Our publications

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.

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.

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 Ɛ^30/28Si 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 δ¹⁸O_chert 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.

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.

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.

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.

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.

Fluorescence analysis of β-TCP ceramics is often used to describe cells found on said ceramics. However, we found, to our knowledge, so far undescribed artifacts which might sometimes be hard to differentiate from cells due to shape and fluorescence behavior. We tried prolonged ultrasound washing as well as Technovit 9100 fixation to reduce these artifacts. While untreated dowels showed no reduction in artifacts no matter the further treatment, Technovit fixation reduced the artifacts with even further reduction achieved by mechanical cleaning. As a consequence, scientists working with these dowels and likely even other types should try to avoid creating false positive results by considering the existence of these artifacts, checking additional filters for unusual fluorescence and by reducing them by using Technovit fixation when possible.

β-TCP ceramics are versatile bone substitute materials and show many interactions with cells of the monocyte-macrophage-lineage. The possibility of monocytes entering microporous β-TCP ceramics has however not yet been researched. In this study, we used a model approach to investigate whether monocytes might enter β-TCP, providing a possible explanation for the origin of CD68-positive osteoclast-like giant cells found in earlier works.
We used flow chambers to unidirectionally load BC, PRP, or PPP into slice models of either 2 mm or 6 mm β-TCP. Immunofluorescence for CD68 and live/dead staining was performed after the loading process.
Our results show that monocytes were present in a relevant number of PRP and BC slices representing the inside of our 2 mm slice model and also present on the actual inside of our 6 mm model. For PPP, monocytes were not found beyond the surface in either model.
Our results indicate the possibility of a new and so far neglected constituent in β-TCP degradation, perhaps causing the process of ceramic degradation also starting from inside the ceramics as opposed to the current understanding. We also demonstrated flow chambers as a possible new in vitro model for interactions between blood and β-TCP.

The biocompatibility and resorption characteristics of β-tricalcium phosphate (β-TCP, Ca₃(PO₄)₂) have made it a coveted alternative for bone grafts. However, the underlying mechanisms governing the biological interactions between β-tricalcium phosphate and osteoclasts remain elusive. It has been speculated that the composition at grain boundaries might vary and affect β-TCP resorption properties. Atom probe tomography (APT) offers a quantitative approach to assess the composition of the grain boundaries, and thus advance our comprehension of the biological responses within the microstructure and chemical composition at the nanoscale. The precise quantitative analysis of chemical composition remains a notable challenge in atom probe tomography, primarily due to the influence of measurement conditions on compositional accuracy. In this study, we investigated the impact of laser pulse energy on the composition of β-TCP using atom probe tomography, aiming for the most precise Ca:P ratio and consistent results across multiple analyses performed with different sets of analysis conditions and on two different instruments.

Ein dauerhafter Verbleib von Implantaten im Körper kann zu Komplikationen führen. So werden Implantate zur Behandlung von Knochenbrüchen nach erfolgter Heilung oftmals wieder entnommen. Diese Entnahme bedingt eine Zweitoperation, die wiederum Risiken mit sich bringt. Im Gegen­satz zu inerten Implantaten aus Titan oder rost­freiem Stahl degradiert metallisches Magnesium im Körper. Idealerweise stützt das biodegradierbare Magnesium-implantat das betroffene Gewebe bis zur Heilung und baut sich anschliessend ohne Nebenwirkungen ab.
Beim Kontakt mit Körperflüssigkeit setzt eine unbeschichtete, nicht passivierte Magnesium­ober­fläche Wasser­stoffgas frei. Durch eine geeignete Beschichtung lässt sich die anfängliche Gasfrei­setzung und Degradation verzögern.

Objectives
Administration of gadolinium-based contrast agents (GBCA) in magnetic resonance imaging results in the long-term retention of gadolinium (Gd) in tissues and organs, including the bone, and may affect their function and metabolism. This study aims to investigate the effects of Gd and GBCA on the proliferation/survival, differentiation, and function of bone cell lineages.

Materials and Methods
Primary murine osteoblasts (OB) and osteoclast progenitor cells (OPC) isolated from C57BL/6J mice were used to test the effects of Gd³⁺ (12.5–100 μM) and GBCA (100–2000 μM). Cultures were supplemented with the nonionic linear Gd-DTPA-BMA (gadodiamide), ionic linear Gd-DTPA (gadopentetic acid), and macrocyclic Gd-DOTA (gadoteric acid). Cell viability and differentiation were analyzed on days 4–6 of the culture. To assess the resorptive activity of osteoclasts, the cells were grown in OPC cultures and were seeded onto layers of amorphous calcium phosphate with incorporated Gd.

Results
Gd³⁺ did not affect OB viability, but differentiation was reduced dose-dependently up to 72.4% ± 6.2%–73.0% ± 13.2% (average ± SD) at 100 μM Gd³⁺ on days 4–6 of culture as compared with unexposed controls (P < 0.001). Exposure to GBCA had minor effects on OB viability with a dose-dependent reduction up to 23.3% ± 10.2% for Gd-DTPA-BMA at 2000 μM on day 5 (P < 0.001). In contrast, all 3 GBCA caused a dose-dependent reduction of differentiation up to 88.3% ± 5.2% for Gd-DTPA-BMA, 49.8% ± 16.0% for Gd-DTPA, and 23.1% ± 8.7% for Gd-DOTA at 2000 μM on day 5 (P < 0.001). In cultures of OPC, cell viability was not affected by Gd³⁺, whereas differentiation was decreased by 45.3% ± 9.8%–48.5% ± 15.8% at 100 μM Gd³⁺ on days 4–6 (P < 0.05). Exposure of OPC to GBCA resulted in a dose-dependent increase in cell viability of up to 34.1% ± 11.4% at 2000 μM on day 5 of culture (P < 0.001). However, differentiation of OPC cultures was reduced on day 5 by 24.2% ± 9.4% for Gd-DTPA-BMA, 47.1% ± 14.0% for Gd-DTPA, and 38.2% ± 10.0% for Gd-DOTA (P < 0.001). The dissolution of amorphous calcium phosphate by mature osteoclasts was reduced by 36.3% ± 5.3% upon incorporation of 4.3% Gd/Ca wt/wt (P < 0.001).

Conclusions
Gadolinium and GBCA inhibit differentiation and activity of bone cell lineages in vitro. Thus, Gd retention in bone tissue could potentially impair the physiological regulation of bone turnover on a cellular level, leading to pathological changes in bone metabolism.

Human joint prostheses experience wear failure due to the complex interactions between Ultra-High-Molecular-Weight Polyethylene (UHMWPE) and Cobalt-Chromium-Molybdenum (CoCrMo). This study uses the wear classification to investigate the gradual and progressive abrasive wear mechanisms in UHMWPE. Pin-on-disc tests were conducted under simulated in vivo conditions, monitoring wear using Acoustic Emission (AE). Two Machine Learning (ML) frameworks were employed for wear classification: manual feature extraction with ML classifiers and a contrastive learning-based Convolutional Neural Network (CNN) with ML classifiers. The CNN-based feature extraction approach achieved superior classification performance (94% to 96%) compared to manual feature extraction (81% to 89%). The ML techniques enable accurate wear classification, aiding in understanding surface states and early failure detection. Real-time monitoring using AE sensors shows promise for interventions and improving prosthetic joint design.

Bisphosphonates (BP) are anti-resorptive drugs that are widely used to prevent bone loss in osteoporosis. Since inhibition of bone resorption will cause a decrease in bone formation through a process called coupling, it is hypothesized that extended treatment protocols may impair bone healing. In this study, β-tri‑calcium-phosphate (βTCP) ceramics were inserted into critical-size long bone defects in estrogen-deficient mice under BP therapy. The study assessed the benefits of coating the ceramics with Bone Morphogenetic Protein-2 (BMP2) and an engineered BMP2 analogue (L51P) that inactivates BMP antagonists on the healing process, implant resorption, and bone formation.
Female NMRI mice (11–12 weeks of age) were ovariectomized (OVX) or sham operated. Eight weeks later, after the manifestation of ovariectomy-induced osteoporotic bone changes, BP therapy with Alendronate (ALN) was commenced. After another five weeks, a femoral critical-size defect was generated, rigidly fixed, and βTCP-cylinders loaded with 0.25 μg or 2.5 μg BMP2, 2.5 μg L51P, and 0.25 μg BMP2/2.5 μg L51P, respectively, were inserted. Unloaded βTCP-cylinders were used as controls. Femora were collected six and twelve weeks post-implantation.
Histological and micro-computer tomography (MicroCT) evaluation revealed that insertion of cylinders coated with 2.5 μg BMP2 accelerated fracture repair and induced significant bone formation compared to controls (unloaded cylinders or coated with 2.5 μg L51P, 0.25 μg BMP2) already six weeks post-implantation, independent of estrogen-deficiency and BP therapy. The simultaneous administration of BMP2 and L51P (0.25 μg BMP2/2.5 μg L51P) did not promote fracture healing six and twelve weeks post-implantation. Moreover, new bone formation within the critical-size defect was directly linked to the removal of the βTCP-implant in all experimental groups. No evidence was found that long-term therapy with ALN impaired the resorption of the implanted graft. However, osteoclast transcriptom signature was elevated in sham and OVX animals upon treatment with BP, with transcript levels being higher at six weeks than at twelve weeks post-surgery. Furthermore, the transcriptome profile of the developing repair tissue confirmed an accelerated repair process in animals treated with 2.5 μg BMP2 implants. L51P did not increase the bioefficacy of BMP2 in the applied defect model.
The present study provides evidence that continuous administration of BP does not inhibit implant resorption and does not alter the kinetics of the healing process of critical-size long bone defects. Furthermore, the BMP2 variant L51P did not enhance the bioefficacy of BMP2 when applied simultaneously to the femoral critical-size defect in sham and OVX mice.

The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed “osteoimmunology,” which focuses on the connection and interplay between the skeletal system and immune cells. Most studies have focused on the “osteogenic” capacity of various types of bone biomaterials, and much less focus has been placed on immune cells despite being the first cell type in contact with implantable devices. Thus, the amount of literature generated to date on this topic makes it challenging to extract needed information. This review article serves as a guide highlighting advancements made in the field of osteo­immunology emphasizing the role of the osteoimmunomodulatory properties of biomaterials and their impact on osteoinduction. First, the various immune cell types involved in bone biomaterial integration are discussed, including the prominent role of osteal macrophages (OsteoMacs) during bone regeneration. Thereafter, key biomaterial properties, including topography, wettability, surface charge, and adsorption of cytokines, growth factors, ions, and other bioactive molecules, are discussed in terms of their impact on immune responses. These findings highlight and recognize the importance of the immune system and osteo­immunology, leading to a shift in the traditional models used to understand and evaluate biomaterials for bone regeneration.

One of the most widely used materials for bone graft substitution is β‐Tricalcium phosphate (β‐TCP; β-Ca₃(PO₄)₂). β-TCP is typically produced by sintering in air or vacuum. During this process, evaporation of phosphorus (P) species occurs, leading to the formation of a calcium-rich alkaline layer. It was recently shown that the evaporation of P species could be prevented by co-sintering β-TCP with dicalcium phosphate (DCPA; CaHPO₄; mineral name: monetite). The aim of this study was to see how a change of sintering atmosphere could affect the physico-chemical and biological properties of β-TCP. For this purpose, three experimental groups were considered: β‐TCP cylinders sintered in air and subsequently polished to remove the surface layer (control group); the same polished cylinders after subsequent annealing at 500 °C in air to generate a calcium-rich alkaline layer (annealed group); and finally, β‐TCP cylinders sintered in a monetite-rich atmosphere and subsequently polished (monetite group). XPS analysis confirmed that cylinders from the annealed group had a significantly higher Ca/P molar ratio at their surface than that of the control group while this ratio was significantly lower for the cylinders from the monetite group. Sintering β‐TCP in the monetite-rich atmosphere significantly reduced the grain size and increased the density. Changes of surface composition affected the activity of osteoclasts seeded onto the surfaces, since annealed β-TCP cylinders were significantly less resorbed than β-TCP cylinders sintered in the monetite-rich atmosphere. This suggests that an increase of the surface Ca/P molar ratio leads to a decrease of osteoclastic resorption.

Statement of Significance
Minimal changes of surface and bulk (< 1%) composition have major effects on the ability of osteoclasts to resorb β-tricalcium phosphate (β-TCP), one of the most widely used ceramics for bone substitution. The results presented in this study are thus important for the calcium phosphate community because (i) β-TCP may have up to 5% impurities according to ISO and ASTM standards and still be considered to be “pure β-TCP”, (ii) β-TCP surface properties are generally not considered during biocompatibility assessment and (iii) a rationale can be proposed to explain the various inconsistencies reported in the literature on the biological properties of β-TCP.

• Since the middle of the 20th century, total hip arthroplasty has become a very successful treatment for all end-stage diseases of the hip joint. Charnley solved with his low frictional torque arthroplasty the problem of wear and friction with the introduction of a new bearing couple and the reduction of the head size, which set the prerequisite for the further development of stem design.
• This narrative review presents the major developments of regular straight stems in hip arthroplasty. It does not only provide an overview of the history but also assembles the generally scarce documentation available regarding the rationale of developments and illustrates often-unsuspected links.
• Charnley's success is based on successfully solving the issue of fixation of the prosthetic components to the bone, using bone cement made of polymethyl-methacrylate. In the field of cemented anchorage of the stem, two principles showing good long-term revision rates emerged over the years: the force-closed and the shape-closed principles.
• The non-cemented anchorage bases on prosthesis models ensure enough primary stability for osteointegration of the implant to occur. For bone to grow onto the surface, not only sufficient primary stability is required but also a suitable surface structure together with a biocompatible prosthetic material is also necessary.

The aim of this study was to produce a composite of microporous β-TCP filled with alginate-gelatin crosslinked hydrogel, clindamycin and bone morphogenetic protein (BMP-2) to prolong the drug-release behaviour for up to 28 days. The most promising alginate-di-aldehyde(ADA)-gelatin gel for drug release from microcapsules was used to fill microporous β-TCP ceramics under directional flow in a special loading chamber. Dual release of clindamycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21 and 28 by high performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). After release, the microbial efficacy of the clindamycin was checked and the biocompatibility of the composite was tested in cell culture. Clindamycin and the model substance FITC-protein A were released from microcapsules over 28 days. The clindamycin burst release was 43 ± 1%. For the loaded ceramics, a clindamycin release above the minimal inhibitory concentration (MIC) until day 9 and a burst release of 90.56 ± 2.96% were detected. BMP-2 was released from the loaded ceramics in low concentrations over 28 days. The release of active substances from β-TCP and hydrogel have already been extensively studied. Directional flow loading is a special procedure in which the ceramic could act as a stabilizer in the bone and, as a biodegradable system, enables a single-stage surgical procedure. Whether ADA-gelatin gel is suitable for this procedure as a more biodegradable alternative to pure alginate or whether a dual release is possible in this composite has not yet been investigated.

The large variability of biological responses to β-TCP implants reported in the literature could possibly be related to subtle differences in the β-TCP crystal structure. The structure contains one partially occupied site Ca(4). In order to better understand the ordering of this site, 12 pairs of unit cells with different Ca(4) site occupancies were combined in different checkerboard patterns with an average occupancy of 3. Atomistic simulations were conducted to identify the lowest energy configurations. The previously published low energy configuration is not the most stable one when considering a larger supercell. Plotting the 662 simulation outputs by lattice parameters a or c versus relative lattice energy revealed clusters of high density which are composed of configurations with predominant motifs of Ca(4) occupancy. The tools introduced in this study can be applied in future simulation studies to better explain the Ca(4) site occupancy in the β-TCP crystal structure.

Background: There are no generally accepted guidelines for polyethylene (PE) glenoid component cementation techniques. In particular, it is not known whether the backside of a PE glenoid should be fully or partially cemented – or not cemented at all. We hypothesized that cementing techniques would have an impact on cement mantle volume and integrity, as well as biomechanical stability, measured as micromotion under cyclic loading.

Methods: To address our hypothesis, 3 different cementation techniques using a single 2-peg PE glenoid design with polyurethane foam were compared regarding (1) the quality and quantity of the cement mantle and (2) bio­mechanical stability after cyclic loading in vitro. Eight identically cemented glenoids per group were used. Group A underwent cement application only into the peg holes, group B received additional complete cement mantle application on the backside of the glenoid, and group C received the same treatment as group B but with additional standardized drill holes in the surface of the glenoid bone for extra cement interdigitation. All glenoids underwent cyclic edge loading by 10⁵ cycles according to ASTM F2028-14. Before and after loading, cement mantle evaluation was performed by XtremeCT and biomechanical strength and loosening were evaluated by measuring the relative motion of the implants.

Results: The cement mantle at the back of the implant was incomplete in group A as compared with groups B and C, in which the complete PE backside was covered with a homogeneous cement mantle. The cement mantle was thickest in group C, followed by group B (P = .006) and group A (P <.001). We did not detect any breakage of the cement mantle in any of the 3 groups after testing.

Organ-on-chip models, developed using microengineering and microfluidic technologies, aim to recreate physiological-like microenvironments of organs or tissues as a tool to study (patho)physiological processes in vitro. On-chip models of bone are relevant for the study of bone physiology, diseases and regenerative processes. While a few bone-on-a-chip models exist, recapitulating the cellular components of bone, these models do not incorporate the chemical and structural characteristics of bone tissue. Herein, the development of a bone-on-a-chip platform is reported that comprises a 3D structural model of bone. To build the platform, first, a 3D model of bone is produced in a polymer using two-photon polymerization (2PP) from a 3D nano-computed tomography scan of trabecular bone. This 3D model is then coated with a layer of bone mineral-like calcium phosphate. Finally, the 3D bone model is integrated inside a microfluidic device suitable for cell culture. Human mesenchymal stromal cells, cultured inside the platform for up to 21 days, show high viability and extensive production of extracellular matrix, rich in collagen. This biomimetic bone-on-a-chip platform can contribute to a better understanding of the processes related to bone formation and remodeling, which in turn can be used for the development of bone regeneration strategies.

The question whether β‐tricalcium phosphate (β‐TCP) can form a solid solution with β-calcium pyrophosphate (β-CPP) and/or hydroxyapatite (HA) has still not been solved. For this reason, wet-chemically synthesized β-TCP powders with only 20 ppm Sr (among 43 tested elements) and with different HA and β-CPP contents, or in other words Ca/P molar ratios, were used. The graphical relationship between these various Ca/P molar ratios determined by X-ray diffraction and by inductively-coupled plasma mass spectrometry showed no discontinuity, indicating the absence of a solid solution between β‐TCP and β-CPP or HA. Analysis of the β‐TCP lattice parameters as a function of the Ca/P molar ratio revealed a discontinuity at a Ca/P molar ratio of 1.500 and a maximum microstrain. These results indicated that at least two β‐TCP structures co-existed, with variable mixing ratios depending on the Ca/P molar ratio, and with a distinct jump at a Ca/P molar ratio of 1.500.

Any significant in vitro evaluation of cartilage tissue engineering and cartilage repair strategies has to be performed under the harsh conditions encountered in vivo within synovial joints. To this end, we have developed a novel automated physiological robot reactor system (PRRS) that is capable of recapitulating complex physiological motions and load patterns within an environment similar to that found in the human knee. The PRRS consists of a mechanical stimulation unit (MSU) and an automatic sample changer (ASC) within an environment control box in which the humidity, temperature, and gas composition are tightly regulated. The MSU has three linear (orthogonal) axes and one rotational degree of freedom (around the z-axis). The ASC provides space for up to 24 samples, which can be allocated to individual stimulation patterns. Cell-seeded scaffolds and ex vivo tissue culture systems were established to demonstrate the applicability of the PRRS to the investigation of the effect of load and environmental conditions on engineering and maintenance of articular cartilage in vitro. The bioreactor is a flexible system that has the potential to be applied for culturing connective tissues other than cartilage, such as bone and intervertebral disc tissue, even though the mechanical and environmental parameters are very different.

Prediction of primary stability is a major challenge in the surgical planning of dental and orthopedic implants. Computational methods become attractive to estimate primary stability from clinical CT images, but implicit finite element analysis of implant press-fit faces convergence issues due to contact and highly distorted elements. This study aims to develop and validate an explicit finite element method to simulate the insertion and primary stability of a rigid implant in a deformable bone while accounting for damage occurring at the bone-implant interface. Accordingly, a press-fit experiment of a conical implant into predrilled bovine trabecular bone was designed and realized for six samples. A displacement-driven cyclic protocol was used to quantify the reaction force and stiffness of the bone-implant system. Homogenized finite element analyses of the experiments were performed by modeling contact with friction and converting an existing constitutive model with elasto-plasticity and damage of bone tissue to be applicable to an explicit time integration scheme where highly distorted elements get deleted. The computed reaction forces and unloading stiffnesses showed high correlations (R² = 0.95 and R² = 0.94) with the experiment. Friction between bone and implant exhibited a strong influence on both reaction force and stiffness. In conclusion, the developed explicit finite element approach with frictional contact and element deletion accounts properly for bone damage during press-fit and will help optimizing dental or orthopedic implant design towards maximal primary stability.

No abstract available.

Validating phase quantification procedures of powder X-ray diffraction (XRD) data for an implementation in an ISO/IEC 17025 accredited environment has been challenging due to a general lack of suitable certified reference materials. The preparation of highly pure and crystalline reference materials and mixtures thereof may exceed the costs for a profitable and justifiable implementation. This study presents a method for the validation of XRD phase quantifications based on semi-synthetic datasets that reduces the effort for a full method validation drastically. Datasets of nearly pure reference substances are stripped of impurity signals and rescaled to 100% crystallinity, thus eliminating the need for the preparation of ultra-pure and -crystalline materials. The processed datasets are then combined numerically while preserving all sample- and instrument-characteristic features of the peak profile, thereby creating multi-phase diffraction patterns of precisely known composition. The number of compositions and repetitions is only limited by computational power and storage capacity. These datasets can be used as input files for the phase quantification procedure, in which statistical validation parameters such as precision, accuracy, linearity, and limits of detection and quantification can be determined from a statistically sound number of datasets and compositions.

It has been reported in the literature that thermal treatment of calcium phosphate ceramics chemically alters the surface composition by phosphate evaporation. To predict the compositional changes, we have developed a thermodynamic model for the evaporation of phosphorous species from CPP, TCP, HA, and TetCP. In an open atmosphere, the model predicts the formation of a surface layer consisting of a sequence of increasingly phosphate-depleted phases. In a closed system, the atmosphere reaches equilibrium with a single-phase surface layer. To verify our model, we performed a series of experiments which confirmed the predicted formation of phosphate-depleted surface layers. These experiments further demonstrated that controlled supersaturation of the atmosphere led to formation of a phosphate-enriched surface layer as a result of phosphate condensation. In conclusion, our thermodynamic model is capable of predicting the surface modification by phosphate evaporation and condensation of calcium phosphate phases during high-temperature processing in different environments.

Polymer surface grafting is widely used in the field of bone regeneration to increase calcium phosphate (CaP) adhesion, with the intent of improving mechanical properties of CaP-polymer composite cements. Reinforcement can be achieved using multiple combined functional groups and/or complex surface geometries that, however, concurrently influence multiple effects such as wetting, roughness, and interfacial strengthening. This study focused on the influence of a chelating group, namely aspartic acid, on the adsorption of divalent ions such as Ba²⁺ or Ca²⁺ onto poly-l-lactic acid (PLA) films. The films were analyzed using contact angle measurements and X-ray photoelectron spectroscopy. The adsorption of CaP and its interfacial mechanical properties were investigated using functionalized PLA monofilaments whose surface roughness was analyzed using white light interferometry. Mechanical analysis was conducted by performing pull-out tests. The surfaces were analyzed using scanning electron microscopy and energy dispersive X-ray spectroscopy. Using aspartic acid as a chelating group resulted in a 50 % increased adsorption of barium, an almost threefold increase in calcium coverage of the fiber compared to the control group and a twofold increase in interfacial stiffness. No significant increase in interfacial strength was determined, most likely due to the weakness of the CaP matrix, which was partially visible as residues on the monofilaments in the postfracture imaging. This study shows the potential of surfaces functionalized with aspartic acid as a simple alternative to complex polypeptide based functional groups for the adsorption of divalent ions such as calcium on poly-lactic acid in bone regenerating applications.