Qianli Ma

• Wang, Qiang; Jamous, Reem; Ma, Qianli; Linke, Dirk; Lyngstadaas, Ståle Petter & Saiz, Augustine Mark [Show all 12 contributors for this article] (2026). Early porcine wound responses to two application regimens of a hydrogen peroxide-poloxamer gel. Smart Materials in Medicine. 7, p. 536–551. doi: 10.1016/j.smaim.2026.10.004. Full text in Research Archive Show summary

  Hydrogen peroxide (H2O2) is widely used to reduce biofilm burden during implant-surface decontamination, but its reactivity creates a clinical trade-off between antimicrobial action and host-tissue injury. We compared early tissue responses to brief application followed by irrigation and removal versus application without planned removal of the same H2O2–Poloxamer formulation. In a porcine full-thickness wound model, wounds were largely closed at day 7. Brief application followed by irrigation and removal (Brief-removal) was associated with lower wound closure and higher TNF-α staining than Sham, but neither outcome differed significantly from application without planned removal (Retained-gel). Rete-ridge density was lower with Brief-removal than with both Sham and Retained-gel. Both regimens reduced local IL-10 expression. Exploratory proteomics screening suggested candidate host-response differences, but none of the 6981 protein groups met the false discovery rate threshold in the pig-adjusted analysis. Measurements suggested a decline in peroxide in recovered gel over the first 4 h in an ex vivo assay, whereas the gel matrix persisted for days in a separate vial system. These findings characterize early tissue responses to two application protocols but do not establish the underlying tissue H2O2 exposure profiles. Further studies linking tissue exposure, antimicrobial activity, and healing are needed before an application protocol can be recommended.

• 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.

• 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.

• 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.

• 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
• Li, Yi; Huang, Junling; Zhang, Yan; He, Yide; Cai, Dongxuan & Xu, Min [Show all 9 contributors for this article] (2025). LL-37—biofunctionalized titanium improves soft tissue seal surrounding the dental implant from the perspective of optimizing a race to the surface. Regenerative Biomaterials. 12. doi: 10.1093/rb/rbaf117. Full text in Research Archive
• 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.

• 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.

• Øvrebø, Øystein; Orlando, Luca; Rubenis, Kristaps; Ciriello, Luca; Ma, Qianli & Giorgi, Zoe [Show all 13 contributors for this article] (2024). The role of collagen and crystallinity in the physicochemical properties of naturally derived bone grafts. Regenerative Biomaterials. 11. doi: 10.1093/rb/rbae093. Full text in Research Archive Show summary

  Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinises them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100 °C (Sintered) using advanced microscopy, spectroscopy, x-ray analysis, and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids, or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Micro computed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size, and strut size. Additionally, scanning electron microscopy (SEM) displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa, and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.

• Hildebrand, Torben; Ma, Qianli; Loča, Dagnija; Rubenis, Kristaps; Locs, Janis & Nogueira, Liebert Parreiras [Show all 7 contributors for this article] (2024). Improved visualisation of ACP-engineered osteoblastic spheroids: a comparative study of contrast-enhanced micro-CT and traditional imaging techniques. Biofabrication. ISSN 1758-5082. 17(1). doi: 10.1088/1758-5090/ad8bf5. Full text in Research Archive Show summary

  This study investigates osteoblastic cell spheroid cultivation methods, exploring flat-bottom, U-bottom, and rotary flask techniques with and without amorphous calcium phosphate (ACP) supplementation to replicate the 3D bone tissue microenvironment. ACP particles derived from eggshell waste exhibit enhanced osteogenic activity in 3D models. However, representative imaging of intricate 3D tissue-engineered constructs poses challenges in conventional imaging techniques due to notable scattering and absorption effects in light microscopy, and hence limited penetration depth. We investigated contrast-enhanced micro-CT as a methodological approach for comprehensive morphological 3D-analysis of the in-vitro model and compared the technique with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and classical histology. Phosphotungstic acid (PTA) and iodine-based contrast agents were employed for micro-CT imaging in laboratory and synchrotron micro-CT imaging. Results revealed spheroid shape variations and structural integrity influenced by cultivation methods and ACP particles. The study underscores the advantage of 3D spheroid models over traditional 2D cultures in mimicking bone tissue architecture and cellular interactions, emphasising the growing demand for novel imaging techniques to visualise 3D tissue-engineered models. Contrast-enhanced micro-CT emerges as a promising non-invasive imaging method for tissue-engineered constructs containing ACP particles, offering insights into sample morphology, enabling virtual histology before further analysis.

• Ma, Qianli; Piaia, Lya; Loča, Dagnija; Rubenis, Kristaps; Locs, Janis & Thiede, Bernd [Show all 8 contributors for this article] (2024). Soluble Proteins From Conventional and Organic Eggshell Membranes With Different Proteomic Profiles Show Similar In Vitro Biofunctions. Journal of Biomedical Materials Research. Part A. ISSN 1549-3296. 113(1). doi: 10.1002/jbm.a.37848. Full text in Research Archive Show summary

  The eggshell membrane (ESM), resembling the extracellular matrix, acts as a protective barrier against bacterial invasion and offers various biofunctions due to its porous structure and protein-rich composition, such as ovalbumin, ovotransferrin, collagen, soluble protein, and antimicrobial proteins. However, ESM's structure primarily comprises disulfide bonds and heterochains, challenging protein solubilization/extraction. Therefore, the method of dissolving and extracting bioactive protein components in ESM has extremely high potential value and importance for exploring the reuse of egg waste and environmental protection. In this study we extracted soluble ESM proteins (SEPs) from conventional (industrial-fed) and organic (free-grounded) using an acidic 3-mercaptopropionic acid (3-MPA) extraction strategy. FTIR was used to monitor the chemical changes in the ESM, and LC-MS/MS was employed to conduct the proteomic analysis. The biocompatibility and the effects of SEPs cocktails on extracellular matrix (ECM) synthesis were also investigated. The results indicated that the acidic 3-MPA strategy could effectively alter the ESM chemical composition, thereby facilitating SEPs extraction. The SEPs from conventional and organic eggs have different protein profiles but with partial overlapping. SEPs from different sources exhibited similarly desirable biosafety profiles and similar dose-dependent promotion of osteoblastic (ECM) component synthesis, suggesting that different egg sources may contribute to consistent core biological functions of protein products but may also introduce different functional priorities

• Haugen, Håvard Jostein; Ma, Qianli; Linskens, Stefanie; Par, Matej; Mandic, Visnja Negovetic & Mensikova, Emile [Show all 13 contributors for this article] (2024). 3D micro-CT and O-PTIR spectroscopy bring new understanding of the influence of filler content in dental resin composites. Dental Materials. ISSN 0109-5641. doi: 10.1016/j.dental.2024.09.001. Full text in Research Archive Show summary

  Background Dental resin composites' performance is intricately linked to their polymerisation shrinkage characteristics. This study compares polymerisation shrinkage using advanced 3D micro-computed tomography (micro-CT) and traditional 2D linear assessments. It delves into the crucial role of filler content on shrinkage and the degree of conversion in dental resin composites, providing valuable insights for the field. Methods Five experimental dental composite materials were prepared with increasing filler contents (55–75 wt%) and analysed using either 3D micro-CT for volumetric shrinkage or a custom-designed linometer for 2D linear shrinkage. The degree of conversion was assessed using Optical Photothermal Infrared (O-PTIR) and Fourier-Transform Infrared (FTIR) spectroscopy. Light transmittance through a 2-mm layer was evaluated using a NIST-calibrated spectrometer. Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray Spectroscopy (EDX) examined surface morphology and elemental distribution. Correlation between the investigated parameters was determined using Spearman correlation analyses. Results The study found significant differences in polymerisation-related properties among different filler content categories, with volumetric shrinkage consistently demonstrating higher mean values than linear shrinkage across most groups. Volumetric shrinkage decreased with increasing curing depth, showing no direct correlation between filler content and shrinkage levels at different curing depths. The results highlighted a strong negative correlation between filler content and degree of conversion, volumetric and linear shrinkage, as well as maximum shrinkage rate. Light transmittance showed a moderate correlation with the filler content and a weak correlation with other tested parameters. Conclusions This study underscores the importance of considering both volumetric and linear shrinkage in the design and analysis of dental composite materials. The findings advocate optimising filler content to minimise shrinkage and enhance material performance. Integrating micro-CT and O-PTIR techniques offers novel insights into dental composites' polymerisation behaviour, providing a foundation for future research to develop materials with improved clinical outcomes.

• Marovic, Danijela; Haugen, Håvard Jostein; Par, Matej; Linskens, Stefanie; Mensikova, Emile & Mandic, Visnja Negovetic [Show all 10 contributors for this article] (2024). Emerging technologies for the evaluation of spatio-temporal polymerisation changes in flowable vs. sculptable dental resin-based composites. Dental Materials. ISSN 0109-5641. doi: 10.1016/j.dental.2024.09.002. Full text in Research Archive Show summary

  Background: This study presents a novel multi-technique approach that integrates micro-CT and optical photothermal infrared spectroscopy (O-PTIR) to evaluate polymerisation differences, so-called spatio-temporal polymerisation properties, between flowable and sculptable dental resin-based composites. Methods: Ten commercially available dental composites were investigated, including flowable and sculptable counterparts from the same manufacturer. Eight parameters were evaluated: short-term polymerisation characteristics (degree of conversion after 5 min, maximum polymerisation rate, time to reach maximum polymerisation rate) was measured using ATR-FTIR with real-time monitoring; changes in the degree of conversion with depth were evaluated with O-PTIR, 3D visualisation of shrinkage patterns, overall volumetric shrinkage, depth-specific shrinkage, and porosity were measured using micro-CT; surface morphology with detailed measurements of elemental composition was characterised using SEM/EDX; light transmittance was analysed with a NIST-referenced spectrometer. Results: The study found that the increase in filler weight and volume ratio reduced the degree of conversion and polymerisation shrinkage, while moderately influencing the maximum polymerisation rates. The time to reach maximum polymerisation rates and light transmittance were not dependent on the filler amount. OPTIR assessed a depth-dependent decrease in the degree of conversion for both composite types, with flowable composites generally showing a greater decrease in the degree of conversion than sculptable composites, except for bulk-fill composites. Micro-CT scans showed significantly higher flowable shrinkage values than their sculptable counterparts, highlighting the performance differences between the two types of composites. Conclusions: The findings of this study have practical implications for the selection and use of dental composites. Flowable composites, despite their higher degrees of conversion and polymerisation rates, also exhibit higher volumetric shrinkage, which can be detrimental for clinical applications. The new measurement methods used in this study provide a comprehensive overview of the polymerisation behaviour of commercially available dental composites, offering valuable insights for material optimisation.

• Øvrebø, Øystein; Giorgi, Zoe; Lauretis, Angela De; Vanoli, Valeria; Castiglione, Franca & Briatico-Vangosa, Francesco [Show all 10 contributors for this article] (2024). Characterisation and biocompatibility of crosslinked hyaluronic acid with BDDE and PEGDE for clinical applications. Reactive & functional polymers. ISSN 1381-5148. 200. doi: 10.1016/j.reactfunctpolym.2024.105920. Full text in Research Archive Show summary

  Hyaluronic acid (HA) is a versatile biomaterial frequently utilized in regenerative medicine due to its gel-like properties, making it well-suited for clinical applications. However, its linear form is susceptible to rapid enzymatic degradation, limiting its longevity within the body. To address this challenge, extensive research has focused on crosslinking mechanisms to enhance the durability of HA gels. One early approach involved crosslinking HA with 1,4-butanediol diglycidyl ether (BDDE) to create HA-BDDE, a clinically used product since the 1990s. However, the manufacturing process for HA-BDDE, primarily used in industry, lacks comprehensive documentation in the literature. More recently, poly(propylene glycol) diglycidyl ether (PEGDE) has emerged as an alternative to BDDE for crosslinking, offering improved gel elasticity and reduced cytotoxicity. In this study, we present the manufacturing process for producing both crosslinked gels, HA-BDDE and HA-PEGDE, with negligible residual crosslinkers, as confirmed by FTIR and NMR analysis. We characterize the crosslinking kinetics and the resulting formulations, revealing that HA-PEGDE gel exhibits comparable stiffness (G' = 60 Pa vs. 75 Pa) to HA-BDDE, despite a lower effective crosslinking ratio (CrR = 0.12 vs. 0.24). Intriguingly, our cytotoxicity testing demonstrates significantly greater cell viability for HA-PEGDE compared to HA-BDDE (151% versus 108%). Overall, both gels can be readily manufactured using a similar process and demonstrate excellent in vitro biocompatibility. This study elucidates why HA-BDDE is widely utilized in clinical settings and underscores the potential promise of HA-PEGDE as an emerging variant for clinical applications.

• Hildebrand, Torben; Ma, Qianli; Heyward, Catherine Anne; Haugen, Håvard Jostein & Nogueira, Liebert Parreiras (2024). Advanced soft tissue visualization in conjunction with bone structures using contrast-enhanced micro-CT. Journal of Medical Imaging. ISSN 2329-4302. 11(6). doi: 10.1117/1.JMI.11.6.066001. Full text in Research Archive Show summary

  Purpose: Micro-CT analysis of soft tissues alongside bone remains challenging due to significant differences in X-ray absorption, preventing spatial inspection of bone remodeling including the cellular intricacies of mineralized tissues in developmental biology and pathology. The goal was to develop a protocol for contrast-enhanced micro-CT imaging that effectively visualizes soft tissues and cells in conjunction with bone while minimizing bone attenuation by decalcification. Approach: Murine femur samples were decalcified in EDTA and treated with three different contrast agents: i) iodine in ethanol, ii) PTA in water, and iii) Lugol’s iodine. Micro-CT scans were performed in the laboratory set-up SkyScan 1172 and at the SYRMEP beamline in ELETTRA. Soft- and hard-tissue contrast-to-noise ratio (CNR) and contrast efficiency after decalcification were measured. Results: In laboratory micro-CT, Lugol’s iodine demonstrated a three-times higher CNR in bone marrow, representing the soft tissue portion, compared to bone. Contrast efficiencies, measured in synchrotron micro-CT, were consistent with these findings. Higher resolutions and the specificity of Lugol’s iodine to cellular structures enabled detailed visualization of bone-forming cells in the epiphyseal plate. Conclusions: The combination of decalcification and the utilization of the contrast agent Lugol’s iodine facilitated an enhanced soft tissue visualization in conjunction with bone.

• Øvrebø, Øystein; Lauretis, Angela De; Ma, Qianli; Perale, Giuseppe; Nilsen, Ola & Rossi, Filippo [Show all 7 contributors for this article] (2024). Towards bone regeneration: Understanding the nucleating ability of proline-rich peptides in biomineralisation. Biomaterials Advances. ISSN 2772-9516. 159. doi: 10.1016/j.bioadv.2024.213801. Full text in Research Archive Show summary

  Obtaining rapid mineralisation is a challenge in current bone graft materials, which has been attributed to the difficulty of guiding the biological processes towards osteogenesis. Amelogenin, a key protein in enamel formation, inspired the design of two intrinsically disordered peptides (P2 and P6) that enhance in vivo bone formation, but the process is not fully understood. In this study, we have elucidated the mechanism by which these peptides induce improved mineralisation. Our molecular dynamics analysis demonstrated that in an aqueous environment, P2 and P6 fold to interact with the surrounding Ca2+, PO4 3− and OH− ions, which can lead to apatite nucleation. Although P2 has a less stable backbone, it folds to a stable structure that allows for the nucleation of larger calcium phosphate aggregates than P6. These results were validated experimentally in a concentrated simulated body fluid solution, where the peptide solutions accelerated the mineralisation process compared to the control and yielded mineral structures mimicking the amorphous calcium phosphate crystals that can be found in lamella bone. A pH drop for the peptide groups suggests depletion of calcium and phosphate, a prerequisite for intrinsic osteoinduction, while S/TEM and SEM suggested that the peptide regulated the mineral nucleation into lamella flakes. Evidently, the peptides accelerate and guide mineral formation, elucidating the mechanism for how these peptides can improve the efficacy of P2 or P6 containing devices for bone regeneration. The work also demonstrates how experimental mineralisation study coupled with molecular dynamics is a valid method for understanding and predicting in vivo performance prior to animal trials

• Ma, Qianli; Rubenis, Kristaps; Sigurjonsson, Olafur E.; Hildebrand, Torben; Standal, Therese & Zemjane, Signe [Show all 9 contributors for this article] (2023). Eggshell-derived amorphous calcium phosphate: Synthesis, characterization and bio-functions as bone graft materials in novel 3D osteoblastic spheroids model. Smart Materials in Medicine. 4, p. 522–537. doi: 10.1016/j.smaim.2023.04.001. Full text in Research Archive Show summary

  A multitude of autogenous/allogeneic and semi-synthetic bone graft materials have been developed to reconstruct the defective bone tissue but with high bio-cost and potential environmental pollution. With high calcium content and several trace elements, chicken eggshells are no longer considered as wastes but attractive sources of high-value-added biomaterials. This study used chicken eggshells and synthetic hydroxyapatite (HAp) to synthesize amorphous calcium phosphate (ACP) bone graft materials, namely Control and Eggshell. The physiochemical characteristics, biosafety, and immunocompatibility of synthetic ACP particles were inspected. Their osteogenic activity was further investigated in a novel osteoblastic spheroids model. Eggshell ACP particles exhibited ideal cytocompatibility compared to the control ACP and were more resistant to re-crystallization. In osteoblastic spheroids, Eggshell ACP mediated typical osteogenic mRNA profiles of MC-3T3-E1 cells, accompanied by the increased formation of mineralized nodules and boosted synthesis of ECM proteins represented by OPN and collagen I. This study establishes a promising technique to synthesize stable, safe, and osteoinductive ACP graft particles from eggshell waste. Furthermore, the osteoblastic spheroids constructed in the present study provide a more practical model for biomaterial research, which reflect the three-dimensional interaction between host bone tissue and graft materials more realistically.

• Ma, Qianli; Miri, Zahra; Haugen, Håvard Jostein; Moghanian, Amirhossein & Loca, Dagnija (2023). Significance of mechanical loading in bone fracture healing, bone regeneration, and vascularization. Journal of Tissue Engineering. 14. doi: 10.1177/20417314231172573. Full text in Research Archive Show summary

  In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed

• Miri, Zahra; Haugen, Håvard Jostein; Loča, Dagnija; Rossi, Filippo; Perale, Giuseppe & Moghanian, Amirhossein [Show all 7 contributors for this article] (2023). Review on the strategies to improve the mechanical strength of highly porous bone bioceramic scaffolds. Journal of the European Ceramic Society. ISSN 0955-2219. doi: 10.1016/j.jeurceramsoc.2023.09.003. Full text in Research Archive Show summary

  Bone healing is an impressive ability of the human body, but critical-sized bone defects require external intervention. Bioceramic scaffolds with excellent biocompatibility and bioactivity have been developed to treat non-healing bone defects because of their unique features for bone repair. Meanwhile, the mechanical properties of the material continue to be disadvantageous. This review focuses on (i) essential factors in affecting and improving bioceramic-based scaffolds' mechanical properties, including porosity, pore size, methods, and material composition, and (ii) summarizing previous studies and highlighting strategies to fabricate scaffolds with improved mechanical properties such as using nano-particles, using a combination of bioceramics and polymers, and modifying scaffold surfaces. Further research is necessary to improve bioceramic scaffolds for bone repair applications

• Goa, Hui; Jiang, Nan; Niu, Qiannan; Mei, Shenglin; Haugen, Håvard Jostein & Ma, Qianli (2023). Biocompatible nanostructured silver-incorporated implant surfaces show effective antibacterial, osteogenic, and anti-inflammatory effects in vitro and in rat model. International Journal of Nanomedicine. ISSN 1176-9114. 18, p. 7359–7378. doi: 10.2147/IJN.S435415. Full text in Research Archive Show summary

  Introduction: Titanium (Ti) and its alloys are widely utilized in endosseous implants. However, their clinical efficacy is marred by complications arising from bacterial infections owing to their inadequate antibacterial properties. Consequently, enhancing the antibacterial attributes of implant surfaces stands as a pivotal objective in the realm of implantable materials research. Methods: In this study, we employed sequential anodization and plasma immersion ion implantation (PIII) technology to fabricate a silver-embedded sparsely titania nanotube array (SNT) on the near-β titanium alloy Ti-5Zr-3Sn-5Mo-15Nb (TLM) implants. The surface characteristics, antimicrobial properties, biocompatibility, and osteogenic activity of the silver-nanomodified SNT implant (SNT Ag) surface, alongside peri-implant inflammatory responses, were meticulously assessed through a combination of in vitro and in vivo analyses. Results: Compared with polished TLM and SNT, the silver-embedded SNT (SNT Ag) surface retained the basic shape of nanotubes and stably released Ag+ at the ppm level for a long time, which demonstrated an effective inhibition and bactericidal activity against Staphylococcus aureus (SA) while maintaining ideal cytocompatibility. Additionally, the subtle modifications in nanotubular topography induced by silver implantation endowed SNT Ag with enhanced osteogenic activity and mitigated inflammatory capsulation in soft tissue peri-implants in a rat model. Conclusions: The incorporation of a silver-embedded SNT array onto the implant surface demonstrated robust antibacterial properties, impeccable cytocompatibility, exceptional osteogenic activity, and the potential to prevent inflammatory encapsulation around the implant site. The Silver-PIII modification strategy emerges as a highly promising approach for surface applications in endosseous implants and trans-gingival implant abutments.

• Ødegaard, Kristin Sirnes; Westhrin, Marita; Afif, Abdulla Shaikh Abdul Qader Bin; Ma, Qianli; Mela, Petra & Standal, Therese [Show all 8 contributors for this article] (2023). The effects of surface treatments on electron beam melted Ti-6Al-4V disks on osteogenesis of human mesenchymal stromal cells. Biomaterials Advances. ISSN 2772-9516. 147. doi: 10.1016/j.bioadv.2023.213327. Full text in Research Archive
• Miri, Zahra; Farè, Silvia; Ma, Qianli & Haugen, Håvard Jostein (2023). Updates on polyurethane and its multifunctional applications in biomedical engineering. Progress in Biomedical Engineering. 5(4). doi: 10.1088/2516-1091/acef84. Full text in Research Archive Show summary

  Polyurethanes (PU) have properties that make them promising in biomedical applications. PU is recognized as one of the main families of blood and biocompatible materials. PU plays a vital role in the design of medical devices in various medical fields. The structure of PU contains two segments: soft and hard. Its elastomeric feature is due to its soft segment, and its excellent and high mechanical property is because of its hard segment. It is possible to achieve specific desirable and targeted properties by changing the soft and hard chemical structures and the ratio between them. The many properties of PU each draw the attention of different medical fields. This work reviews PU highlighted properties, such as biodegradability, biostability, shape memory, and improved antibacterial activity. Also, because PU has a variety of applications, this review restricts its focus to PU's prominent applications in tissue engineering (TE), cardiovascular medicine, drug delivery, and wound healing. In addition, it contains a brief review of PU's applications in biosensors and oral administration.

• Han, Jingyuan; Ma, Qianli; An, Yanxin; Wu, Fan; Zhao, Yuqing & Wu, Gaoyi [Show all 7 contributors for this article] (2023). The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces. Journal of Nanobiotechnology. 21(1), p. 277–306. doi: 10.1186/s12951-023-02017-8. Full text in Research Archive Show summary

  With the continuous innovation and breakthrough of nanomedical technology, stimuli-responsive nanotechnology has been gradually applied to the surface modification of titanium implants to achieve brilliant antibacterial activity and promoted osteogenesis. Regarding to the different physiological and pathological microenvironment around implants before and after surgery, these surface nanomodifications are designed to respond to different stimuli and environmental changes in a timely, efficient, and specific way/manner. Here, we focus on the materials related to stimuli-responsive nanotechnology on titanium implant surface modification, including metals and their compounds, polymer materials and other materials. In addition, the mechanism of different response types is introduced according to different activation stimuli, including magnetic, electrical, photic, radio frequency and ultrasonic stimuli, pH and enzymatic stimuli (the internal stimuli). Meanwhile, the associated functions, potential applications and developing prospect were discussion.

• Fu, Zhaoyue; Hou, Yongli; Haugen, Håvard Jostein; Chen, Xutao; Tang, Kang & Fang, Liang [Show all 10 contributors for this article] (2023). TiO2 nanostructured implant surface-mediated M2c polarization of inflammatory monocyte requiring intact cytoskeleton rearrangement. Journal of Nanobiotechnology. 21. doi: 10.1186/s12951-022-01751-9. Full text in Research Archive Show summary

  Background Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed. Results In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity. Conclusions To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity.

• He, Yide; Gao, Yuanxue; Ma, Qianli; Zhang, Xige; Zhang, Yumei & Song, Wen (2022). Nanotopographical cues for regulation of macrophages and osteoclasts: emerging opportunities for osseointegration. Journal of Nanobiotechnology. 20(1). doi: 10.1186/s12951-022-01721-1. Full text in Research Archive Show summary

  Nanotopographical cues of bone implant surface has direct influences on various cell types during the establishment of osseointegration, a prerequisite of implant bear-loading. Given the important roles of monocyte/macrophage lineage cells in bone regeneration and remodeling, the regulation of nanotopographies on macrophages and osteoclasts has arisen considerable attentions recently. However, compared to osteoblastic cells, how nanotopographies regulate macrophages and osteoclasts has not been properly summarized. In this review, the roles and interactions of macrophages, osteoclasts and osteoblasts at different stages of bone healing is firstly presented. Then, the diversity and preparation methods of nanotopographies are summarized. Special attentions are paid to the regulation characterizations of nanotopographies on macrophages polarization and osteoclast differentiation, as well as the focal adhesion-cytoskeleton mediated mechanism. Finally, an outlook is indicated of coordinating nanotopographies, macrophages and osteoclasts to achieve better osseointegration. These comprehensive discussions may not only help to guide the optimization of bone implant surface nanostructures, but also provide an enlightenment to the osteoimmune response to external implant.

• Kohtala, Sampsa; Nedal, Tonje Marie Vikene; Kriesi, Carlo Rene; Moen, Siv Helen; Ma, Qianli & Ødegaard, Kristin Sirnes [Show all 8 contributors for this article] (2022). Automated Quantification of Human Osteoclasts Using Object Detection. Frontiers in Cell and Developmental Biology. 10(941542). doi: 10.3389/fcell.2022.941542. Full text in Research Archive Show summary

  A balanced skeletal remodeling process is paramount to staying healthy. The remodeling process can be studied by analyzing osteoclasts differentiated in vitro from mononuclear cells isolated from peripheral blood or from buffy coats. Osteoclasts are highly specialized, multinucleated cells that break down bone tissue. Identifying and correctly quantifying osteoclasts in culture are usually done by trained personnel using light microscopy, which is time-consuming and susceptible to operator biases. Using machine learning with 307 different well images from seven human PBMC donors containing a total of 94,974 marked osteoclasts, we present an efficient and reliable method to quantify human osteoclasts from microscopic images. An open-source, deep learning-based object detection framework called Darknet (YOLOv4) was used to train and test several models to analyze the applicability and generalizability of the proposed method. The trained model achieved a mean average precision of 85.26% with a correlation coefficient of 0.99 with human annotators on an independent test set and counted on average 2.1% more osteoclasts per culture than the humans. Additionally, the trained models agreed more than two independent human annotators, supporting a more reliable and less biased approach to quantifying osteoclasts while saving time and resources. We invite interested researchers to test their datasets on our models to further strengthen and validate the results.

• Aass, Kristin Roseth; Mjelle, Robin; Kastnes, Martin Haugrud; Tryggestad, Synne Stokke; Brink, Luca Mare van den & Roseth, Ingrid Aass [Show all 19 contributors for this article] (2021). Intracellular IL-32 regulates mitochondrial metabolism, proliferation, and differentiation of malignant plasma cells. iScience. 25(1). doi: 10.1016/j.isci.2021.103605. Full text in Research Archive Show summary

  Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression is regulated by two different oxygen sensing systems; HIF1α and cysteamine dioxygenase (ADO), indicating that IL-32 may be involved in the response to hypoxia. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in three myeloma cell lines reduced cell survival and proliferation in vitro and in vivo. High-throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that cells depleted of IL-32 had perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors, and citrate. IL-32 was expressed in a subgroup of myeloma patients with inferior survival, and primary myeloma cells expressing IL-32 had a gene signature associated with immaturity, proliferation, and oxidative phosphorylation. In conclusion, we demonstrate a previously unrecognized role of IL-32 in the regulation of plasma cell metabolism.

• Ødegaard, Kristin Sirnes; Ouyang, Lingzi; Ma, Qianli; Buene, Glenn; Wan, Di & Elverum, Christer Westum [Show all 9 contributors for this article] (2021). Revealing the influence of electron beam melted Ti-6Al-4V scaffolds on osteogenesis of human bone marrow-derived mesenchymal stromal cells. Journal of Materials Science: Materials in Medicine. ISSN 0957-4530. 32(97). doi: 10.1007/s10856-021-06572-0. Full text in Research Archive Show summary

  Porous Titanium-6Aluminum-4Vanadium scaffolds made by electron beam-based additive manufacturing (AM) have emerged as state-of-the-art implant devices. However, there is still limited knowledge on how they influence the osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs). In this study, BMSCs are cultured on such porous scaffolds to determine how the scaffolds influence the osteogenic differentiation of the cells. The scaffolds are biocompatible, as revealed by the increasing cell viability. Cells are evenly distributed on the scaffolds after 3 days of culturing followed by an increase in bone matrix development after 21 days of culturing. qPCR analysis provides insight into the cells’ osteogenic differentiation, where RUNX2 expression indicate the onset of differentiation towards osteoblasts. The COL1A1 expression suggests that the differentiated osteoblasts can produce the osteoid. Alkaline phosphatase staining indicates an onset of mineralization at day 7 in OM. The even deposits of calcium at day 21 further supports a successful bone mineralization. This work shines light on the interplay between AM Ti64 scaffolds and bone growth, which may ultimately lead to a new way of creating long lasting bone implants with fast recovery times.

• Ma, Qianli; Jiang, Nan; Shuang, Liang; Fulin, Chen; Liang, Fang & Xian, Wang [Show all 8 contributors for this article] (2020). Functionalization of a clustered TiO2 nanotubular surface with platelet derived growth factor-BB covalent modification enhances osteogenic differentiation of bone marrow mesenchymal stem cells. Biomaterials. ISSN 0142-9612. 230, p. 119650–119650. doi: 10.1016/j.biomaterials.2019.119650. Full text in Research Archive Show summary

  A multitude of micro- and nano-surface structures have been developed to improve the clinical performance of endosseous titanium (Ti) implants. However, most of these surface structures only simulate the topographic elements on a micro- or nano-scale. In this study, a nano-micro hierarchical TiO2 clustered nanotubular structure was fabricated using anodization, and then functionalized with platelet derived growth factor-BB (PDGF-BB) using PhoA (11-hydroxyundecylphosphonic acid)/CDI (carbonyldiimidazole) chemistry. The resulting 3-dimensional spatial biomimetic structure, named NTPCP, exhibited negligible cytotoxicity and satisfactory bio-activity for host cells, and significantly enhanced the attachment as well as osteogenesis-related functions (early-stage proliferation, extracellular matrix synthesis and mineralization) of human bone marrow mesenchymal stem cells (bMSCs). We observed drastically elevated expression of osteocalcin (OCN), which mirrored prominent bone formation around the NTPCP implants in a rat model. This study establishes a novel strategy to improve the osseointegration of endosseous Ti implants via surface nano-topographic modification and bio-factor covalent functionalization.

• Ma, Qianli; Jiang, Nan; Liang, Shuang; Chen, Fulin; Fang, Liang & Wang, Xian [Show all 8 contributors for this article] (2019). Functionalization of a clustered TiO2 nanotubular surface with platelet derived growth factor-BB covalent modification enhances osteogenic differentiation of bone marrow mesenchymal stem cells. Biomaterials. ISSN 0142-9612. 230(119650). doi: 10.1016/j.biomaterials.2019.119650. Full text in Research Archive

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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.

• 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
• Lauretis, Angela de; Hussain, Badra; Ma, Qianli; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2024). A comparative evaluation of chemical decontamination products on the cleanliness of dental implant surfaces using a dental pellicle model. Full text in Research Archive Show summary

  Dental implants are widely employed for tooth replacement, but complications such as peri-implant infections may arise due to bacterial adhesion and biofilm formation, facilitated by the protein-rich salivary pellicle formed on the implant surface. Ensuring the cleanliness of the implant surface is crucial for long-term success and maintenance of peri-implant health.

• Hildebrand, Torben; Ma, Qianli; A, Heyward Catherine; Haugen, Håvard Jostein & Nogueira, Liebert Parreiras (2024). Advanced soft tissue visualization in conjunction with bone structures using contrast-enhanced micro-CT. Full text in Research Archive
• Ma, Qianli; Rubenis, Kristaps; Haugen, Håvard Jostein; Hildebrand, Torben; Sigurjonsson, Olafur E. & Locs, Janis [Show all 7 contributors for this article] (2024). Eggshell-derived Amorphous Calcium Phosphate: Synthesis, Characterization and Bio-functions as Bone Graft Materials in Novel 3d Osteoblastic Spheroidic Model. Full text in Research Archive
• Wang, Qiang; Ma, Qianli & Haugen, Håvard Jostein (2024). The in-vitro effects of different detergents on tissue regeneration around Ti implants. Full text in Research Archive
• Han, Jingyuan; Ma, Qianli; An, Yanxin; Wu, Fan; Zhao, Yuqing & Wu, Gaoyi [Show all 7 contributors for this article] (2023). Correction: The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces (Journal of Nanobiotechnology, (2023), 21, 1, (277), 10.1186/s12951-023-02017-8). Journal of Nanobiotechnology. 21(1). doi: 10.1186/s12951-023-02102-y. Full text in Research Archive
• Alam, Anam; Haugen, Håvard Jostein; Ma, Qianli & Loča, Dagnija (2023). USING EGGSHELLS FOR BONE GRAFTS. [Journal]. Springwise. Full text in Research Archive Show summary

  Bone grafts are considered to be the gold standard in terms of repairing and reconstructing damaged bones. These can either be autologous, where a patient’s own tissue is used, or allogeneic, where the tissue is taken from another person. But limited supply, donor-site complications, and risk of disease transmission can often prevent allogeneic grafts from being used. Xenogeneic bone grafts, where the graft is taken from another species, represent a feasible alternative. But, because xenograft materials come from mammal tissue, it raises ethical questions surrounding animal welfare. To find a safe, adaptable, and environmentally friendly alternative, a team of researchers has developed a method to convert eggshells into endotoxin-free and immunocompatible amorphous calcium phosphate (ACP) particles. First the shells were heated, then mixed with distilled water and phosphoric acid. The precipitate was then filtered and washed, before being submerged in liquid nitrogen. The resulting ACP particles are essential to forming hard and strong bone and can therefore be used as an ideal bone substitute. As well as containing plenty of calcium and phosphorous, Dr Qianli Ma – the study’s lead author – highlights that eggshells are also an ideal raw material because they contain traces of magnesium and strontium, which are associated with healthy bone regeneration. The team also created a novel 3D spheroid model, which allows the activity of eggshell ACP to be studied in vitro. With the model, the researchers could observe how the ACP materials would actually interact with osteoblasts, and they were found to be safe and effective in promoting bone regeneration. If scaled successfully, this new technique could enable an unlimited supply of sustainable bone graft materials, while reducing the volume of eggshells going to waste. The scientists hope their latest findings inspire additional research into the conversion of food waste into high-value biomaterials. Eggshells are not only being used in the medical field. Springwise has also spotted a design studio creating wall tiles from discarded eggshells, and another that has transformed the waste into car interiors

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