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PUBLICATIONS

Our publications

Our research primarily focuses on the human musculoskeletal system, with an emphasis on tissue regeneration and implants, alongside other specialized fields. Additionally, we concentrate on the manufacturing, processing, and characterization of materials and surfaces. The results of our research activities are published in internationally recognized scientific journals.

Here, you will find a list of publications involving the RMS Foundation, organized by year of publication.

Publications 2025

Workshop on the Latest Advances in Biomedical Applications of Octacalcium Phosphate

Nicola Döbelin, Osamu Suzuki, Christophe Drouet, Jānis Ločs, Gerard Insley, Philip Procter
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2025; 113:e35500
Abstract
The first workshop on the “latest advances in biomedical applications of octacalcium phosphate (OCP)” was or­ganized as a satellite symposium to the Bioceramics33 conference in Solothurn, Switzerland, in October 2023. The event brought together leading researchers and industry representatives to present and discuss their latest ground­breaking research aimed at developing and com­mer­cial­izing advanced OCP-based bio­materials for bone regen­er­a­tion. The topics presented by the six invited speakers ranged from a fundamental understanding of the OCP crystal chemistry to advanced processing and characterization methods, functionalization, bio­mineralization, and com­mer­cial­ization. With this summary report, we are laying the foundation for a continuation of a series of work­shops on the subject of OCP bio­materials in order to promote the exchange between researchers and industry re­pre­sen­tatives and to drive forward the development and com­mer­cial­ization of new improved synthetic bone substitute materials.
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Publications 2024

Decay experiments and microbial community analysis of water lily leaf biofilms: Sediment effects on leaf preservation potential

Brianne Palmer, Sabina Karačić, Shook Ling Low, Kathrin Janssen, Harald Färber, Moritz Liesegang, Gabriele Bierbaum, Carole T. Gee
PLoS ONE 19(12): e0315656
Abstract
Understanding the intricate dynamics of sediment-mediated microbial interactions and their impact on plant tissue preservation is crucial for unraveling the complexities of leaf decay and preservation processes. To elucidate the earliest stages of leaf preservation, a series of decay experiments was carried out for three months on Nymphaea water lily leaves in aquariums with pond water and one of three distinctly different, sterilized, fine-grained substrates—commercially purchased kaolinite clay or fine sand, or natural pond mud. One aquarium contained only pond water as a control. We use 16S and ITS rRNA gene amplicon sequencing to identify and characterize the complex composition of the bacterial and fungal communities on leaves. Our results reveal that the pond mud substrate produces a unique community composition in the biofilms compared to other substrates. The mud substrate significantly influences microbial communities, as shown by the correlation between high concentrations of minerals in the water and bacterial abundance. Furthermore, more biofilm formers are observed on the leaves exposed to mud after two months, contrasting with declines on other substrates. The mud substrate also enhanced leaf tissue preservation compared to the other sediment types, providing insight into the role of sediment and biofilms in fossilization processes. Notably, leaves on kaolinite clay have the fewest biofilm formers by the end of the experiment. We also identify key biofilm-forming microbes associated with each substrate. The organic-rich mud substrate emerges as a hotspot for biofilm formers, showing that it promotes biofilm formation on leaves and may increase the preservation potential of leaves better than other substrates. The mud’s chemical composition, rich in minerals such as silica, iron, aluminum, and phosphate, may slow or suspend decay and facilitate biomineralization, thus paving the way toward leaf preservation. Our study bridges the information gap between biofilms observed on modern leaves and the mineral encrustation on fossil leaves by analyzing the microbial response in biofilms to substrate types in which fossil leaves are commonly found.
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Publications 2024

Correlation of cross-linking as measured by the trans-vinylene index and in vitro wear of polyethylene from various acetabular liner brands

P. Wahl, R. Heuberger, A. Pascucci, T. Imwinkelried, M. Fürstner, N. Icken, M.Schläppi, R. Pourzal, E. Gautier
Bone Joint Res 2024; 13(11): 682–693
Abstract

Aims
Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands.

Methods
Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test.

Results
A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R2 = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI.

Conclusion
The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE.

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Publications 2024

The reactivity of α-tricalcium phosphate powders is affected by minute amounts of β-calcium pyrophosphate and by the synthesis temperature

Marc Bohner, Fabrizio Bigolin, Isabelle Bohner, Thomas Imwinkelried, Yassine Maazouz, Pascal Michel, Christoph Stähli, Yves Viecelli, Nicola Döbelin
Open Ceramics, Volume 19, September 2024, 100647
Abstract
α-tricalcium phosphate (α-TCP) is the most widespread raw material for hydraulic calcium phosphate cements (CPCs). CPCs are widely used in bone repair due to their injectability, setting ability, and osteoconductivity. This study investigated the reactivity of α-TCP powders, focusing on the impact of minor phase impurities, β-calcium pyrophosphate and hydroxyapatite, and the synthesis temperature. The α-TCP powders were synthesized via a solid-state reaction of calcium carbonate and anhydrous dicalcium phosphate, with varying Ca/P molar ratios (1.4850–1.5075) and synthesis temperatures (1175°C–1350 °C). Powders produced with a Ca/P molar ratio below 1.50 and synthesized at a temperature above the melting point of β-CPP (1296 °C) had a broader size distribution and a two to fourfold lower hydraulic reactivity. Conversely, a higher Ca/P molar ratio improved reactivity. The study underscores the importance of precise control over synthesis parameters to enhance the performance of α-TCP-based CPCs, offering insights for optimizing material design in biomedical applications.
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Publications 2024

Silicon and oxygen isotope fractionation in a silicified carbonate rock

Michael Tatzel, Marcus Oelze, Daniel A. Frick, Tommaso Di Rocco, Moritz Liesegang, Maria Stuff, Michael Wiedenbeck
Chemical Geology, Issue 658, 2024, 122120
Abstract
Silicon isotope fractionation during silicification is poorly understood and impedes our ability to decipher paleoenvironmental conditions from Si isotopes in ancient cherts. To investigate isotope fractionation during silica-for‑carbonate replacement we analyzed the microscale Si and O isotope composition in different silica phases in a silicified zebra dolostone as well as their bulk δ18O and Δ’17O compositions. The subsequent replacement of carbonate layers is mimicked by decreasing δ18O and δ30Si. The textural relationship and magnitude of Si and O isotope fractionation is best explained by near-quantitative silica precipitation in an open system with finite Si. A Rayleigh model for silicification suggests positive Ɛ30/28Si during silicification, conforming with predictions for isotope distribution at chemical equilibrium from ab-initio models. Application of the modelled Ɛ30Si-T relationship yields silicification temperatures of approx. 50 C. To reconcile the δ18Ochert composition with these temperatures, the δ18O of the fluid must have been between − 2.5 and − 4 ‰, compositions for which the quartz phases fall close to the oxygen equilibrium fractionation line in three-isotope space. Diagenetic silica replacement appears to occur in O and Si isotopic equilibrium allowing reconstructions of temperatures of silicification from Si isotopes and derive the δ18O composition of the fluid – a highly desired value needed for accurate reconstructions of the temperature- and δ18O histories of the oceans.
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Publications 2024

Inflammatory tissue response in human soft tissue is caused by a higher particle load near carbon fiber-reinforced PEEK compared to titanium plates

E Fleischhacker, CM Sprecher, S Milz, MM Saller, R Wirz, R Zboray, A Parrilli, J Gleich, G Siebenbürger, W Böcker, B Ockert, T Helfen
Acta Biomaterialia, 2024, online 16.04.2024
Abstract

Titanium as the leading implant material in locked plating is challenged by polymers such as carbon fiber-reinforced polyetheretherketone (CFR-PEEK), which became the focus of interest of researchers and manufacturers in recent years. However, data on human tissue response to these new implant materials are rare.

Osteosynthesis plates and peri–implant soft tissue samples of 16 healed proximal humerus fractures were examined ( n = 8 CFR-PEEK, n = 8 titanium). Soft tissue was analyzed by immunohistochemistry and μCT. The entrapped foreign bodies were further examined for their material composition by FTIR. To gain insight into their origin and formation mechanism, explanted and new plates were evaluated by SEM, EDX, profilometry and HR-CT.

In the peri–implant soft tissue of the CFR-PEEK plates, an inflammatory tissue reaction was detected. Tissues contained foreign bodies, which could be identified as tantalum wires, carbon fiber fragments and PEEK particles. Titanium particles were also found in the peri–implant soft tissue of the titanium plates but showed a less intense surrounding tissue inflammation in immunohistochemistry. The surface of explanted CFR-PEEK plates was rougher and showed exposed and broken carbon fibers as well as pro- truding and deformed tantalum wires, especially in used screw holes, whereas scratches were identified on the titanium plate surfaces.

Particles were present in the peri–implant soft tissue neighboring both implant materials and could be clearly assigned to the plate material. Particles from both plate materials caused detectable tissue inflammation, with more inflammatory cells found in soft tissue over CFR-PEEK plates than over titanium plates.

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Publications 2024

The colourful optical appearance of centric diatom fossil frustules with diagenetic nanocrystalline calcite fill

Moritz Liesegang, Mohamed Ghobara, Sabine Matting, Richard Wirth
Facies 70, 1 (2024)
Abstract
Biophotonic nanostructures rarely withstand fossilization processes occurring after burial over geologic time. Even more distinctive is a change introduced to the optical properties during diagenetic processes resulting in a different optical appearance. Here, we report and explain the optical appearance of centric diatom frustules obtained from ash-bearing carbonatecemented concretions on the Greifswalder Oie island (Pomeranian Bay, Germany, southern Baltic Sea). The ultrastructural and mineralogical analysis of the fossil frustules were carried out using electron microscopy techniques and were correlated to the macroscopic and microscopic optical appearance of the frustules before and after acid etching. The unique optical properties of the fossil diatoms were associated with diagenetic nanocrystalline calcite filling the frustules’ areolae. This fill created the macroscopic pale-yellow colour of many frustules, a microscopic iridescence probably associated with diffraction grating behaviour, and microscopic colour rings. The results highlight the unique permineralization process of diatom frustules and might be an addition to the emerging studies on frustule optics and photonics.
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Publications 2024

Optimization of a tunable process for rapid production of calcium phosphate microparticles using a droplet-based microfluidic platform

Y. Alaoui Selsouli, H. S. Rho, M. Eischen-Loges, V. P. Galván-Chacón, C. Stähli, Y. Viecelli, N. Döbelin, M. Bohner, Z. Tahmasebi Birgani, P. Habibović
Front. Bioeng. Biotechnol. 12:1352184
Abstract
Calcium phosphate (CaP) biomaterials are amongst the most widely used synthetic bone graft substitutes, owing to their chemical similarities to the mineral part of bone matrix and off-the-shelf availability. However, their ability to regenerate bone in critical-sized bone defects has remained inferior to the gold standard autologous bone. Hence, there is a need for methods that can be employed to efficiently produce CaPs with different properties, enabling the screening and consequent fine-tuning of the properties of CaPs towards effective bone regeneration. To this end, we propose the use of droplet microfluidics for rapid production of a variety of CaP microparticles. Particularly, this study aims to optimize the steps of a droplet microfluidic-based production process, including droplet generation, in-droplet CaP synthesis, purification and sintering, in order to obtain a library of CaP microparticles with fine-tuned properties. The results showed that size-controlled, monodisperse water-in-oil microdroplets containing calcium- and phosphate-rich solutions can be produced using a flow-focusing droplet-generator microfluidic chip. We optimized synthesis protocols based on in-droplet mineralization to obtain a range of CaP microparticles without and with inorganic additives. This was achieved by adjusting synthesis parameters, such as precursor concentration, pH value, and aging time, and applying heat treatment. In addition, our results indicated that the synthesis and fabrication parameters of CaPs in this method can alter the microstructure and the degradation behavior of CaPs. Overall, the results highlight the potential of the droplet microfluidic platform for engineering CaP microparticle biomaterials with fine-tuned properties.
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Publications 2024

Density and phase-purity of α-TCP obtained by sintering of nano-crystalline powder

C. Stähli, A.J. Salinas, N. Döbelin, A. Testino, M. Bohner
Ceramics International, Volume 50, Issue 6, 15 March 2024, Pages 8586-8593
Abstract
Dense and polished samples are sometimes used to test the in vitro biological response of biomaterials. However, their production can be challenging, for example for α-tricalcium phosphate (α-TCP), a commonly-used bone graft substitute. In this particular case, the ideal sintering conditions are in a temperature range close to the β-α-TCP phase transition (1125 °C). This phase transition is characterized by a 7 % volume increase which typically leads to the formation of cracks. Additionally, the production of a powder suitable for ceramic processing is difficult because α-TCP can only be produced via a thermal process. The initial aim of this study was to produce dense and polished α-TCP samples using an innovative method to produce nano-crystalline α-TCP. However, after observing the formation of β-TCP phase above the β-α-TCP phase transition (1125 °C), the focus of this study was shifted towards this unexpected phenomenon. Specifically, uniaxially compressed bulk samples were sintered at between 1160 and 1240 °C for different durations up to one week. The resulting density reached up to 95 % and was positively associated with green body density and sintering time, while being initially highest when sintered at the lowest temperature. A transient appearance of up to 6 wt% β-TCP was observed during sintering. The higher the sintering temperature was, the shorter and the smaller this transient appearance was. This behavior was attributed to the intrinsic pressure occurring within the material during sintering and which favoured the denser β-TCP phase.
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Publications 2024

Release kinetics of growth factors loaded into β-TCP ceramics in an in vitro model

M. Waldmann, M. Bohner, A. Baghnavi, B. Riedel, M. Seidenstuecker
Frontiers in Bioengineering and Biotechnology 2024; 12: 1441547
Abstract

Introduction: β-TCP ceramics are bone replacement materials that have recently been tested as a drug delivery system that can potentially be applied to endogenous substances like growth factors found in blood platelets to facilitate positive attributes.

Methods: In this work, we used flow chamber loading to load β-TCP dowels with blood suspensions of platelet-rich plasma (PRP), platelet-poor plasma (PPP), or buffy coat (BC) character. PRP and BC platelet counts were adjusted to the same level by dilution. Concentrations of TGF-β1, PDGF-AB, and IGF-1 from dowel-surrounding culture medium were subsequently determined using ELISA over 5 days. The influence of alginate was additionally tested to modify the release.

Results: Concentrations of TGF-β1 and PDGF-AB increased and conclusively showed a release from platelets in PRP and BC compared to PPP. The alginate coating reduced the PDGF-AB release but did not reduce TGF-β1 and instead even increased TGF-β1 in the BC samples. IGF-1 concentrations were highest in PPP, suggesting circulating levels rather than platelet release as the driving factor. Alginate samples tended to have lower IGF-1 concentrations, but the difference was not shown to be significant.

Discussion: The release of growth factors from different blood suspensions was successfully demonstrated for β-TCP as a drug delivery system with release patterns that correspond to PRP activation after Ca2+-triggered activation. The release pattern was partially modified by alginate coating.

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