Håvard Jostein Haugen

• 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.

• 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.

• 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.

• Moghanian, Amirhossein; Kizilkurtlu, Ahmet Akif; Pazhouheshgar, Arang; Esfahani, Mohammad Nasr; Akpek, Ali & Marovic, Danijela [Show all 8 contributors for this article] (2026). Bioactive glasses as reactive biomaterials: Dissolution-driven structure–function relationships and predictive modelling. Acta Biomaterialia. ISSN 1742-7061. doi: 10.1016/j.actbio.2026.08.005. Full text in Research Archive Show summary

  Bioactive glasses (BGs) are reactive biomaterials whose biological effects arise from dissolution: ion exchange, pH evolution, surface-layer formation and calcium phosphate precipitation. Their performance is therefore shaped not by nominal composition alone, but by glass structure, processing, crystallinity, surface area, form factor, medium and test protocol. This critical narrative review reframes BG bioactivity as a time-resolved structure–dissolution–function problem and examines which predictive claims are currently justified. We distinguish direct BG evidence from mechanistically relevant non-BG glass studies and modelling examples from adjacent fields. We discuss how network connectivity, Qⁿ speciation, phosphate and borate structure, modifier identity, structural heterogeneity and accessible surface area govern ion release, pH, surface-layer evolution and mineralisation. Silicate, borate/borosilicate, phosphate-based and sol–gel/mesoporous systems are compared as distinct dissolution programmes rather than fixed bioactivity labels. Atomistic simulations are considered useful sources of structural descriptors when checked against experimental dissolution and biological data. Across these systems, ion-release profiles, pH and supersaturation trajectories, mineralisation kinetics, cytocompatibility windows, antimicrobial or angiogenic cues and mechanical retention can only be interpreted when exposure protocols are reported. Current modelling evidence is strongest for physicochemical outputs, particularly dissolution and ion release under defined conditions. Predicting pH, mineralisation, and cell response requires measured exposure variables, biological metadata, and external validation; in vivo performance remains indirect without paired datasets. We conclude that progress depends less on more complex models than on better-reported experiments, clear uncertainty and cautious claim boundaries.

• 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.

• 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
• 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.

• Moghanian, Amirhossein; Haugen, Håvard J. & Marović, Danijela (2026). From atomic scale to biological performance: the role of magnesium in solubility of the network and bioactivity of 45S5 Bioglass®. Journal of Non-Crystalline Solids. ISSN 0022-3093. 680. doi: 10.1016/j.jnoncrysol.2026.124046. Full text in Research Archive Show summary

  Understanding the multiscale structural behavior of magnesium-doped 45S5 bioactive glasses (BGs) is essential for optimizing their performance in tissue engineering and bone regeneration. In this study, eight compositions (45-M0 to 45-M20) with 0-20 mol% MgO were investigated using a combined molecular dynamics (MD) simulation and experimental analysis. The MD results showed that network connectivity (NC) increased from 1.926 in 45-M0 to 1.953 in 45-M5, and then to 2.035 in 45-M20. The ion clustering (R-factor) analysis showed that the most homogeneous cation distribution occurs in the 45-M5 compound, which exhibits the lowest Ca–Ca and Mg–Mg aggregation. The experimental results also confirmed the MD predictions: ICP-AES analysis after 24 hours of immersion in SBF solution showed that 45-M5 had the most balanced ion release and pH change. FE-SEM images also confirmed the uniform and rapid formation of the hydroxyapatite layer in this compound. Taken together, the 45-M5 compound offers an optimal balance between network stability and bioactivity, and was introduced as an optimal MgO content for tissue engineering and bone regeneration applications, and can pave the way for the development of a new generation of tunable BGs.

• 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.

• 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

• 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
• 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.

• 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.

• Pizzetti, Fabio; Vanoli, Valeria; Magaletti, Roberta; Nogueira, Liebert Parreiras; Gelosa, Simone & Haugen, Håvard Jostein [Show all 10 contributors for this article] (2025). Multiple release of fertilizers and pesticides from biodegradable bicontinuous structures. Journal of Industrial and Engineering Chemistry. ISSN 1226-086X. doi: 10.1016/j.jiec.2025.02.053. Full text in Research Archive Show summary

  Bicontinuous bijel like structures have been of relevant importance in biomedical field in recent years thanks to their biocompatibility and ability to successfully load and release both hydrophilic and hydrophobic drugs. Their structure can also be tuned by changing the nanoparticles that stabilize the system constituted by organic and the aqueous phases in similar amount. These qualities can also promote their usage in many other fields. Agrochemical industry, for instance, is currently searching for some multiple fertilizer/pesticide release systems in order to increase the fertilizer efficiency when treating the soil on one side, since much of them are lost in the environment as contaminants. On the other the use of pesticides is, year by year, limited by very strict rules and so their smart delivery is pivotal to achieve agriculture goals without causing pollution. In this work, the single loading and release of a representative fertilizer (urea) and a representative pesticide (atrazine) through a bijel-based structure has been studied. In particular, their effect on the structure properties have been considered, as far as the release properties in a different media, simulating what is happening in crop production.

• 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.

• Giorgi, Zoe; Veneruso, Valeria; Petillo, Emilia; Vangosa, Francesco Briatico; Nogueira, Liebert Parreiras & Haugen, Håvard Jostein [Show all 9 contributors for this article] (2025). Exploring the Role of Aqueous Buffered Saline Solutions on the Macroscopic Properties of PEG/Carbomer/Agarose Hydrogels. Macromolecular Bioscience. ISSN 1616-5187. p. 2500073–2500073. doi: 10.1002/mabi.202500073. Full text in Research Archive Show summary

  Nowadays, during hydrogel formulation design, the focus is primarily on polymers and cross-linkers. It is crucial to ensure a high level of biocompatibility and degradability, along with appropriate physico-chemical properties. However, other ingredients can also influence hydrogel formation and performance. Therefore, this study examines the effect of different salt molarities in phosphate buffered saline (PBS) solutions, used as reaction solvents, on the properties of hydrogels mainly composed of polyethylene glycol, agarose, and carbomer. To conduct the study, two PBS solutions are prepared by varying the salt concentrations, and these mixtures are used as solvents in a bulk polycondensation reaction. Subsequently, the two hydrogel formulations obtained are characterized to analyze the effect of PBS concentration on the material properties. An increase in salt concentration reduced the swelling capacity and release ability of the hydrogel matrix, as well as decreased the porosity and interconnectivity of the material, contributing to non-homogeneity in the pore network. Consequently, these results highlight that the salinity and ionic strength of buffering solutions can affect various material properties, and therefore, careful consideration should be given during the preparation of these solutions.

• Abedi, Niloufar; Khoshouei, Aida Sadeghian; Kouhi, Monireh; Haugen, Håvard Jostein; Savabi, Omid & Nejatidanesh, Farahnaz (2025). Immunomodulation in Bone Tissue Engineering: Recent Advancements in Scaffold Design and Biological Modifications for Enhanced Regeneration. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.4c01613. Full text in Research Archive
• Wang, Qiang; Haugen, Håvard Jostein; Linke, Dirk; Lyngstadaas, Ståle Petter; Sigurjonsson, Olafur & Ma, Qianli (2025). Impact of different chemical debridement agents on early cellular responses to Titanium dental implants: a transcriptome-based In Vitro Study on Peri-implant tissue regeneration. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 253. doi: 10.1016/j.colsurfb.2025.114727. Full text in Research Archive Show summary

  Background Poor peri-implant health leads to biofilm accumulation, peri-implantitis, and bone loss. Chemical debridement may help maintain peri-implant health, but its effects on peri-implant cells remain unclear. Methods Five cleaning agents—hydrogen peroxide (H2O2), Poloxamer, H2O2 +Poloxamer, Perisolv, and Paroex—were applied on titanium (Ti) surfaces. Mouse pre-osteoblasts (MC3T3-E1), human gingival fibroblasts (HGF), and human bone marrow stromal cells (hBMSC) were cultured on agent-treated Ti surfaces for up to 120 minutes to assess morphology, cytotoxicity, adhesion, and proliferation. RNA sequencing was performed on hBMSC. Results Except for Poloxamer, all treatments inhibited cellular spreading. Paroex increased cytotoxicity and inhibited proliferation. Perisolv impaired hBMSC adhesion and variably affected proliferation. H2O2, alone or with Poloxamer, elevated cytotoxicity and inhibited adhesion in hBMSCs but not MC3T3-E1 or HGF. In contrast, Poloxamer-treated Ti surfaces enhanced adhesion and proliferation across all cell types. RNA sequencing revealed that oxidant-based treatments (H2O2, H2O2 +Poloxamer, Perisolv) suppressed key genes for proliferation (HMGA2, JAG1, NOTCH1, YAP1, TBX3), anti-apoptosis (MCL1, BCL2L2), and adhesion (ITGA2, ITGB3, SPP1), while inhibiting MAPK, PI3K-Akt, and pluripotency pathways. Conclusion Commercial agents like Perisolv and Paroex impair hBMSC function, with Paroex demonstrating significant cytotoxicity. H2O2 exhibits toxicity, particularly to hBMSCs. Poloxamer improves cell attachment and growth. Given these findings, careful selection of debridement agents is critical to balance cleaning efficacy and cytocompatibility. The adverse effects on hBMSCs necessitate prompt removal postapplication. Further research on biomaterials supporting tissue regeneration postdebridement is needed to restore peri-implant health.

• Capotorto, Elena; Chiudaroli, Licia; Montrasio, Edoardo; Nogueira, Liebert Parreiras; Pitton, Matteo & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2025). Toward improved auricle reconstruction: The role of FDM 3D printing with PCL and TPU materials. Biomaterials Advances. ISSN 2772-9516. 169. doi: 10.1016/j.bioadv.2025.214175. Full text in Research Archive Show summary

  Microtia, along with trauma, represents one of the main causes of external ear malformation. Different clinical techniques were developed for the reconstruction of the auricle, but they all have some drawbacks. This work is focused on the development of an innovative 3D porous scaffold, printed by Fused Deposition Modelling (FDM) and based on laser-scanned images of the healthy contralateral ear of the patient. The scaffold was printed using polycaprolactone (PCL) and thermoplastic polyether urethane (TPU) to mimic the components of the cartilage and adipose tissue. After the optimization of the printing parameters, the 3D surface obtained as an output of the laser scan was elaborated, sliced and used as input for printing the layered structure. Morphological analysis confirmed the shape fidelity compared to the CAD model, and good pore interconnection was observed through microCT investigation. Mechanical compression and torsion tests were performed to verify that the mechanical properties of the 3D PCL/TPU structure were adequate. The 3D structure exhibited elastic moduluses comparable to those of the cartilaginous and adipose parts of the auricle. The torsion tests showed the adequacy of the structure without detachment between TPU and PCL printed layers. In vitro cell viability tests confirmed the absence of cytotoxicity in both materials. The PCL/TPU layered scaffold reproduced the anatomy of the patient's healthy contralateral ear, representing a good compromise between flexibility and strength. This, along with the other assessed properties, make this scaffold a valid alternative for the reconstruction of the external ear.

• Gomes, Maria Clara; Mortier, Claudio; Haugen, Håvard Jostein; Blaker, Jonathan James & Mano, João F. (2025). Synergistic effect of proteins and tannic acid-yielding systems with improved mechanical performance for use in load-bearing tissues. Materials Research Express. doi: 10.1088/2053-1591/adee7e. Full text in Research Archive Show summary

  Developing bioactive hydrogels with mechanical properties resembling those of load-bearing connective tissues remains a significant challenge in the biomedical field. In this study, we address this limitation by incorporating human platelet lysate (PL) proteins, tannic acid (TA), and chitosan methacrylate (CHI-MA) to formulate reinforced hydrogel systems with markedly improved mechanical performance. The resulting PL/CHI-MA/TA hydrogels exhibit exceptional mechanical characteristics, attaining strengths of approximately 7 MPa and stiffness values of 5 MPa—comparable to those found in load-bearing tissues such as cartilage. This improvement can be attributed to the synergistic effect, which enhances the interaction between PL proteins and the polymeric network, thereby increasing strength, toughness, and efficient energy dissipation. Moreover, these hydrogels support the adhesion and proliferation of human-derived adipose stem cells, underscoring their potential utility in tissue engineering and regenerative medicine applications targeting load-bearing connective tissues, such as cartilage

• Haugen, Håvard Jostein; Bueno, Jaime; Hussain, Badra; Raquel, Osorio & Alonso, Mariano Sanz (2025). Comparative study of polymeric nanoparticles and traditional agents in dental implant decontamination. Journal of Applied Biomaterials & Functional Materials (JABFM). 23. doi: 10.1177/22808000251313948. Full text in Research Archive Show summary

  Peri-implant diseases, such as peri-implantitis, affect up to 47% of dental implant recipients, primarily due to biofilm formation. Current decontamination methods vary in efficacy, prompting interest in polymeric nanoparticles (NPs) for their antimicrobial and protein-specific cleaning properties. We focused on removing pellicle layers and their ability to resist recontamination, comparing their performance against established decontamination agents. This study evaluated the efficacy of polymeric nanoparticles (NPs) in decontaminating titanium dental implants by removing proteinaceous pellicle layers and resisting recontamination. Titanium discs were treated with saline water, PrefGel®, hydrogen peroxide (H2O2), GUM® Paroex®, or polymeric NPs, and analysed using SEM, EDX, XPS, and contact angle measurements to assess changes in surface composition, morphology, and hydrophilicity. Polymeric NPs significantly reduced nitrogen levels compared to PrefGel® (mean reduction: 2.6%, p < 0.05), indicating effective protein removal. However, their carbon reduction efficacy was similar to that of other agents. SEM images revealed that polymeric NPs disaggregated larger protein aggregates but did not fully decontaminate the surface. Contact angle analysis showed changes in hydrophilicity consistent with other treatments. Hydrogen peroxide performed best overall, achieving the lowest carbon levels post-recontamination (mean reduction: 13%, p < 0.01). While polymeric NPs exhibited unique protein-specific cleaning potential, their overall performance was comparable to traditional agents. Residual contaminants, including carbon and oxygen, persisted on all treated surfaces, indicating enhanced cleaning strategies were needed. These findings highlight the potential of polymeric NPs as an innovative approach to implant decontamination, particularly for protein-specific biofilm control. While polymeric nanoparticles introduce a novel approach to dental implant decontamination, particularly in protein removal, their overall efficacy matches existing methods, although hydrogen peroxide performed better. This research, with its thoroughness and attention to detail, instils confidence in the audience about the reliability of the research findings

• Gajski, Petra; Par, Matej; Haugen, Håvard Jostein; Hildebrand, Torben; Zheng, Kai & Boccaccini, Aldo R [Show all 8 contributors for this article] (2025). Long-Term Water Immersion of Dental Composites Based on Bioactive Glass Influence on Sorption, Solubility, and Porosity. Scientific Reports. 15, p. 18857–18857. doi: 10.1038/s41598-025-04143-9. Full text in Research Archive Show summary

  This study investigated the effect of copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) on water sorption, solubility and porosity of an experimental dental composite over 180 days of water immersion, comparing it to bioactive glass 45S5 (BG) or inert fillers. Composites contained 35wt% Bis-GMA/TEGDMA resin (60/40), 55wt% silanised barium-glass fillers, and 10wt% of either Cu-MBGN (10-CuBG), 45S5 bioactive glass (10-BG), or inert silica nanofillers (10-Si). Both BG composites showed a higher mass increase during water immersion than inert control (10-Si) at all measured time points (p < 0.001), ranked as 10-BG > 10-CuBG > 10-Si. After 30 days, 10-BG had the greatest mass increase (4.02 ± 0.21%), followed by a decline until 180 days, while 10-CuBG (1.67 ± 0.10%) and 10-Si (1.19 ± 0.07%) showed gradual mass increases until the end of the measurement. 10-BG displayed higher water sorption and solubility than other materials, while 10-CuBG had the highest porosity parameters. While 10-BG and 10-Si showed significant increases in both total and open porosity after water immersion, no such changes were observed for 10-CuBG. The pore characteristics of dry specimens did not affect final water sorption and solubility after 180 days of water immersion. The Cu-MBGN composite had a lower mass increase than commercial BG and met ISO 4049 standards for both water sorption and solubility.

• Santos, Lúcia F.; Mendes, Maria C; Pereira, Joao F; Dias, Isabel R; Viegas, Carlos A & Amorim, Carlos O [Show all 11 contributors for this article] (2025). Remote-Controlled Magnetic Stimulation of Cell-Based Bioengineered Tissues for In Situ Bone Regeneration. Advanced Materials. ISSN 0935-9648. doi: 10.1002/adma.202500657. Full text in Research Archive Show summary

  The native cell microenvironment activates signaling pathways through mechanotransduction mechanisms, influencing cells’ physiological and functional outcomes. Magnetic fields are explored to manipulate these environments, and magnetic nanoparticles (MNPs) are highlighted as nano-instructive agents capable of activating key signaling pathways, presenting exciting possibilities in tissue engineering. Still, the ability to precisely control the assembly and differentiation of stem cells within a dynamically responsive microenvironment, crucial for effective tissue regeneration, remains unexplored. This study showcases a novel method wherein MNPs facilitate the precise assembly of magnetically responsive cells into complex 3D tissue structures upon internalization and exposure to temporally defined cyclic magnetic fields. By remotely stimulating these constructs, it is demonstrated for the first time the possibility of remote-controlled modulation of stem cell fate in vivo without biochemical supplementation. Notably, this approach led to ectopic bone formation, highlighting the ability of magnetic actuation to drive osteogenesis in non-bone environments. MNP-driven mechanical stimulation of implanted tissues functions as a bioresponsive system guiding osteogenic differentiation of human adipose-derived stem cells. The in vivo model further illustrates accelerated construct integration, enhanced osteogenic differentiation, and minimal local inflammation, underscoring the potential of this less invasive, remotely controllable platform to advance regenerative strategies for bone

• Lauretis, Angela de; Santacroce, Marco; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter; Linke, Dirk & Haugen, Håvard Jostein (2025). Surface-specific outcomes of mechanical debridement with titanium, chitosan and nitinol brushes on titanium dental implant surfaces. Journal of Dentistry. ISSN 0300-5712. doi: 10.1016/j.jdent.2025.106010. Full text in Research Archive Show summary

  Objectives Dental implants are susceptible to peri‑implant inflammation caused by bacterial biofilms, with surface properties playing a key role in bacterial adhesion and osseointegration. While mechanical debridement is essential for biofilm removal, consensus on the optimal tool remains limited. In this study, we evaluate the impact of a titanium, a chitosan and a nitinol brush on the surface properties of four titanium dental implant surfaces: OsseoSpeed®-like, SLActive®-like, machined, and polished. Methods Profilometry, contact angle measurements, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) were used to assess the surface properties and chemistry. Results SEM and profilometry revealed that the titanium and nitinol brushes altered the morphology and topography of the rough OsseoSpeed®-like and SLActive®-like surfaces, while these effects were less pronounced on machined surfaces. Conversely, the chitosan brush caused minimal changes, but its bristles wore down quickly by physical abrasion, increasing surface carbon as detected by EDX and identified by XPS as organic material. Conversely, XPS confirmed that carbon contamination in samples treated with metal brushes was primarily environmental. The increased hydrophobicity observed across all groups was linked to carbon contamination. Polished surfaces remained unaffected by mechanical debridement. Conclusions The chitosan brush showed minimal surface alterations, but the rapid bristle wear left organic residues that increased hydrophobicity. The titanium and nitinol brushes caused more pronounced surface changes, while contributing to increased hydrophobicity through environmental carbon contamination during debridement. Clinical significance Dental implant surface properties, including topography, morphology, wettability, and surface chemistry, play a critical role in bacterial adhesion and osseointegration. Selecting an optimal mechanical debridement instrument requires balancing the effective removal of biofilm with the impact on the implant surface properties.

• Palombo, David; Rivara, Federico; Nogueira, Liebert Parreiras; Vignoletti, Fabio; Esporrin, Javier Sanz & Haugen, Håvard Jostein [Show all 7 contributors for this article] (2025). Three-Dimensional Hard And Soft Tissue Healing At Implants With A Modified Neck Design: An In Vivo Preclinical Study. Clinical Implant Dentistry and Related Research. ISSN 1523-0899. doi: 10.1111/cid.70065. Full text in Research Archive
• Hildebrand, Torben; Haugen, Håvard Jostein; Romandini, Mario; Plotino, Gianluca & Nogueira, Liebert Parreiras (2025). From Pulp to Cementum: 3D Visualization of Soft and Hard Dental Tissues Using Different Micro-CT Contrast-Enhancement Techniques. International Endodontic Journal. ISSN 0143-2885. doi: 10.1111/iej.14260. Full text in Research Archive Show summary

  Aim: To determine the effect of two contrast-enhancement strategies in nano-computed tomography (nano-CT) imaging on the contrast-to-noise ratio (CNR) of various dental tissues, including pulp, dentine and cementum, with the goal of enhancing the visibility of dental soft tissues to a level not yet reported in laboratory nano-CT imaging. Methodology: Ten sound human third molars underwent decalcification and subsequent treatment with Lugol’s iodine (n=5, Group 1) or phosphotungstic acid (PTA) treatment without prior decalcification (n=5, Group 2) for contrast enhancement. Imaging was performed using the laboratory nano-CT system Skyscan 2211 and the synchrotron radiation for medical physics (SYRMEP) beamline. CNRs were measured for pulpal tissue, dentine and cementum and nano-CT images were compared with classical histology, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDXS). Results: Group 1 significantly enhanced the contrast of pulp tissue, resulting in a 168.2 % increase due to decalcification and an additional 148.7 % increase after Lugol’s iodine treatment. Dentine exhibited higher contrast in Group 2, whereas cementum showed similar contrast across both groups. Laboratory nano-CT enabled the visualisation of detailed soft tissue structures, including nerves, blood vessels and odontoblasts within the pulp, but cementocytes remained not visibleinvisible. Conclusions: Decalcification followed by Lugol’s iodine treatment was superior for enhancing soft tissue contrast, especially for pulp visualisation. PTA without decalcification yielded better contrast for dentine and facilitated the visualisation of attached soft tissues, such as periodontal ligament and predentine. These findings provide insights into selecting the most appropriate protocol to optimise nano-CT imaging for specific dental tissue analyses, including the pulp.

• Tien, Nguyen D.; Geng, Tianxiang; Coelho, David José Caetano; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Blaker, Jonathan James [Show all 7 contributors for this article] (2025). Multilayer gradient chitosan fiber scaffolds for skin tissue regeneration with enhanced mechanical strength and cellular infiltration. Reactive & functional polymers. ISSN 1381-5148. 214. doi: 10.1016/j.reactfunctpolym.2025.106276. Full text in Research Archive Show summary

  Using the solution blow spinning technique, a trilayer structure scaffold was developed for skin tissue engineering. The scaffold, composed of chitosan/polyethylene oxide (CHI/PEO) fibers, mimicking the skin's natural structure, featuring a fiber diameter gradient ranging from 300 to 1200 nm and controlled porosity. Neutralization with potassium carbonate solution stabilized the chitosan-based fibers and enhanced their mechanical properties. The subsequent removal of PEO during neutralization created a porosity gradient (80–50%) across the scaffold layers, resulting in interconnected pores essential for cell infiltration and nutrient transport. The neutralized scaffolds enhanced mechanical performance with an ultimate tensile strength of 29.4 ± 4.8 MPa and Young’s modulus of 6.5 ± 1.1 MPa. The toughness was found to be 2.3 ± 1.0 MJ/m³. The gradient design closely mimics aspects of the skin's extracellular matrix. It substantially enhances the scaffold’s mechanical integrity—doubling tensile strength, Young’s modulus, and toughness compared to the as-spun structure—while preserving the essential flexibility required for dynamic wound environments. In vitro evaluations using co-cultures of normal human dermal fibroblasts (NHDF) and human epidermal keratinocytes (HEKa) demonstrated suitable cell viability, adhesion, and proliferation on the scaffold. Moreover, confocal imaging confirmed HEKa cellular infiltration throughout the more porous scaffold parts and dense NHDF layers on the less porous fiber layer, effectively mimicking the spatial organization of native skin layers. Our results underscore the significant potential of this gradient chitosan fiber scaffold as a scalable and versatile platform for skin tissue engineering. This innovative scaffold offers a promising new strategy for accelerating wound healing and achieving durable tissue regeneration by seamlessly integrating superior mechanical performance with enhanced cellular dynamics.

• Borie, Manon; Bosshardt, Dieter D.; LIEGEOIS, Lemmy; Lecloux, Geoffrey; Haugen, Håvard Jostein & HEDE, Dorien VAN [Show all 7 contributors for this article] (2025). Peri-Implant Supracrestal Tissue characteristics related to abutment materials : a comparative histomorphometry study. Clinical Implant Dentistry and Related Research. ISSN 1523-0899. 27(5). doi: 10.1111/cid.70083. Full text in Research Archive Show summary

  Background: The peri-implant soft tissue integration is critical to maintain peri-implant health and the long-term success of dental implant rehabilitations. Aim: This comparative histomorphometry study aims to characterize the peri-implant soft tissues (PIST) around experimental abutments made of titanium (Ti), dental resin (Re), and polyetheretherketone (PEEK). Methods: Thirty bone-level implants were placed, each received an experimental transmucosal healing abutment made of one of the three materials. After an 8-week healing period, the abutments and surrounding tissues were harvested and prepared for histological and histomorphometric analyses. Dimensions of sulcus depth, epithelial and connective tissue adhesion were measured. In addition, the abutment surface characteristics, levels of inflammation, plaque accumulation, and peri-implant bone level changes were evaluated. Results: The dimensions of the different component of the PIST were comparable across the three experimental groups. The mean overall dimensions of the PIST were 2.68± 0.51mm for Ti 2.66mm ± 0.47mm for Re and 2.32mm ± 0 .55mm for PEEK. Mean sulcus depth was 0.71± 0.69mm for Ti, 0.74± 0.50mm for Re and 0.68± 0.63mm for PEEK. Mean junctional epithelium was 1.82 ±0.67mm for Ti, 1.56± 0.47mm for Re and 1.53± 0.40mm for PEEK. Mean harvested connective tissue (until abutment platform) was 0.30± 0.29mm for Ti, 0.36± 0.38mm for Re and 0.09± 0.10mm for PEEK . However, the resin group exhibited significantly more supramucosal biofilm adhesion (p = 0.026). Conclusion: The PIST around abutments made of PEEK, resin, or titanium tend to develop in a similar pattern. However, longer observation periods are required to evaluate the long-term effects.

• Stickland, Joe Jacob; Schröer, Laurent; Buyse, Florian; Guedes, Alexandra; Haugen, Håvard Jostein & Mathiesen, Ragnvald [Show all 9 contributors for this article] (2025). Advanced microscopy probes for geomaterials – current state of the art and future perspectives. Tomography of Materials and Structures (JTMS). 9. doi: 10.1016/j.tmater.2025.100073. Full text in Research Archive Show summary

  Geomaterials form the basis of our planet. With structural features spanning from the nanometreto the continental-scale, geomaterials possess a complex but fascinating hierarchical structure that allows us to investigate their formation’s associated physical, chemical, and biological processes. Geomaterials provide us insights into the formation and evolution of the Earth as well as the origin of life as preserved in fossilised remains of microorganisms. Microscopy is perhaps the most powerful tool that helps us to appreciate and understand geomaterials. With rapid advances in experimental science during the last several decades, we can now image internal structures and follow internal dynamic processes in real-time in three dimensions. A wide range of current 3D imaging methodologies have emerged that help us understand and observe geomaterials’ relevant structural features. Attenuation-based 3D X-ray tomography is the most used micro-scale technique, which can be paired with complementary techniques to highlight more features and details within geomaterials. This review documents the relevant complementary microscopy modalities: phase contrast and diffraction contrast X-ray tomography, neutron tomography and electron tomography, and other methods like atom probe tomography and chemical- and structuralspecific Raman imaging. This review article aims to provide an overview of a wide range of microscopy methodologies (for researchers) and the insight that can be garnered from their use with geomaterials.

• Haugen, Håvard Jostein & Lange, Thomas de (2024). Multiple choice as formative assessment in dental education. European journal of dental education. ISSN 1396-5883. 28(3), p. 757–769. doi: 10.1111/eje.13002. Full text in Research Archive Show summary

  Introduction: The effectiveness of Multiple-Choice Questions (MCQs) in dental education is pivotal to student performance and knowledge advancement. However, their optimal implementation requires exploration to enhance the benefits. Materials and Methods: An educational tool incorporating MCQs was administered from the 5th to the 10th semester in a dental curriculum. The students filled out a questionnaire after the MCQ, which was linked to the Learning Management System. 4 cohorts of 4 semesters generated 2300 data points analysed by Spearmen correlation and mixed model regression analysis. Results demonstrated a significant correlation between early exam preparation and improved student performance. Independent study hours and lecture attendance emerged as significant predictors, accounting for approximately 10.27% of the variance in student performance on MCQs. While the number of MCQs taken showed an inverse relationship with study hours, the perceived clarity of these questions positively correlated with academic achievement. Conclusion: MCQs have proven effective in enhancing student learning and knowledge within the discipline. Our analysis underscores the important role of independent study and consistent lecture attendance in positively influencing MCQ scores. The study provides valuable insights into using MCQs as a practical tool for dental student learning. Moreover, the clarity of assessment tools, such as MCQs, remains pivotal in influencing student outcomes. This study underscores the multifaceted nature of learning experiences in dental education and the importance of bridging the gap between student expectations and actual performance.

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• 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.

• Lund, Ingrid Maria Castro; Reese, Jan-Ole; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Linke, Dirk (2025). Discovering the species-specific dynamics within a model biofilm system for peri-implantitis. Full text in Research Archive
• Reese, Jan-Ole; Lund, Ingrid Maria Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2025). Development of a flow-controlled biofilm model to facilitate the testing of debridement treatments of dental implant surfaces. Full text in Research Archive
• Lauretis, Angela de; Santacroce, Marco; Hussain, Badra; Ma, Qianli; Ellingsen, Jan Eirik & Lyngstadaas, Ståle Petter [Show all 8 contributors for this article] (2025). A poloxamer-peroxide forumulation effectively removes pellicle and limits recontamination. Full text in Research Archive

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