Hanna Tiainen

• Demir, Ali Aslan; Combriat, Thomas Michel Daniel; Heyward, Catherine Anne; Tiainen, Hanna; Carlier, Aurélie & Dysthe, Dag Kristian (2026). A cellular automaton model of osteogenic differentiation reveals identifiability limits of endpoint assays. Frontiers in Systems Biology. 6. doi: 10.3389/fsysb.2026.1872774. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Standard differentiation assays sample cell states only at discrete time points, while the underlying progression unfolds continuously and heterogeneously across cells. As a result, different combinations of proliferation, commitment, and maturation dynamics can converge to similar endpoint measurements. This many-to-one mapping between latent trajectories and observable readouts constitutes a partially observed inverse problem that limits mechanistic interpretation. Although this ambiguity is inherent to many experimental systems, it is rarely examined using models that connect cell-state dynamics to assay-level quantities. Methods We present OsteoMin, a coarse-grained cellular automaton that links stochastic transitions between pre-osteoblast and osteoblast states to experimentally measurable readouts of alkaline phosphatase activity, collagen deposition, and mineralization. Model parameters were constrained using literature-reported kinetics and evaluated against dexamethasone and menaquinone-4 perturbations. The framework enables systematic analysis of how cell-state progression, matrix maturation, and external perturbations shape differentiation outcomes. Results OsteoMin reproduces qualitative assay trends and quantifies the identifiability limits of endpoint assays. Distinct perturbation families often produce similar endpoint responses (macro-F1 ≈ 0.42$), indicating limited discriminative power. Incorporating temporal trajectories improves separability (macro-F1 ≈ 0.78$), demonstrating that most identifiable information resides in marker dynamics rather than terminal measurements. Sobol analysis shows that early markers depend on proliferation timing, whereas late mineralization is governed by nonlinear matrix maturation and parameter interactions. Discussion These results show that endpoint assays constrain overall progression but do not uniquely identify underlying mechanisms. OsteoMin provides a framework linking differentiation dynamics to assay observables and a basis for assessing identifiability in endpoint-driven systems.

• Raveendran, Dhanya; Dalloul, Feras; Mietner, J. Benedikt; Barba, Enguerrand; Chen, Shouzheng & Zaytseva-Zotova, Daria [Vis alle 12 forfattere av denne artikkelen] (2025). 3D Printable Hydrogel Based on TEMPO-Oxidized Cellulose Nanofibrils and Fmoc-FF for Enhanced Biological Performance and Cell Adhesion. ACS Applied Nano Materials. 8(38), s. 18571–18583. doi: 10.1021/acsanm.5c03356. Fulltekst i vitenarkiv Vis sammendrag

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

• Remartinez, Enrique Oreja; Zaytseva-Zotova, Daria; Rogala, Agnes; Bautista, Alejandro Barrantes; Messersmith, Phillip B. & Tiainen, Hanna (2025). Multifunctional tannic acid and polyamino acid layer-by-layer coatings for tailored implant surfaces. ACS Biomaterials Science and Engineering. 11(9), s. 5376–5388. doi: 10.1021/acsbiomaterials.5c00832. Fulltekst i vitenarkiv
• Rogala, Agnes; Tiainen, Hanna & Zaytseva-Zotova, Daria (2024). Using QCM-D for Real-Time Analysis of Cell Adhesion Dynamics at Biointerfaces. Advanced Materials Interfaces. doi: 10.1002/admi.202400811. Fulltekst i vitenarkiv Vis sammendrag

  Efficient cell adhesion is crucial for host tissue attachment and improving implant integration. This study aims at investigating adhesion of human gingival fibroblasts to functionalized biomaterial surfaces using quartz crystal microbalance with dissipation (QCM-D) and analyzing the dynamics of focal adhesion (FA) formation during this process. The QCM-D responses are correlated with changes in cell morphology and activation of focal adhesion kinase (FAK) in the absence or presence of serum proteins. As model surfaces, this work uses polystyrene oxidized by UV/ozone treatment (PSox) and tannic acid nanocoating formed on polystyrene (TA60). Compared to PSox, reduced cell adhesion on TA60 with fibroblast establishing fewer FAs is observed in this work. The addition of serum promotes more stable cell adhesion, although the adsorbed protein corona slows initial cell spreading and FAK activation. Further, this work examines whether there is a relationship between QCM-D responses and FAK activation. The data shows a positive correlation between the energy dissipation and temporal changes in phosphorylated FAK (pY397FAK), although the absolute value of pY397FAK cannot be derived from the QCM-D response. Thus, this study demonstrates the usefulness of the QCM-D as a technique for quantitative non-invasive analysis of cell adhesion to functionalized surfaces.

• Rogala, Agnes; Zaytseva-Zotova, Daria; Remartinez, Enrique Oreja; Bautista, Alejandro Barrantes & Tiainen, Hanna (2024). Combining QCM-D with live-cell imaging reveals the impact of serum proteins on the dynamics of fibroblast adhesion on tannic acid-functionalised surfaces. Biomaterials Science. ISSN 2047-4830. 12, s. 3345–3359. doi: 10.1039/d4bm00184b. Fulltekst i vitenarkiv Vis sammendrag

  Nanocoatings based on plant polyphenols have been recently suggested as a potent strategy for modification of implant surfaces for enhancing host cell attachment and reducing bacterial colonisation. In this study we aimed to investigate how serum proteins impact the early adhesion dynamics of human gingival fibroblasts onto titanium surfaces coated with tannic acid (TA). Silicate-TA nanocoatings were formed on titanium and pre-conditioned in medium supplemented with 0, 0.1, 1 or 10% FBS for 1 hour. Dynamics of fibroblasts adhesion was studied using quartz crystal microbalance with dissipation (QCM-D). Time-lapse imaging was employed to assess cell area and motility, while immunofluorescence microscopy was used to examine cell morphology and focal adhesion formation. Our results showed that in serum-free medium, fibroblasts demonstrated enhanced and faster adhesion to TA coatings compared to uncoated titanium. Increasing the serum concentration reduced cell adhesion to nanocoatings, resulting in nearly complete inhibition at 10% FBS. This inhibition was not observed for uncoated titanium at 10% FBS, although cell adhesion was delayed and progressed slower compared to serum-free conditions. In addition, 1% FBS dramatically reduced cell adhesion on uncoated titanium. We revealed a positive relationship between changes in dissipation and changes in cell spreading area, and a negative relationship between dissipation and cell motility. In conclusion, our study demonstrated that serum decreases fibroblasts interaction with surfaces coated with TA in a concentration dependent manner. This suggests that controlling serum concentration can be used to regulate or potentially prevent fibroblasts adhesion onto TA-coated titanium surfaces.

• Khan, Sadia Nazir; Koldsland, Odd Carsten; Tiainen, Hanna & Hjortsjö, Carl (2024). Anatomical three-dimensional model with peri-implant defect for in vitro assessment of dental implant decontamination. Clinical and Experimental Dental Research. 10(1). doi: 10.1002/cre2.841. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Objectives Access to the implant surface plays a significant role in effective mechanical biofilm removal in peri‐implantitis treatment. Mechanical decontamination may also alter the surface topography of the implant, potentially increasing susceptibility to bacterial recolonization. This in vitro study aimed to evaluate a newly developed, anatomically realistic, and adaptable three‐dimensional (3D)printed model with a peri‐implant bone defect to evaluate the accessibility and changes of dental implant surfaces after mechanical decontamination treatment. Material and Methods A split model of an advanced peri‐implant bone defect was prepared using 3D printing. The function of the model was tested by mechanical decontamination of the exposed surface of dental implants (Standard Implant Straumann AG) coated with a thin layer of colored occlusion spray. Two different instruments for mechanical decontamination were used. Following decontamination, the implants were removed from the split model and photographed. Image analysis and fluorescence spectroscopy were used to quantify the remaining occlusion spray both in terms of area and total amount, while scanning electron microscopy and optical profilometry were used to analyze alteration in the implant surface morphology. Results The 3D model allowed easy placement and removal of the dental implants without disturbing the implant surfaces. Qualitative and quantitative assessment of removal of the occlusion spray revealed differences in the mechanism of action and access to the implant surface between tested instruments. The model permitted surface topography analysis following the decontamination procedure. Conclusion The developed 3D model allowed a realistic simulation of decontamination of implant surfaces with colored occlusion spray in an advanced peri‐implant defect. 3D printing allows easy adaptation of the model in terms of the shape and location of the defect. The model presents a valuable tool for in vitro investigation of the accessibility and changes of the implant surface after mechanical and chemical decontamination.

• Printzell, Lisa; Reseland, Janne Elin; Edin, Nina Frederike Jeppesen; Ellingsen, Jan Eirik & Tiainen, Hanna (2023). Backscatter from therapeutic doses of ionizing irradiation does not impair cell migration on titanium implants in vitro. Clinical Oral Investigations. ISSN 1432-6981. doi: 10.1007/s00784-023-05128-6. Fulltekst i vitenarkiv Vis sammendrag

  Objective The influence of radiation backscatter from titanium on DNA damage and migration capacity of human osteoblasts (OBs) and mesenchymal stem cells (MSCs) may be critical for the osseointegration of dental implants placed prior to radiotherapy. In order to evaluate effects of radiation backscatter, the immediate DNA damage and migration capacity of OBs and MSCs cultured on titanium or plastic were compared after exposure to ionizing irradiation. Materials and methods Human OBs and MSCs were seeded on machined titanium, moderately rough fluoride-modified titanium, or tissue culture polystyrene, and irradiated with nominal doses of 2, 6, 10, or 14 Gy. Comet assay was performed immediately after irradiation, while a scratch wound healing assay was initiated 24 h post-irradiation. Fluorescent live cell imaging documented the migration. Results DNA damage increased with higher dose and with backscatter from titanium, and MSCs were significantly more affected than OBs. All doses of radiation accelerated the cell migration on plastic, while only the highest dose of 10 Gy inhibited the migration of both cell types on titanium. Conclusions High doses (10 Gy) of radiation inhibited the migration capacity of both cell types on titanium, whereas lower doses (2 and 6 Gy) did not affect the migration of either OBs or MSCs. Clinical relevance Fractionated doses of 2 Gy/day, as distributed in conventional radiotherapy, appear not to cause severe DNA damage or disturb the migration of OBs or MSCs during osseointegration of dental implants.

• Spoutil, Frantisek; Aranaz-Novaliches, Goretti; Prochazkova, Michaela; Wald, Tomas; Novosadova, Vendula & Kasparek, Petr [Vis alle 14 forfattere av denne artikkelen] (2023). Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions. Scientific Reports. 13(1). doi: 10.1038/s41598-023-28388-4. Fulltekst i vitenarkiv Vis sammendrag

  Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

• Munir, Arooj; Reseland, Janne Elin; Tiainen, Hanna; Haugen, Håvard Jostein; Sikorski, Pawel & Christiansen, Emil [Vis alle 9 forfattere av denne artikkelen] (2023). Osteocyte-Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model. JBMR Plus. s. 1–10. doi: 10.1002/jbm4.10792. Fulltekst i vitenarkiv Vis sammendrag

  In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte-like cells were identified as entrapped, stellate-shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte-like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte-like cell differentiation, cross-talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue-specific biochemical, biophysical, and mechanical properties.

• Printzell, Lisa; Reseland, Janne Elin; Edin, Nina Frederike Jeppesen; Tiainen, Hanna & Ellingsen, Jan Eirik (2023). The dose-dependent impact of γ-radiation reinforced with backscatter from titanium on primary human osteoblasts. Biomaterial Investigations in Dentistry. 10(1). doi: 10.1080/26415275.2023.2209116. Fulltekst i vitenarkiv Vis sammendrag

  In head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts.

• Weber, Florian; Quach, Huy Quang; Reiersen, Mathias; Sarraj, Sadaf Yosef; Bakir, Dyala Nidal Akram & Jankowski, Victor Aleksander [Vis alle 8 forfattere av denne artikkelen] (2022). Characterization of the foreign body response of titanium implants modified with polyphenolic coatings. Journal of Biomedical Materials Research. Part A. ISSN 1549-3296. doi: 10.1002/jbm.a.37377. Fulltekst i vitenarkiv Vis sammendrag

  The foreign body response is dictating the outcome of wound healing around any implanted materials. Patients who suffer from chronic inflammatory diseases and impaired wound healing often face a higher risk for implant failure. Therefore, functional surfaces need to be developed to improve tissue integration. For this purpose, we evaluated the impact of surface coatings made of antioxidant polyphenolic molecules tannic acid (TA) and pyrogallol (PG) on the host response in human blood. Our results showed that although the polyphenolic surface modifications impact the initial blood protein adsorption compared to Ti, the complement and coagulation systems are triggered. Despite complement activation, monocytes and granulocytes remained inactivated, which was manifested in a low pro-inflammatory cytokine expression. Under oxidative stress, both coatings were able to reduce intracellular reactive oxygen species in human gingival fibroblasts (hGFs). However, no anti-inflammatory effects of polyphenolic coatings could be verified in hGFs stimulated with lipopolysaccharide and IL-1β. Although polyphenols reportedly inhibit the NF-κB signaling pathway, phosphorylation of NF-κB p65 was observed. In conclusion, our results indicated that TA and PG coatings improved the hemocompatibility of titanium surfaces and have the potential to reduce oxidative stress during wound healing.

• Fontelo, Raul; Costa, Diana Soares da; Gomez-Florit, Manuel; Tiainen, Hanna; Reis, Rui L. & Novoa-Carballal, Ramon [Vis alle 7 forfattere av denne artikkelen] (2022). Antibacterial nanopatterned coatings for dental implants. Journal of materials chemistry. B. ISSN 2050-750X. doi: 10.1039/d2tb01352e. Fulltekst i vitenarkiv Vis sammendrag

  Dental implants, usually made of titanium, are exposed to hostile oral microflora that facilitate bacterial infections and subsequent inflammation. To mitigate these processes, we coated titanium substrates with block copolymer nanopatterns and investigated the bactericidal effect of these coatings against Gram-positive and Gram-negative bacteria. We found that the bactericidal efficacy of the coatings depends on their morphology and surface chemistry as well as on the bacterial strain: an optimal combination can lead to significant bacterial death for a short time, i.e. 90% for 90 min. Human gingival fibroblasts in contact with the nanopatterned coatings showed similar cell attachment and morphology as on bare Ti. Immunostaining assays showed similar levels of CCR7 and CD206 in macrophages cultured over the nanopatterns and bare Ti, demonstrating adequate properties for tissue integration. The nanopatterns induced a small increase in macrophage aspect ratio, which might indicate early states of M2 polarization, given the absence of CD206.

• Weber, Florian; Figueira, Louise Morais Dornelas; Hafiane, Nora; Zaytseva-Zotova, Daria; Bautista, Alejandro Barrantes & Petersen, Fernanda Cristina [Vis alle 7 forfattere av denne artikkelen] (2022). Can polyphenolic surface modifications prevent fungal colonization of titanium dental implants? Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 219. doi: 10.1016/j.colsurfb.2022.112813. Fulltekst i vitenarkiv Vis sammendrag

  Oral biofilms can be a major health problem causing infections and chronic inflammation of mucosal tissue. While much effort is put in the investigation of bacteria in biofilms, the role of fungi is often neglected, despite Candida albicans playing a key role in the formation of multispecies oral biofilms. With the rise of antibiotic resistance, new strategies to reduce microbial growth need to be found. Therefore, plant derived polyphenolic molecules have been suggested to reduce both adhesion and growth of pathogenic bacteria and fungi. In this study, we investigated the use of polyphenolic coatings to reduce adhesion and biofilm formation of C. albicans BWP17 on titanium implants. Tannic acid and pyrogallol coatings altered the hydrophobic and charge properties of titanium surfaces, and both compounds were gradually released as active molecules over time. Despite such effects, we found no significant inhibition on growth and biofilm formation of C. Albicans, indicating that the release of active molecules from the coatings did not reach relevant inhibitory concentrations. However, a potential antibiofilm effect was observed by the pH-dependent disassembly of the polyphenolic layer, which caused the biofilm to detach. Hence, further efforts are required to create tailored implant surfaces, which sustainably reduce microbial growth and adhesion.

• Chahal, Aman S; Gomez-Florit, Manuel; Domingues, Rui M. A,; Gomes, Manuela E. & Tiainen, Hanna (2021). Human platelet lysate-loaded poly(ethylene glycol) hydrogels induce stem cell chemotaxis in vitro. Biomacromolecules. ISSN 1525-7797. doi: 10.1021/acs.biomac.1c00573. Fulltekst i vitenarkiv Vis sammendrag

  Platelet lysates (PL) contain a selection of proteins and growth factors (GFs) that are known to mediate cell activity. Many of these biomolecules have been identified as chemoattractants with the capacity to induce cell migration. In order to effectively deliver and retain these biomolecules to the site of injury, a scaffold containing PL could be an option. We use poly(ethylene glycol) (PEG) hydrogels consisting of 90 vol % PL to investigate their migratory potential on human mesenchymal stem cells (hMSCs). Cells exposed to these hydrogels were tracked, resulting in cell trajectories and detailed migratory parameters (velocity, Euclidean distance, directness, and forward migration index). Volumetric swelling ratios, hydrogel mechanical properties, and the release kinetics of proteins and GFs from hydrogels were also assessed. Furthermore, hMSC spheroids were encapsulated within the hydrogels to qualitatively assess cell invasion by means of sprouting and disintegration of the spheroid. Cell spheroids encapsulated within the PL-PEG gels exhibited initial outgrowths and eventually colonized the 3D matrix successfully. Results from this study confirmed that hMSCs exhibit directional migration toward the PL-loaded hydrogel with increased velocity and directness, compared to the controls. Overall, the incorporation of PL renders the PEG hydrogel bioactive. This study demonstrates the capacity of PL-loaded hydrogel constructs to attract stem cells for endogenous tissue engineering purposes.

• Vilaça, Adriana; Domingues, Rui M. A,; Tiainen, Hanna; Mendes, Bárbara B.; Bautista, Alejandro Barrantes & Reis, Rui L. [Vis alle 8 forfattere av denne artikkelen] (2021). Multifunctional surfaces for improving soft tissue integration. Advanced Healthcare Materials. ISSN 2192-2640. doi: 10.1002/adhm.202001985. Fulltekst i vitenarkiv Vis sammendrag

  Metallic implants are widely used in diverse clinical applications to aid in recovery from lesions or to replace native hard tissues. However, the lack of integration of metallic surfaces with soft tissue interfaces causes the occurrence of biomaterial‐associated infections, which can trigger a complicated inflammatory response and, ultimately, implant failure. Here, a multifunctional implant surface showing nanoscale anisotropy, based on the controlled deposition of cellulose nanocrystals (CNC), and biological activity derived from platelet lysate (PL) biomolecules sequestered and presented on CNC surface, is proposed. The anisotropic radial nanopatterns are produced on polished titanium surfaces by spin‐coating CNC at high speed. Furthermore, CNC surface chemistry allows to further sequester and form a coating of bioactive molecules derived from PL. The surface anisotropy provided by CNC guides fibroblasts growth and alignment up to 14 days of culture. Moreover, PL‐derived biomolecules polarize macrophages toward the M2‐like anti‐inflammatory phenotype. These results suggest that the developed multifunctional surfaces can promote soft tissue integration to metallic implants and, at the same time, prevent bacterial invasion, tissue inflammation, and failure of biomedical metallic implants.

• Klemm, Anne & Tiainen, Hanna (2021). Highly porous Sr-doped TiO2 ceramics maintain compressive strength after grain boundary corrosion. Journal of the European Ceramic Society. ISSN 0955-2219. doi: 10.1016/j.jeurceramsoc.2021.04.059. Fulltekst i vitenarkiv Vis sammendrag

  Maintaining sufficient mechanical support during bone healing is an essential property for ceramic bone scaffolds. However, grain boundary (GB) dissolution may compromise the mechanical strength of polycrystalline ceramics in the physiological environment. Therefore, we investigated the GB formation and its impact on the compressive strength and corrosion behavior in TiO2 scaffolds doped with calcium and strontium. To alter the GB composition and densification process, sintering conditions were altered. Prolonged sintering times and increased sintering temperature led to improved densification and increased strength in Ca-doped scaffolds. However, dissolution of the resulting amorphous GBs caused a significant loss of compressive strength when exposed to an acidic environment. In contrast, a crystalline SrTiO3 GB phase present in Sr-doped scaffolds, for which increased sintering temperature combined with rapid cooling led to a significantly improved compressive strength. Formation of SrTiO3 crystals in the GBs maintained the strength for over 4 weeks in an acidic environment.

• Thieu, Minh Khai Le; Homayouni, Amin; Hæren, Lena Ringsby; Tiainen, Hanna; Verket, Anders & Ellingsen, Jan Eirik [Vis alle 13 forfattere av denne artikkelen] (2021). Impact of simultaneous placement of implant and block bone graft substitute: an in vivo peri-implant defect model. Biomaterials Research. ISSN 1226-4601. 25(43). doi: 10.1186/s40824-021-00245-3. Fulltekst i vitenarkiv Vis sammendrag

  Background Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations. Methods The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology. Results MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO2 group. Conclusions This study demonstrated less bone formation with the use of TiO2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites.

• Rumian, Lucja; Wolf-Brandstetter, Cornelia; Rößler, Sina; Reczyńska, Katarzyna; Tiainen, Hanna & Haugen, Håvard Jostein [Vis alle 8 forfattere av denne artikkelen] (2020). Sodium alendronate loaded poly(L-lactide-co-glycolide) microparticles immobilized on ceramic scaffolds for local treatment of bone defects. Regenerative Biomaterials. s. 1–10. doi: 10.1093/rb/rbaa012. Fulltekst i vitenarkiv Vis sammendrag

  Bone tissue regeneration in critical-size defects is possible after implantation of a three-dimensional scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing. Sodium alendronate (Aln), a widely used anti-osteoporosis drug, exhibits strong inhibitory effect on bone resorption performed by osteoclasts. Thus we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide (TiO2) scaffolds and poly(L-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with Aln. The MPs were effectively immobilized on the surface of the scaffolds’ pore walls by human recombinant collagen. Drug release from the scaffolds was characterised by initial burst (24 ± 6% of the drug released within first 24 h) followed by a sustained release phase (on average 5 µg of Aln released per day from day 3 to day 18). In vitro tests showed that Aln in concentrations of 5 µg/mL and 2.5 µg/mL was not cytotoxic for MG-63 osteoblast-like cells (viability between 81 ± 6% to 98 ± 3% of control) but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells (PBMCs), as shown by reduced fusion capability and decreased TRAP 5b activity (56 ± 5% reduction in comparison control after 8 days of culture). Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis, reducing osteoclast activity, but not affecting osteoblast functions, which may be beneficial in the treatment of critical-size bone tissue defects.

• Hugo, Jørgen; Koldsland, Odd Carsten; Aass, Anne Merete & Tiainen, Hanna (2020). Development and initial testing of an in vitro model simulating class II furcation defects. Clinical and Experimental Dental Research. doi: 10.1002/cre2.346. Fulltekst i vitenarkiv Vis sammendrag

  Objective To compare surface topography of porcine and human root dentin and to develop a new in vitro model for class II furcation defects. The hypothesis for this study was that porcine mandible blocks can function as a model for class II furcation defects. Background Treatment of mandibular class II furcation defects is unpredictable. There is a need for in vitro models to investigate new treatment methods. Methods A model to investigate the surface topography of porcine and human root dentin was developed and the two tissues compared by SEM imaging and profilometer. A novel method for studying class II furcation defects was then tested. Blocks of porcine mandibles with molar 3 were prepared. Buccal class II furcation defects were created. The furcation area was isolated and bioluminescent Staphylococcus epidermidis Xen43 was used to form a biofilm in the furcation area to test the functionality of the novel furcation model. Results Micromechanical damage caused by debridement on porcine and human root dentin showed similar pattern. No significant difference in the surface morphological parameters was observed between the corresponding porcine and human samples. The model allowed for assessment of the root surface inside the furcation area. While the number of viable bacteria in the furcation following debridement could be quantified, no significant difference between the treatment groups was detected, likely due to bacterial colonization within the periodontal ligament space. Conclusion Porcine and human root dentin show similar surface topography following surface debridement. Porcine mandible blocks can function as a model for class II furcation defects. However, further development and refinement of the novel in vitro model is warranted.

• Chahal, Aman S; Schweikle, Manuel; Lian, Aina-Mari; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2020). Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells. Journal of Tissue Engineering. 11. doi: 10.1177/2041731420926840. Fulltekst i vitenarkiv Vis sammendrag

  Synthetic hydrogel-amorphous calcium phosphate composites are promising candidates to substitute biologically sourced scaffolds for bone repair. While the hydrogel matrix serves as a template for stem cell colonisation, amorphous calcium phosphate s provide mechanical integrity with the potential to stimulate osteogenic differentiation. Here, we utilise composites of poly(ethylene glycol)-based hydrogels and differently stabilised amorphous calcium phosphate to investigate potential effects on attachment and osteogenic differentiation of human mesenchymal stem cells. We found that functionalisation with integrin binding motifs in the form of RGD tripeptide was necessary to allow adhesion of large numbers of cells in spread morphology. Slow dissolution of amorphous calcium phosphate mineral in the scaffolds over at least 21 days was observed, resulting in the release of calcium and zinc ions into the cell culture medium. While we qualitatively observed an increasingly mineralised extracellular matrix along with calcium deposition in the presence of amorphous calcium phosphate-loaded scaffolds, we did not observe significant changes in the expression of selected osteogenic markers.

• Weber, Florian; Sagstuen, Einar; Zhong, Qi-Zhi; Zheng, Tian & Tiainen, Hanna (2020). Tannic Acid Radicals in the Presence of Alkali Metal Salts and Their Impact on the Formation of Silicate-Phenolic Networks. ACS Applied Materials & Interfaces. ISSN 1944-8244. 12(47), s. 52457–52466. doi: 10.1021/acsami.0c16946. Fulltekst i vitenarkiv Vis sammendrag

  Polyphenolic molecules have become attractive building blocks for bioinspired materials due to their adhesive characteristics, capacity to complex ions, redox chemistry, and biocompatibility. For the formation of tannic acid (TA) surface modifications based on silicate-phenolic networks, a high ionic strength is required. In this study, we investigated the effects of NaCl, KCl, and LiCl on the formation of TA coatings and compared it to the coating formation of pyrogallol (PG) using a quartz-crystal microbalance. We found that the substitution of NaCl with KCl inhibited the TA coating formation through the high affinity of K+ to phenolic groups resulting in complexation of TA. Assessment of the radical formation of TA by electron paramagnetic resonance spectroscopy showed that LiCl resulted in hydrolysis of TA forming gallic acid radicals. Further, we found evidence for interactions of LiCl with the Siaq crosslinker. In contrast, the coating formation of PG was only little affected by the substitution of NaCl with LiCl or KCl. Our results demonstrate the interaction potential between alkali metal salts and phenolic compounds and highlight their importance in the continuous deposition of silicate-phenolic networks. These findings can be taken as guidance for future biomedical applications of silicate-phenolic networks involving monovalent ions.

• Weber, Florian; Bautista, Alejandro Barrantes & Tiainen, Hanna (2019). Silicic acid mediated formation of tannic acid nanocoatings. Langmuir. ISSN 0743-7463. 35, s. 3327–3336. doi: 10.1021/acs.langmuir.8b04208. Fulltekst i vitenarkiv Vis sammendrag

  Tannic acid (TA) adheres to a broad variety of different materials and forms versatile surface coatings for technical and biological applications. In mild alkaline conditions, autoxidation processes occur and a firm monolayer is formed. Up to now, thicker coatings are obtained in only a cross-linked multilayer fashion. This study presents an alternative method to form continuous TA coatings using orthosilicic acid (Siaq). Adsorption kinetics and physical properties of TA coatings in the presence of Siaq were determined using a quartz-crystal microbalance and nanoplasmonic spectroscopy. An in situ TA layer thickness of 200 nm was obtained after 24 h in solutions supplemented with 80 μM Siaq. Dry-state measurements indicated a highly hydrated layer in situ. Furthermore, chemical analysis by Fourier transform infrared spectroscopy revealed possible complexation of TA by Siaq, whereas UV–vis spectroscopy did not indicate an interaction of Siaq in the autoxidation process of TA. Investigation of additional metalloid ions showed that germanic acid was also able to initiate a continuous coating formation of TA, whereas boric acid prevented the polymerization process. In comparison to that of TA, the coating formation of pyrogallol (PG) and gallic acid (GA) was not affected by Siaq. PG formed continuous coatings also without Siaq, whereas GA formed only a monolayer in the presence of Siaq. However, Siaq induced a continuous layer formation of ellagic acid. These results indicate the specific importance of orthosilicic acid in the coating formation of polyphenolic molecules with multiple ortho-dihydroxy groups and open new possibilities to deposit TA on interfaces.

• Zhang, Xianbin; Tiainen, Hanna & Haugen, Håvard Jostein (2019). Comparison of titanium dioxide scaffold with commercial bone graft materials through micro-finite element modelling in flow perfusion. Medical and Biological Engineering and Computing. ISSN 0140-0118. 57(1), s. 311–324. doi: 10.1007/s11517-018-1884-2. Fulltekst i vitenarkiv Vis sammendrag

  TiO2 scaffolds have previously shown to have promising osteoconductive properties in previous in vivo experiments. Appropriate mechanical stimuli can further promote this osteoconductive behaviour. However, the complex mechanical environment and the mechanical stimuli enhancing bone regeneration for porous bioceramics have not yet been fully elucidated. This paper aims to compare and evaluate mechanical environment of TiO2 scaffold with three commercial CaP biomaterials, i.e. Bio-Oss, Cerabone and Maxresorb under simulated perfusion culture conditions. The solid phase and fluid phase were modelled as linear elastic material and Newtonian fluid, respectively. The mechanical stimulus was analysed within these porous scaffolds quantitatively. The results showed that the TiO2 had nearly heterogeneous stress distributions, however lower effective Young’s modulus than Cerabone and Maxresorb. The permeability and wall shear stress (WSS) for the TiO2 scaffold was significantly higher than other commercial bone substitute materials. Maxresorb and Bio-Oss showed lowest permeability and local areas of very high WSS. The detailed description of the mechanical performance of these scaffolds could help researchers to predict cell behaviour and to select the most appropriate scaffold for different in vitro and in vivo performances.

• Weber, Florian; Liao, Wei-Chih; Bautista, Alejandro Barrantes; Edèn, Mattias & Tiainen, Hanna (2019). Silicate‐Phenolic Networks: Coordination Mediated Deposition of Bioinspired Tannic Acid Coatings. Chemistry - A European Journal. ISSN 0947-6539. 25(42), s. 9870–9874. doi: 10.1002/chem.201902358. Fulltekst i vitenarkiv Vis sammendrag

  Surface modification with polyphenolic molecules has been pursued in biomedical materials owing to their antioxidant, anti‐inflammatory, and antimicrobial characteristics. Recently, the use of silicic acid (Siaq) as a mediator for efficient surface deposition of tannic acid (TA) was reported, but the postulated Si‐TA polymeric networks were not characterized. Herein, we present unambiguous evidence for silicate‐TA networks that involve Si−O−C motifs by using solid‐state NMR spectroscopy, further supported by XPS and ToF‐SIMS. By using QCM‐D we demonstrate the advantages of Siaq, compared to using transition‐metal ions, to improve the coating efficiency under mildly acidic conditions. The presented homogenous coating buildup and validated applicability in inorganic buffers broadens the use of TA for surface modifications in technological and biomedical applications.

• Klemm, Anne; Gomez-Florit, Manuel; Carvalho, Patricia Almeida; Wachendörfer, Mattis; Gomes, Manuela E. & Haugen, Håvard Jostein [Vis alle 7 forfattere av denne artikkelen] (2019). Grain boundary corrosion in TiO2 bone scaffolds doped with group II cations. Journal of the European Ceramic Society. ISSN 0955-2219. 39, s. 1577–1585. doi: 10.1016/j.jeurceramsoc.2018.12.055. Fulltekst i vitenarkiv Vis sammendrag

  A pH drop during the inflammatory phase during bone regeneration can cause corrosion in TiO2 bone scaffolds and the loss of compressive strength. Corrosion as ion leaching and dissolution is confined to grain boundaries. Cationic doping of TiO2 showed to increase the compressive strength but increased the amount of impurities in grain boundaries as well. Therefore, this study showed the different grain boundary formation for Ca, Sr and Mg doped scaffolds and their corrosion behavior. After corrosion, the amorphous phase in grain boundaries was dissolved in all doped scaffolds. Differences occurred due to the formation of an additional crystalline phase in Sr doped scaffolds. The presence of an amorphous and crystalline phase led to an inhomogeneous dissolution in grain boundaries and a significant decrease in compressive strength already after 4 h in contact with an acidic environment. Released ions did not show any cytotoxic effect on hASCs. Mg doped TiO2 scaffolds led to significant increased osteogenic differentiation.

• Geissler, Sebastian; Gomez-Florit, Manuel; Wiedmer, David; Bautista, Alejandro Barrantes; Petersen, Fernanda Cristina & Tiainen, Hanna (2019). In vitro performance of bioinspired phenolic nanocoatings for endosseous implant applications. ACS Biomaterials Science and Engineering. 5(7), s. 3340–3351. doi: 10.1021/acsbiomaterials.9b00566. Fulltekst i vitenarkiv Vis sammendrag

  In the quest for finding new strategies to enhance tissue integration and to reduce the risk of bacterial colonization around endosseous implants, we report the application of auto-oxidative phenolic coatings made of tannic acid and pyrogallol to titanium surfaces. The functionalized surfaces were screened for their biological performance using cultures of primary human osteoblasts and biofilm-forming bioluminescent staphylococci S. epidermidis Xen43 and S. aureus Xen29. No toxic effect of the coatings on osteoblasts was detected. While tannic acid coatings seemed to induce a delay in osteoblast maturation, they revealed anti-inflammatory potential. Similar effects were observed for pyrogallol coatings deposited for 24 h. Thin pyrogallol coatings deposited for 2 h seemed to promote osteoblast maturation and revealed increased calcium deposition. The effects on osteoblast were found to be related to the release of phenolic compounds from the surfaces. While the phenolic coatings could not inhibit staphylococcal biofilm formation on the titanium surfaces, released phenolic compounds had an inhibitory effect the growth of planktonic bacteria. In conclusion, the assessed coating systems represent a versatile functionalization method which exhibit promising effects for endosseous implant applications.

• Schweikle, Manuel; Bjørnøy, Sindre Hove; Helvoort, Antonius Van; Haugen, Håvard Jostein; Sikorski, Pawel & Tiainen, Hanna (2019). Stabilisation of amorphous calcium phosphate in polyethylene glycol hydrogels. Acta Biomaterialia. ISSN 1742-7061. 90, s. 132–145. doi: 10.1016/j.actbio.2019.03.044. Fulltekst i vitenarkiv Vis sammendrag

  Acellular polymer-calcium phosphate composites are promising bone graft materials. Hydrogels are suitable for providing a temporary matrix, while calcium phosphate minerals serve as ion depots for calcium and phosphate required for de novo bone formation. Crystalline calcium phosphates are stable under biological conditions and are commonly used in such scaffolds. However, the low solubility of these phases reduces the availability of free ions and potentially obstructs the remodelling necessary for the formation of mineralised tissue. Here, we investigate two different strategies to stabilise amorphous calcium phosphates in a synthetic polyethylene glycol-based hydrogel matrix. In vitro experiments mimicking an injectable application showed that amorphous calcium phosphate (ACP) of variable stability was formed in the hydrogel matrices. In additive-free composites, ACP transformed into brushite within minutes. Citrate or zinc additives were found to stabilise the formed ACP phase to different degrees. In the presence of citrate, ACP was stable for at least 2 h before it transformed into hydroxyapatite within 3–20 days. Partial calcium substitution with zinc (Zn/Ca = 10%) produced zinc-doped ACP of high stability that did not show signs of crystallisation for at least 20 days. The presented methods and findings open new possibilities for the design of novel injectable synthetic bone graft materials. The possibility to produce ACP with tailorable stability promises great potential for creating temporary scaffolds with good osteogenic properties. Statement of significance Synthetic hydrogel-calcium phosphate (CaP) composites are promising biomaterials to replace human- and animal-derived bone scaffolds. Most reported hydrogel-CaP composite materials employ crystalline CaP phases that lack the osteoinductive properties of autograft. Stabilising amorphous calcium phosphates (ACP) could overcome this limitation, readily delivering calcium and phosphate ions and facilitating remodelling into new bone tissue. The design of synthetic hydrogel-ACP scaffolds, however, requires more understanding of the mineralisation processes in such matrices. This study presents a model system to characterise the complex mineral formation and transformation processes within a hydrogel matrix. We demonstrate a facile route to produce self-mineralising injectable synthetic hydrogels and prove two different strategies to stabilise ACP for different periods within the formed composites.

• Klemm, Anne & Tiainen, Hanna (2018). Coagulated concentrated anatase slurry leads to improved strength of ceramic TiO⁠2 bone scaffolds. Ceramics International. ISSN 0272-8842. 44(6), s. 6265–6271. doi: 10.1016/j.ceramint.2018.01.013. Fulltekst i vitenarkiv Vis sammendrag

  Slurry behaviour has an important influence on the properties of ceramic scaffolds produced by the polymer sponge method. By adding chloride salts to the TiO2 slurry, the viscosity was increased depending on the chloride concentration at low pH and high particle concentration. Slurries with higher viscosity led to closed and dense scaffold struts combined with high porosity, resulting in a compressive strength over 1.6 MPa. Furthermore, scaffold prepared with 0.1 M CaCl2 and SrCl2 showed the formation of Ca- and Sr-rich phases at the grain boundaries. These ions were also shown to reduce the activation energy for grain growth in the TiO2 scaffold as indicated by the significantly larger grain size. Ca2+-doped scaffolds had the highest compressive strength, while the strength of Sr2+-doped scaffolds was reduced by the formation of a solid solution phase below the sintering temperature.

• Bossard, Cedric; Granel, Henri; Jallot, Édouard; Vial, Christophe; Tiainen, Hanna & Wittrant, Yohann [Vis alle 7 forfattere av denne artikkelen] (2018). Polycaprolactone / bioactive glass hybrid scaffolds for bone regeneration. Biomedical Glasses. ISSN 2299-3932. 4, s. 108–122. doi: 10.1515/bglass-2018-0010. Fulltekst i vitenarkiv Vis sammendrag

  Bioactive glasses (BG) bond to bone and stimulate bone regeneration, but they are brittle. Inorganicorganic hybrids appear as promising bone substitutes since they associate the bone mineral forming ability of BG with the toughness of polymers. Hybrids comprised of polycaprolactone (PCL) and SiO2-CaO BG were produced by sol-gel chemistry and processed into porous scaffolds with controlled pore and interconnection sizes. The obtained scaffolds are highly flexible, meaning that PCL effectively introduces toughness. Apatite formation is observed within 24 hours of immersion in simulated body fluid (SBF) and is not limited to the surface as the entire hybrid progressively changes into bone-like minerals. The degradation rate is suitable for bone regeneration with a 13.2% weight loss after 8 weeks of immersion. Primary osteoblasts cultured in scaffolds demonstrate that the samples are not cytotoxic and provide good cell adhesion. The in vivo study confirms the bioactivity, biocompatibility and suitable degradation rate of the hybrid. A physiological bone made of trabeculae and bone marrow regenerates. The structure and kinetic of bone regeneration was similar to the implanted commercial standard based on bovine bone, demonstrating that this new synthetic PCL-BG hybrid could perform as well as animal-derived bone substitutes.

• Haugen, Sigrid; He, Jianying; Sundaresan, Alamelu; Stunes, Astrid Kamilla; Aasarød, Kristin Matre & Tiainen, Hanna [Vis alle 9 forfattere av denne artikkelen] (2018). Adiponectin reduces bone stiffness; verified in a 3D artificial human bone model in vitro. Frontiers in Endocrinology. 9:236, s. 1–12. doi: 10.3389/fendo.2018.00236. Fulltekst i vitenarkiv Vis sammendrag

  Primary human osteoblasts and osteoclasts incubated in a rotating coculture system without any scaffolding material, form bone-like tissue that may be used to evaluate effects of various compounds on mechanical strength. Circulating adiponectin has been found to be negatively associated with BMD and strength and was therefore assessed in this system. Osteospheres of human osteoblasts and osteoclasts were generated with and without adiponectin. The osteospheres were scanned using micro-computed tomography, the mechanical properties were tested by flat punch compression using nanoindentation equipment, and the cellular morphology characterized by microscopy. The association between autologously produced adiponectin and biomechanical properties was further evaluated by quantitation of adiponectin levels using quantitative polymerase chain reaction (qPCR) and immunoassays, and identification of stiffness by bending test of rat femurs. The molecular mechanisms were examined in vitro using human bone cells. Mechanical testing revealed that adiponectin induced a more compliant osteosphere compared with control. The osteospheres had a round, lobulated appearance with morphologically different areas; inner regions containing few cells embedded in a bone-like material surrounded by an external area with a higher cell quantity. The expression of adiponectin was found to correlate positively to ultimate bending moment and ultimate energy absorption and deflection, on the other hand, it correlated negatively to bending stiffness, indicating autocrine and/or paracrine effects of adiponectin in bone. Adiponectin enhanced proliferation and expression of collagen, leptin, and tumor necrosis factor-alpha in osteoblasts and stimulated proliferation, but not the functional activity of osteoclasts. Our results indicate that both administration of adiponectin during osteosphere production and in situ elevated levels of adiponectin in rat femurs, reduced stiffness of the bone tissues. An increase in undifferentiated cells and extracellular matrix proteins, such as collagen, may explain the reduced bone stiffness seen in the osteospheres treated with adiponectin.

• Chahal, Aman Singh; Schweikle, Manuel; Heyward, Catherine Anne & Tiainen, Hanna (2018). Attachment and spatial organisation of human mesenchymal stem cells on poly(ethylene glycol) hydrogels. Journal of The Mechanical Behavior of Biomedical Materials. ISSN 1751-6161. 84, s. 46–53. doi: 10.1016/j.jmbbm.2018.04.025. Fulltekst i vitenarkiv Vis sammendrag

  Strategies that enable hydrogel substrates to support cell attachment typically incorporate either entire extracellular matrix proteins or synthetic peptide fragments such as the RGD (arginine–glycine–aspartic acid) motif. Previous studies have carefully analysed how material characteristics can affect single cell morphologies. However, the influence of substrate stiffness and ligand presentation on the spatial organisation of human mesenchymal stem cells (hMSCs) have not yet been examined. In this study, we assessed how hMSCs organise themselves on soft (E = 7.4–11.2 kPa) and stiff (E = 27.3–36.8 kPa) poly(ethylene glycol) (PEG) hydrogels with varying concentrations of RGD (0.05–2.5 mM). Our results indicate that hMSCs seeded on soft hydrogels clustered with reduced cell attachment and spreading area, irrespective of RGD concentration and isoform. On stiff hydrogels, in contrast, cells spread with high spatial coverage for RGD concentrations of 0.5 mM or higher. In conclusion, we identified that an interplay of hydrogel stiffness and the availability of cell attachment motifs are important factors in regulating hMSC organisation on PEG hydrogels. Understanding how cells initially interact and colonise the surface of this material is a fundamental prerequisite for the design of controlled platforms for tissue engineering and mechanobiology studies.

• Schweikle, Manuel; Zinn, Thomas; Lund, Reidar & Tiainen, Hanna (2018). Injectable synthetic hydrogel for bone regeneration: Physicochemical characterisation of a high and a low pH gelling system. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 90, s. 67–76. doi: 10.1016/j.msec.2018.04.049. Fulltekst i vitenarkiv Vis sammendrag

  Hybrid poly(ethylene glycol)-co-peptide hydrogels are a versatile platform for bone regeneration. For the use as injectable scaffolds, a good understanding of reaction kinetics and physical properties is vital. However, these factors have not yet been comprehensively illuminated. We show that gelation time can be effectively controlled by pH without affecting the elasticity of the formed hydrogels. Maleimide functionalised PEG gels at lower pH and produces more densely cross-linked networks than vinylsulfone functionalised PEG. Both form non-ideal networks. The elastic moduli on the order of a few kPa are in good agreement with the structural characterisation. Primary human osteoblasts cultured in proximity to bulk gels were not adversely affected in vitro. The results demonstrate that hybrid PEG-peptide hydrogels can be tailored to the requirements of in situ gelation. Attributed to their increased structural properties and a higher tolerance towards low pH, maleimide functionalised hydrogels might provide a better alternative for injectable applications.

• Wiedmer, David; Cui, Chen; Weber, Florian; Petersen, Fernanda Cristina & Tiainen, Hanna (2018). Antibacterial Surface Coating for Bone Scaffolds Based on the Dark Catalytic Effect of Titanium Dioxide. ACS Applied Materials & Interfaces. ISSN 1944-8244. 10(42), s. 35784–35793. doi: 10.1021/acsami.8b12623. Fulltekst i vitenarkiv
• Verket, Anders; Lyngstadaas, Ståle Petter; Tiainen, Hanna; Rønold, Hans Jacob & Wohlfahrt, Johan Caspar (2018). Impact of particulate deproteinized bovine bone mineral and porous titanium granules on early stability and osseointegration of dental implants in narrow marginal circumferential bone defects. International Journal of Oral & Maxillofacial Surgery. ISSN 0901-5027. 47(8), s. 1086–1094. doi: 10.1016/j.ijom.2018.02.007. Fulltekst i vitenarkiv Vis sammendrag

  The use of two particulate bone graft substitute materials in experimental narrow marginal peri-implant bone defects was investigated with respect to early bone healing and implant stability. Porous titanium granules, oxidized white porous titanium granules (WPTG), and demineralized bovine bone mineral (DBBM) were characterized in vitro, after which the two latter materials were tested in experimental peri-implant bone defects in six minipigs, with empty defects as control. After mandibular premolar extraction, the top 5 mm of the alveoli were widened to 6 mm in diameter, followed by the placement of six implants, three on each side, in each pig. Six weeks of healing was allowed. The WPTG showed better mechanical properties. No significant differences in resonance frequency analysis were found directly after compacting or healing, and similar quantities of defect bone formation were observed on micro-computed tomography for all groups. Histomorphometric analysis demonstrated a more coronal bone-to-implant contact in the DBBM group, which also displayed more defect bone fill as compared to the WPTG group. The better mechanical properties observed for WPTG appear of negligible relevance for the early stability and osseointegration of implants.

• Wiedmer, David; Petersen, Fernanda Cristina; Lönn-Stensrud, Jessica & Tiainen, Hanna (2017). Antibacterial effect of hydrogen peroxide - titanium dioxide suspensions in the decontamination of rough titanium surfaces. Biofouling (Print). ISSN 0892-7014. 33(6), s. 451–459. doi: 10.1080/08927014.2017.1322585. Fulltekst i vitenarkiv Vis sammendrag

  The chemical decontamination of infected dental implants is essential for the successful treatment of peri-implantitis. The aim of this study was to assess the antibacterial effect of a hydrogen peroxide-titanium dioxide (H2O2–TiO2) suspension against Staphylococcus epidermidis biofilms. Titanium (Ti) coins were inoculated with a bioluminescent S. epidermidis strain for 8 h and subsequently exposed to H2O2 with and without TiO2 nanoparticles or chlorhexidine (CHX). Bacterial regrowth, bacterial load and viability after decontamination were analyzed by continuous luminescence monitoring, live/dead staining and scanning electron microscopy. Bacterial regrowth was delayed on surfaces treated with H2O2–TiO2 compared to H2O2. H2O2-based treatments resulted in a lower bacterial load compared to CHX. Few viable bacteria were found on surfaces treated with H2O2 and H2O2–TiO2, which contrasted with a uniform layer of dead bacteria for surfaces treated with CHX. H2O2–TiO2 suspensions could therefore be considered an alternative approach in the decontamination of dental implants. © 2017 Taylor & Francis

• Rumian, Lucja; Tiainen, Hanna; Cibor, Urszula; Krok-Borkowicz, Małgorzata; Brzychczy-Włoch, Monika & Haugen, Håvard Jostein [Vis alle 7 forfattere av denne artikkelen] (2017). Ceramic scaffolds with immobilized vancomycin-loaded poly(lactide-co-glycolide) microparticles for bone defects treatment. Materials Letters. ISSN 0167-577X. 190, s. 67–70. doi: 10.1016/j.matlet.2016.12.113. Fulltekst i vitenarkiv
• Müller, Benjamin; Haugen, Håvard Jostein; Nilsen, Ola & Tiainen, Hanna (2016). Atomic layer deposited TiO2 protects porous ceramic foams from grain boundary corrosion. Corrosion Science. ISSN 0010-938X. 106, s. 35–42. doi: 10.1016/j.corsci.2016.01.023. Fulltekst i vitenarkiv Vis sammendrag

  Intergranular corrosion causes a significant loss of compressive strength in highly porous TiO2 foams. In this study, the resistance of conformal atomic layer deposited (ALD) coatings against intergranular corrosion has been investigated. ALD coated TiO2 foams maintained 107% ± 20% and 94% ± 10% of their initial compressive strength for films deposited at 150 °C and 250 °C, respectively. After an immersion period of 28 days in 1 mM HCl, amorphous films showed greater potential in corrosion protection of polycrystalline TiO2 foams. However, anatase coatings with sufficient protection may be more beneficial for cell-material interactions.

• Crica, Livia Elena; Wengenroth, Jonas; Tiainen, Hanna; Ionita, Mariana & Haugen, Håvard Jostein (2016). Enhanced X-ray absorption for micro-CT analysis of low density polymers. Journal of Biomaterials Science. Polymer Edition. ISSN 0920-5063. 27(9), s. 805–823. doi: 10.1080/09205063.2016.1152856. Fulltekst i vitenarkiv Vis sammendrag

  X-ray microtomography (micro-CT), one of the most resourceful instruments for high resolution 3D analysis, can provide qualitative and quantitative accurate structural and compositional information for a broad range of materials. Yet its contribution to the field of biopolymeric materials science is often limited by low imaging contrast due to scarce X-ray attenuation features, particularly for sponges and foam-like structures. This limitation can be overcome to some extent by adjusting the working parameters of micro-CT equipment. However, such approach also facilitates noise and artefacts, and solving the signal-to-noise trade-off has been always problematic. Searching for alternatives turns one’s attention towards the improvement of X-ray attenuation features. While several studies report the use of contrast agents for biological materials, studies to integrate multiple micro-CT approaches for biopolymers were not conducted so far. This method paper is thus aimed to serve as a platform for micro-CT analysis of low X-ray absorptive polymers. Here, several contrast enhancing artifices were developed and trialled on gelatin and poly(vinyl alcohol) biopolymer composites (GP). Accordingly, GP were modified with iodine, barium, silver-based chemicals and hexa(methyl disilazane) by two different methods, i.e. addition of high atomic number chemicals during materials synthesis and post-synthesis staining, respectively. Consequently, cross-sectional scanning electron microscopy was emerged as complementary characterization, aimed to confirm the reproducibility of samples morphological features. The most versatile methods were barium chloride additive incorporation and iodine staining coupled with hexa(methyl disilazane) chemical drying. Both methods significantly improved the X-ray absorbance of our polymeric samples, providing better contrast of micro-CT tomograms.

• Verket, Anders; Müller, Benjamin; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik & Haugen, Håvard Jostein [Vis alle 7 forfattere av denne artikkelen] (2016). TiO2 scaffolds in peri-implant dehiscence defects: an experimental pilot study. Clinical Oral Implants Research. ISSN 0905-7161. 27(10), s. 1200–1206. doi: 10.1111/clr.12725. Fulltekst i vitenarkiv
• Müller, Benjamin; Haugen, Håvard Jostein; Simonsen, Siri Lene & Tiainen, Hanna (2016). Grain boundary corrosion of highly porous ceramic TiO<sub>2</sub> foams is reduced by annealing and quenching. Journal of the European Ceramic Society. ISSN 0955-2219. 36(1), s. 179–188. doi: 10.1016/j.jeurceramsoc.2015.09.014. Fulltekst i vitenarkiv
• Geissler, Sebastian; Tiainen, Hanna & Haugen, Håvard Jostein (2016). Effect of cathodic polarization on coating doxycycline on titanium surfaces. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 63, s. 359–366. doi: 10.1016/j.msec.2016.03.012. Fulltekst i vitenarkiv
• Geissler, Sebastian; Barrantes, Alejandro; Tengvall, Pentti; Messersmith, Phillip B. & Tiainen, Hanna (2016). Deposition kinetics of bioinspired phenolic coatings on titanium surfaces. Langmuir. ISSN 0743-7463. 32, s. 8050–8060. doi: 10.1021/acs.langmuir.6b01959. Fulltekst i vitenarkiv Vis sammendrag

  Polyphenols can form functional coatings on a variety of different materials through auto-oxidative surface polymerization in a manner similar to polydopamine coatings. However, the mechanisms behind the coating deposition are poorly understood. We report the coating deposition kinetics of the polyphenol tannic acid (TA) and the simple phenolic compound pyrogallol (PG) on titanium surfaces. The coating deposition was followed in real time over a period of 24 h using a quartz crystal microbalance with dissipation monitoring (QCM-D). TA coatings revealed a multiphasic layer formation: the deposition of an initial rigid layer was followed by the buildup of an increasingly dissipative layer, before mass adsorption stopped after approximately 5 h of coating time. The PG deposition was biphasic, starting with the adsorption of a nonrigid viscoelastic layer which was followed by layer stiffening upon further mass adsorption. Coating evaluation by ellipsometry and AFM confirmed the deposition kinetics determined by QCM-D and revealed maximum coating thicknesses of approximately 50 and 75 nm for TA and PG, respectively. Chemical characterization of the coatings and polymerized polyphenol particles indicated the involvement of both physical and chemical interactions in the auto-oxidation reactions. © 2016 American Chemical Society

• Rumian, Lucja; Tiainen, Hanna; Cibor, Urszula; Krok, Malgorzata; Brzychczy-Wloch, Monika & Haugen, Håvard Jostein [Vis alle 7 forfattere av denne artikkelen] (2016). Ceramic scaffolds enriched with gentamicin loaded poly(lactide-co-glycolide) microparticles for prevention and treatment of bone tissue infections. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. doi: 10.1016/j.msec.2016.07.065. Fulltekst i vitenarkiv
• Wiedmer, David; Sagstuen, Einar; Welch, Ken; Haugen, Håvard Jostein & Tiainen, Hanna (2016). Oxidative power of aqueous non-irradiated TiO2-H2O2 suspensions: Methylene blue degradation and the role of reactive oxygen species. Applied Catalysis B: Environmental. ISSN 0926-3373. 198, s. 9–15. doi: 10.1016/j.apcatb.2016.05.036. Fulltekst i vitenarkiv Vis sammendrag

  In the present study, the degradation of methylene blue in non-irradiated TiO2-H2O2 suspensions was investigated. Five commercially available catalysts were characterised (BET surface area, zeta potential, hydrodynamic diameter) and their oxidative power was assessed by means of the degradation of methylene blue. A subsequent EPR study was made to verify and identify potential oxidative radicals. The results showed that all suspensions could degrade methylene blue significantly stronger compared to hydrogen peroxide alone. A broad variation between the different catalysts in their capability to adsorb dye molecules was found which was essential for decomposition of methylene blue in darkness. The highest degradation rate of all samples was found for Degussa P25 at neutral pH. EPR studies of this sample verified the presence of oxygen centred radicals namely hydroxyl (radical dotOH) and superoxide radicals (O2−radical dot/radical dotOOH). Non-irradiated TiO2-H2O2 systems show great potential not only in dye removal applications but also in the field of disinfection where low concentrations of hydrogen peroxide are required and irradiation may not be feasible.

• Müller, Benjamin; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2015). Cell growth on pore-graded biomimetic TiO2 bone scaffolds. Journal of Biomaterials Applications. ISSN 0885-3282. 29(9), s. 1284–1295. doi: 10.1177/0885328214559859. Fulltekst i vitenarkiv
• Xing, Rui; Witsø, Ingun Lund; Jugowiec, David; Tiainen, Hanna; Shabestari, Maziar & Lyngstadaas, Ståle Petter [Vis alle 8 forfattere av denne artikkelen] (2015). Antibacterial effect of doxycycline-coated dental abutment surfaces. Biomedical Materials. ISSN 1748-6041. 10(5), s. 55003–55012. doi: 10.1088/1748-6041/10/5/055003. Fulltekst i vitenarkiv Vis sammendrag

  Biofilm formation on dental abutment may lead to peri-implant mucositis and subsequent peri-implantitis. These cases are clinically treated with antibiotics such as doxycycline (Doxy). Here we used an electrochemical method of cathodic polarization to coat Doxy onto the outer surface of a dental abutment material. The Doxy-coated surface showed a burst release in phosphate-buffered saline during the first 24 h. However, a significant amount of Doxy remained on the surface for at least 2 weeks especially on a 5 mA–3 h sample with a higher Doxy amount, suggesting both an initial and a long-term bacteriostatic potential of the coated surface. Surface chemistry was analyzed by x-ray photoelectron spectroscopy and secondary ion mass spectrometry. Surface topography was evaluated by field emission scanning electron microscopy and blue-light profilometry. Longer polarization time from 1 h to 5 h and higher current density from 1 to 15 mA cm−2 resulted in a higher amount of Doxy on the surface. The surface was covered by a layer of Doxy less than 100 nm without significant changes in surface topography. The antibacterial property of the Doxy-coated surface was analyzed by biofilm and planktonic growth assays using Staphylococcus epidermidis. Doxy-coated samples reduced both biofilm accumulation and planktonic growth in broth culture, and also inhibited bacterial growth on agar plates. The antibacterial effect was stronger for samples of 5 mA–3 h coated with a higher amount of Doxy compared to that of 1 mA–1 h. Accordingly, an abutment surface coated with Doxy has potential for preventing bacterial colonization when exposed to the oral cavity. Doxy-coating could be a viable way to control peri-implant mucositis and prevent its progression into peri-implantitis.

• Pullisaar, Helen; Verket, Anders; Szoke, Krisztina; Tiainen, Hanna; Haugen, Håvard Jostein & Brinchmann, Jan E. [Vis alle 8 forfattere av denne artikkelen] (2015). Alginate hydrogel enriched with enamel matrix derivative to target osteogenic cell differentiation in TiO2 scaffolds. Journal of Tissue Engineering. 6. doi: 10.1177/2041731415575870. Fulltekst i vitenarkiv Vis sammendrag

  The purpose of bone tissue engineering is to employ scaffolds, cells, and growth factors to facilitate healing of bone defects. The aim of this study was to assess the viability and osteogenic differentiation of primary human osteoblasts and adipose tissue–derived mesenchymal stem cells from various donors on titanium dioxide (TiO2) scaffolds coated with an alginate hydrogel enriched with enamel matrix derivative. Cells were harvested for quantitative reverse transcription polymerase chain reaction on days 14 and 21, and medium was collected on days 2, 14, and 21 for protein analyses. Neither coating with alginate hydrogel nor alginate hydrogel enriched with enamel matrix derivative induced a cytotoxic response. Enamel matrix derivative–enriched alginate hydrogel significantly increased the expression of osteoblast markers COL1A1, TNFRSF11B, and BGLAP and secretion of osteopontin in human osteoblasts, whereas osteogenic differentiation of human adipose tissue–derived mesenchymal stem cells seemed unaffected by enamel matrix derivative. The alginate hydrogel coating procedure may have potential for local delivery of enamel matrix derivative and other stimulatory factors for use in bone tissue engineering.

• Rumian, Lucja; Reczynska, Katarzyna; Wrona, Małgorzata; Tiainen, Hanna; Haugen, Håvard Jostein & Pamula, Elzbieta (2015). The influence of sintering conditions on microstructure and mechanical properties of titanium dioxide scaffolds for the treatment of bone tissue defects. Acta of Bioengineering and Biomechanics. ISSN 1509-409X. 17(1), s. 3–9. doi: 10.5277/ABB-00129-2014-02. Fulltekst i vitenarkiv Vis sammendrag

  In this study the attempts to improve mechanical properties of highly-porous titanium dioxide scaffolds produced by polymer sponge replication method were investigated. Particularly the effect of two-step sintering at different conditions on microstructure (studied by microcomputed tomography and scanning electron microscopy) and mechanical properties (compression test) of the scaffolds were analysed. Our experiments showed that the most appropriate conditions of manufacturing were when the scaffolds were heat-treated at 1500 oC for 1 h followed by sintering at 1200 oC for 20 h. Such scaffolds exhibited the highest compressive strength which was correlated with the highest linear density and the lowest size of grains. Moreover, grain size distribution was narrower with predominating fraction of fine grains 10-20 µm in size. Smaller grains and higher linear density suggested that in this case densification process prevailed undesirable process of grain coarsening, what finally resulted in improved mechanical properties of the scaffolds.

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• Remartinez, Enrique Oreja; Zaytseva-Zotova, Daria; Pal, Subhajit; Messersmith, Phillip B. & Tiainen, Hanna (2025). Development of a Novel Coating to Modulate Hypoxic Signaling for Enhanced Implant Tissue Regeneration. Fulltekst i vitenarkiv
• Ernø, Inger Thea Myklebust; Zaytseva-Zotova, Daria; Heyward, Catherine Anne & Tiainen, Hanna (2025). Tannic acid and arginine nanocoatings for soft tissue integration of titanium dental implants. Fulltekst i vitenarkiv
• Remartinez, Enrique Oreja; Tiainen, Hanna; Bautista, Alejandro Barrantes & Zaytseva-Zotova, Daria (2024). Tannic acid-protein interaction in coated titanium surfaces. Fulltekst i vitenarkiv
• Remartinez, Enrique Oreja; Tiainen, Hanna; Zaytseva-Zotova, Daria & Bautista, Alejandro Barrantes (2024). Interaction of tannic acid and proteins in titanium surfaces. Fulltekst i vitenarkiv
• Rogala, Agnes; Zaytseva-Zotova, Daria; Baran, Anna; Petersen, Fernanda Cristina & Tiainen, Hanna (2024). Inactivated probiotics on tannic acid nanocoating - enhancing bioactivity for improved bone and soft tissue integration. Fulltekst i vitenarkiv
• Tiainen, Hanna; Galli, Enzo; Dumay, Yann & Bautista, Alejandro Barrantes (2024). Desorption of salivary pellicle and primer adsorption on zirconium dioxide dental ceramics. Fulltekst i vitenarkiv
• Rogala, Agnes; Tiainen, Hanna & Zaytseva-Zotova, Daria (2024). QCM-D-based analysis of cell adhesion: a relationship between QCM-D signal change and focal adhesion kinase activation. Fulltekst i vitenarkiv
• Rogala, Agnieszka; Zaytseva-Zotova, Daria; Bautista, Alejandro Barrantes & Tiainen, Hanna (2023). QCM-D combined with live cell imaging reveals inverse correlation between cell adhesion to tannic acid nanocoatings and serum concentration in medium. Fulltekst i vitenarkiv
• Zaytseva-Zotova, Daria; Singh, Simon; Haideri, Frozan; Elkafas, Nadin Abdelwahab Mohamed Abdou; Bautista, Alejandro Barrantes & Singh, Preet Bano [Vis alle 7 forfattere av denne artikkelen] (2023). Capsaicin-loaded microdroplets for the treatment of burning mouth syndrome. Fulltekst i vitenarkiv
• Remartínez, Enrique Oreja; Tiainen, Hanna; Rogala, Agnieszka; Bautista, Alejandro Barrantes & Zaytseva-Zotova, Daria (2023). Tannic Acid/Polyamino acid Layer-by-Layer coating and their interaction with human cells. Fulltekst i vitenarkiv
• Tiainen, Hanna (2023). Biofunctionalized cellulose membrane for guided tissue regeneration. Fulltekst i vitenarkiv
• Weber, Florian; Sagstuen, Einar & Tiainen, Hanna (2021). Influence of monovalent ions on the coating formation of tannic acid. Fulltekst i vitenarkiv
• Weber, Florian; Bautista, Alejandro Barrantes & Tiainen, Hanna (2021). Antioxidant polyphenolic implant coatings for improved wound healing. Fulltekst i vitenarkiv
• Weber, Florian; Bautista, Alejandro Barrantes & Tiainen, Hanna (2021). Can plant polyphenol inspired surface modifications improve tissue integration of titanium implants? Fulltekst i vitenarkiv
• Weber, Florian; Sagstuen, Einar & Tiainen, Hanna (2020). Chemistry of Silica-Phenolic Networks. Fulltekst i vitenarkiv
• Weber, Florian; Bautista, Alejandro Barrantes & Tiainen, Hanna (2019). Plant polyphenolic inspired anti-inflammatory and anti-bacterial surface modifications for dental implants. Fulltekst i vitenarkiv
• Weber, Florian; Liao, Wei-Chih; Bautista, Alejandro Barrantes; Edèn, Mattias & Tiainen, Hanna (2019). Silicic acid mediated formation of tannic acid coatings. Fulltekst i vitenarkiv
• Tiainen, Hanna; Wiedmer, David & Petersen, Fernanda Cristina (2018). Biofilm formation and planktonic growth of S. epidermidis in the presence of phenolic compounds tannic acid and pyrogallol. Fulltekst i vitenarkiv
• Wiedmer, David; Cui, Chen; Petersen, Fernanda Cristina & Tiainen, Hanna (2018). Antibacterial sol-gel coating for bone scaffolds based on the dark catalytic effect of titanium dioxide. Fulltekst i vitenarkiv
• Klemm, Anne; Haugen, Håvard Jostein & Tiainen, Hanna (2018). Grain boundary corrosion in Sr and Ca doped TiO2 bone scaffold. Fulltekst i vitenarkiv Vis sammendrag

  Porous TiO2 scaffolds as a bone support structure showed high porosity combined with high compressive strength1. Doping ceramic scaffolds with Ca or Sr leads to even higher compressive strength and formation of impurity rich grain boundaries2. Grain boundary dissolution can occur during bone healing, because of a local pH drop3. To improve the corrosion resistance of cationic doped TiO2 scaffolds, the objective of this study was to investigate the corrosion depending on doping concentration to evaluate corrosion mechanisms.

• Schweikle, Manuel; Bjørnøy, Sindre Hove; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Helvoort, Antonius Van & Sikorski, Pawel [Vis alle 7 forfattere av denne artikkelen] (2018). Self-mineralising synthetic injectable hydrogels for bone repair. Fulltekst i vitenarkiv
• Weber, Florian; Tiainen, Hanna & Bautista, Alejandro Barrantes (2018). pH dependent coating formation of tannic acid on titanium surfaces. Fulltekst i vitenarkiv
• Bjørnøy, Sindre Hove; Bassett, David; Schweikle, Manuel; Strand, Berit Løkensgard; Tiainen, Hanna & Ucar, Seniz [Vis alle 8 forfattere av denne artikkelen] (2017). Bioinspired mineralization of hydrogels. Fulltekst i vitenarkiv
• Gomez-Florit, Manuel; Geissler, Sebastian; Wiedmer, David; Petersen, Fernanda Cristina & Tiainen, Hanna (2017). Multifunctional polyphenol nanocoatings for improved tissue integration of dental implants. Fulltekst i vitenarkiv
• Schweikle, Manuel; Bjørnøy, Sindre Hove; Zinn, Thomas; Lund, Reidar; Sikorski, Pawel & Tiainen, Hanna (2017). In situ mineralising injectable hydrogels for bone repair. Fulltekst i vitenarkiv
• Schweikle, Manuel; Zinn, Thomas; Lund, Reidar & Tiainen, Hanna (2017). Injectable hydrogel scaffold for regenerative treatment of peri-implantitis defects. Fulltekst i vitenarkiv
• Schweikle, Manuel; Bjørnøy, Sindre Hove; Zinn, Thomas; Lund, Reidar; Sikorski, Pawel & Tiainen, Hanna (2017). Mineralised injectable hydrogels for bone regeneration. Fulltekst i vitenarkiv
• Weber, Florian; Tiainen, Hanna & Bautista, Alejandro Barrantes (2017). pH dependent coating formation of tannic acid on titanium surfaces. Fulltekst i vitenarkiv
• Geissler, Sebastian; Barrantes, Alejandro; Tengvall, Pentti & Tiainen, Hanna (2016). Coating kinetics of bioinspired phenolic films on titanium surfaces. Fulltekst i vitenarkiv
• Geissler, Sebastian; Barrantes, Alejandro; Tengvall, Pentti & Tiainen, Hanna (2016). Reaction kinetics of bioinspired phenolic coatings on titanium surfaces. Fulltekst i vitenarkiv
• Schweikle, Manuel; Hartvig, Rune; Zinn, Thomas & Tiainen, Hanna (2016). Injectable hydrogel scaffold for bone regeneration: gelation and mechanical properties. Fulltekst i vitenarkiv
• Schweikle, Manuel; Hartvig, Rune Andersen; Zinn, Thomas & Tiainen, Hanna (2016). Tuning gelation kinetics and mechanical properties of a synthetic extracellular matrix substitute. Fulltekst i vitenarkiv
• Tiainen, Hanna; Müller, Benjamin; Campos, Lluis; Ramis, Joana Maria; Nilsen, Ola & Haugen, Håvard Jostein (2016). Atomic layer deposited TiO2 protects highly porous ceramic bone scaffolds from grain boundary corrosion. Fulltekst i vitenarkiv
• Klemm, Anne & Tiainen, Hanna (2016). Investigation of ionic strength on aqueous TiO2 slurries and microstructure of sintered TiO2 bone scaffolds. Fulltekst i vitenarkiv
• Geissler, Sebastian; Gomez-Florit, Manuel; Barrantes, Alejandro & Tiainen, Hanna (2016). Deposition kinetics of bioinspired polyphenol nanocoatings and their effect on osteogenic differentiation on titanium surfaces. Fulltekst i vitenarkiv
• Tiainen, Hanna; Müller, Benjamin; Campos, Lluis; Ramis, Joana Maria; Nilsen, Ola & Haugen, Håvard Jostein (2016). Atomic layer deposited titanium dioxide layer protects highly porous ceramic foams from grain boundary corrosion. Fulltekst i vitenarkiv
• Wiedmer, David; Tiainen, Hanna; Petersen, Fernanda Cristina & Haugen, Håvard Jostein (2016). H2O2-TiO2 as potential treatment for peri-implantitis – an in vitro study. Fulltekst i vitenarkiv
• Wiedmer, David; Tiainen, Hanna; Lönn-Stensrud, Jessica; Petersen, Fernanda Cristina & Haugen, Håvard Jostein (2016). TiO2-H2O2 as decontamination agent - an in vitro study. Fulltekst i vitenarkiv
• Rumian, Lucja; Tiainen, Hanna; Posadowska, Urszula; Brzychczy-Włoch, Monika; Haugen, Håvard Jostein & Pamula, Elzbieta (2015). Ceramic scaffolds containing gentamicin sulphate loaded poly(lactic-co-glycolic acid) microparticles for bone tissue engineering. Fulltekst i vitenarkiv
• Wiedmer, David; Tiainen, Hanna; Sagstuen, Einar & Haugen, Håvard Jostein (2015). TiO2 nanoparticles as antibacterial debridement strategy for permanent infected dental implants. Fulltekst i vitenarkiv
• Geissler, Sebastian; Tiainen, Hanna; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered aggregation of an intrinsically disordered proline-rich peptide. Fulltekst i vitenarkiv
• Tiainen, Hanna; Pieprzak, Kaja & Reczyńska, Katarzyna (2015). Effect of sintering conditions on structural and biological properties of TiO2 bone scaffolds. Fulltekst i vitenarkiv
• Geissler, Sebastian; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Electrochemical immobilization of doxycycline on titanium surfaces. Fulltekst i vitenarkiv
• Wiedmer, David; Recklies, Sandra; Bossard, Cedric; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Antibacterial sol-gel coating for ceramic TiO2 scaffolds for bone regeneration. Fulltekst i vitenarkiv
• Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered aggregation of a structurally disordered polyproline peptide. Fulltekst i vitenarkiv
• Wiig, Elisabeth; Tiainen, Hanna; Lian, Aina-Mari; Mann, Vivek; Sundaresan, Alamelu & Haugen, Håvard Jostein [Vis alle 8 forfattere av denne artikkelen] (2015). Effect of microgravity on bone cells in bioinspired ceramic TiO2 scaffolds. Fulltekst i vitenarkiv
• Chahal, Aman Singh; Schweikle, Manuel; Tiainen, Hanna; Koldsland, Odd Carsten; Reseland, Janne Elin & Haugen, Håvard Jostein (2015). Cell-responsive Biomimetic Extracellular Matrix Material for Bone and Dental Pulp Tissue Regeneration. Fulltekst i vitenarkiv
• Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered self-assembly and aggregation of a structurally disordered proline-rich polypeptide. Fulltekst i vitenarkiv
• Wiedmer, David Julian; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Antibacterial debridement strategy for infected permanent dental implants. Fulltekst i vitenarkiv
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Tiainen, Hanna & Hartvig, Rune (2015). Surface treatment of pseudoelastic nickel-titanium. Fulltekst i vitenarkiv
• Schweikle, Manuel; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Development of poly(lactic-co-glycolic acid)-based nanoparticles as a drug delivery system for bone regeneration implants. Fulltekst i vitenarkiv
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Hartvig, Rune & Tiainen, Hanna (2015). Biomolecular coating of Nickel-titanium Shape memory metals. Fulltekst i vitenarkiv

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