2 shows the highest enrichment in integrin- and cadherin-binding proteins upon recontamination. P407 and P407 + H2O2 promoted HGFs and hBMSCs attachment. Conversely, NaOCl + AA and H2O2 showed lower HGFs and hBMSCs counts. Conclusion: The P407 + H2O2 hydrogel had the strongest decontamination effect and limited surface recontamination. Each chemical agent produced a distinct proteomic profile. P407 and P407 + H2O2 promoted initial cell adhesion.

• Remartinez, Enrique Oreja; Zaytseva-Zotova, Daria; Rogala, Agnes; Bautista, Alejandro Barrantes; Messersmith, Phillip B. & Tiainen, Hanna (2025). Multifunctional tannic acid and polyamino acid layer-by-layer coatings for tailored implant surfaces. ACS Biomaterials Science and Engineering. 11(9), p. 5376–5388. doi: 10.1021/acsbiomaterials.5c00832. Full text in Research Archive
• Samara, Athina; Coutinho, Conrado Milani; Heath, Paul T. & Khalil, Asma (2025). Is maternal SARS-CoV-2 infection in the first trimester associated with congenital heart defects? Frontiers in Pediatrics. doi: 10.3389/fped.2025.1643423. Full text in Research Archive Show summary

  Emerging evidence suggests a potential link between maternal SARS-CoV-2 infection during early pregnancy and the development of congenital heart defects (CHD) in offspring. Although vertical transmission of SARS-CoV-2 is rare, the virus has been associated with placental complications and increased maternal morbidity. Recent studies from China report increased rates of CHD and anomalies such as situs inversus when infection occurs during gestational weeks 4–6, a critical window for cardiac development. Additional reports from different parts of the world also highlight post-pandemic increases in specific cardiac anomalies, including ventricular septal defects (VSDs). Multiple mechanisms may underlie these associations. SARS-CoV-2 can induce placental inflammation, compromise the cytotrophoblast barrier, and impair nutrient and gas exchange, potentially leading to fetal hypoxia and disrupted morphogenic signalling. Furthermore, maternal inflammation and elevated cytokines, along with viral effects on ACE2-expressing fetal cardiac progenitors, could further affect proliferation, differentiation, and apoptosis during cardiac development. Co-infections, hormone disruption, and maternal stress could also contribute. There is an urgent need for longitudinal studies with comprehensive maternal-fetal data, including infection timing, vaccine status, and biological sampling. These will be essential to delineate the multifactorial impacts of maternal infection on fetal cardiac development and long-term outcomes. Special focus should be placed on infections during early pregnancy (weeks 4–7), the period of cardiac septation and left-right asymmetry establishment, to determine causality and inform prevention strategies.

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• Saghir, Saloua; Samara, Athina; Hlinkova, Jana & Schiavone, Giuseppe (2026). REUSABLE PLATE-WELL INSERTS WITH HYDROGEL SCAFFOLDS FOR 3D CELL CULTURE. Full text in Research Archive
• Samara, Athina & Khalil, Asma (2026). Paracetamol in Pregnancy: Reassurance Amidst Uncertainty. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 133(5), p. 877–883. doi: 10.1111/1471-0528.70129. Full text in Research Archive
• Hildebrand, Torben; Ma, Qianli; Loca, Dagnija; Rubenis, Kristaps; Locs, Janis & Nogueira, Liebert Parreiras [Show all 7 contributors for this article] (2025). Contrast-enhanced Micro-CT for improved visualization of ACP-Engineered Osteoblastic Spheroids. Full text in Research Archive Show summary

  Introduction: Bone tissue engineering (TE) aims to develop biomaterials that replicate the specific mechanical strength essential for the functional characteristics of the bone. Osteoblastic spheroids provide a three-dimensional (3D) culture model that better mimics in vivo conditions than traditional two-dimensional (2D) cultures. Amorphous calcium phosphate (ACP), derived from eggshell waste, has shown enhanced osteogenic potential, making it a promising biomaterial for TE applications. However, due to limited penetration depth and structural distortion, conventional imaging techniques such as confocal microscopy and histology pose challenges in visualizing 3D constructs. This study evaluates contrast-enhanced micro-computed tomography (micro-CT) as a non-invasive alternative for 3D morphological analysis of ACP-engineered osteoblastic spheroids. Methods: Osteoblastic spheroids were cultivated using flat-bottom, U-bottom, and rotary flask techniques. Spheroids were supplemented with ACP derived from eggshell waste and synthesized ‘control’ ACP to assess its effects on osteogenic differentiation. Contrast-enhanced micro-CT imaging was performed using phosphotungstic acid (PTA) and iodine-based contrast agents. Scans were performed with a laboratory nano-CT (SkyScan 2211 Multiscale x-ray Nano-CT System, Bruker) and at the Synchrotron Radiation for Medical Physics (SYRMEP) beamline in the synchrotron laboratory ELETTRA (Trieste, Italy). Imaging results were compared with confocal laser scanning microscopy, scanning electron microscopy, and classical histology. Results: The cultivation method significantly influenced spheroid morphology, with rotary flask cultivation producing the most structurally uniform spheroids. ACP incorporation enhanced osteogenic activity and spheroid integrity and altered the spheroids’ morphology in volume and roundness. Contrast-enhanced micro-CT provided superior overall visualization of the spheroid and of internal architecture, allowing detailed analysis of cell and ACP distribution and matrix deposition. Unlike traditional imaging techniques, micro-CT enabled virtual histology without sectioning artifacts or depth limitations. Discussion: This study underscores the need for advanced imaging modalities to evaluate engineered tissues effectively. Contrast-enhanced micro-CT offers a non-invasive, high-resolution approach for visualizing cellular interactions within biomaterials, addressing key limitations of conventional imaging techniques. The findings support the integration of ACP into bone TE strategies and demonstrate the potential of micro-CT for enhancing the assessment of biofabricated constructs, particularly for large cell models including a mineralized portion.

• Hildebrand, Torben (2025). Optimising Contrast-Enhanced Micro-CT Techniques for Comprehensive Visualisation of Dental Structures. Universitetet i Oslo. ISSN 9788283271003. Full text in Research Archive Show summary

  For å få bedre innsikt i samspillet mellom bløte og harde vev, og sykdommene som rammer dem, trenger vi gode avbildningsteknikker innen odontologisk og regenerativ forskning. Vanlig mikro-CT viser mineraliserte strukturer som emalje og dentin svært godt, men bløtvev fremstår kornete fordi røntgenkontrasten er lav. Med kontrastforsterket mikro-CT kan vi «farge» bløtvevet kjemisk og dermed hente frem detaljer i tre dimensjoner. Torben Hildebrand har i doktorgradsavhandlingen sin undersøkt hvordan vi kan presse laboratoriebaserte mikro-CT-systemer til å nærme seg bildekvaliteten fra veldig avanserte synkrotronbaserte metoder. Han har testet ulike kontrastmidler, blant annet jod og fosfortungstensyre, og sett på hvordan skånsom demineralisering kan gjøre grensen mellom ulike vevstyper tydeligere. Testmetodene er prøvd ut på mennesketenner, musekjever og kunstige vevskonstruksjoner. Resultatene viser at de forbedrede mikro-CT-oppsettene gir høyoppløselige bilder av både bløte og harde vev, slik at vi kan utføre «virtuell histologi» uten å snitte i prøvene. Metodene fungerer godt sammenlignet med tradisjonell histologi og synkrotronbilder. Denne tilnærmingen gjør avansert 3D-avbildning mer tilgjengelig og åpner nye muligheter innen odontologisk og regenerativ forskning.

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