RMS Foundation
Bischmattstrasse 12
2544 Bettlach
Switzerland
Phone +41 32 644 2000
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.
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.
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.
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.
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.
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.
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.
The Rietveld refinement software Profex is an open-source and platform-independent solution for the processing of powder X-ray diffraction datasets. It is based on the BGMN refinement kernel and uses a description of the diffractometer configuration to determine the instrument-related peak profile. In this article we present a Profex configuration file for the Chemistry and Mineralogy (CheMin) X-ray diffractometer (XRD), which is on-board the Mars Science Laboratory rover Curiosity. For the past decade, Curiosity has been on a mission on Mars to find out whether the planet was once habitable for microbial life. The CheMin XRD determines the mineralogical phases and abundances of Martian soil and rocks in Gale Crater, Mars. Since its arrival on Mars in 2012, Curiosity has analyzed powdered soil and rock samples with the CheMin instrument and transmitting the raw XRD data acquired back to Earth.
Adaptations of Profex to work seamlessly with CheMin XRD datasets involved creating a new configuration file for the CheMin instrument, as well as adding the Mars Mineral Compendium, a compilation of structural models specifically selected for the analysis of Mars sedimentary soil and rock samples, to Profex. Using example refinements, we demonstrate that this software solution is well suited for quantitative analysis of CheMin XRD datasets.
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.
Evaporation of phosphate species during thermal treatment (> 400 °C) of calcium phosphates leads to the formation of an alkaline layer on their surface. The aim of this study was to evaluate the hypothesis that the biological response of thermally treated calcium phosphates is modified by the presence of such an alkaline layer on their surface. For this purpose, 0.125–0.180 mm α- and β-tricalcium phosphate (TCP) granules were obtained by crushing and size classification, with some being subjected to thermal treatment at 500 °C. The four types of granules (α-TCP, β-TCP, α-TCP-500 °C, and β-TCP-500 °C) were implanted subcutaneously and orthotopically in rats. Sham operations served as control.
Subcutaneously, α-TCP and β-TCP induced significantly more multinucleated giant cells (MNGCs) than calcined granules. Most of the induced MNGCs were TRAP-negative, CD-68 positive and cathepsin K-negative, reflecting a typical indication of a reaction with a foreign body. The vessel density was significantly higher in the α-TCP and β-TCP groups than it was in the α-TCP-500 °C and β-TCP-500 °C groups. In the femur model, β-TCP-500 °C induced significantly more new bone formation than that induced by β-TCP. The granule size was also significantly larger in the β-TCP-500 °C group, making it more resistant to degradation than β-TCP. The MNGC density was higher in the α-TCP and β-TCP groups than in the α-TCP-500 °C and β-TCP-500 °C groups, including cathepsin-positive, CD-68 positive, TRAP-positive and TRAP-negative MNGCs.
In conclusion, this study confirms that the biological response of calcium phosphates was affected by the presence of an alkaline layer on their surface. Thermally-treated α-TCP and β-TCP granules produced significantly fewer MNGCs and were significantly less degraded than non-thermally-treated α-TCP and β-TCP granules. Thermally treating α-TCP and β-TCP granules shifts the reaction from a foreign body reaction towards a physiological reaction by downregulating the number of induced MNGCs and enhancing degradation resistance.
The feasibility to use poly-ether-ether-ketone (PEEK) instead of CoCrMo for femoral condyles of knee prostheses was investigated in this pin-on-disc study. This replacement would hinder the release of the toxic elements Co, Cr and Mo and this possibly at lower production costs. In this preliminary pin-on-disc study, the wear of the pairings PEEK vs. ultra-high-molecular-weight polyethylene (UHMWPE) and PEEK vs. vitamin E containing crosslinked polyethylene (XLPE) was investigated in unidirectional and multidirectional wear tests.
The articulating surfaces of the pins and discs were polished after the wear tests, while most of the initial toolmarks were removed. In addition, there were small scratches on the surfaces. Striations and protuberances were found on some of the UHMWPE samples.
All wear factors were relatively small with less than 1 × 10−6 mm3/Nm. Due to the low wear, the resulting weight loss was highly affected by the soaking of the samples. This was especially the case for the discs due to their larger surface. Thus, the wear of the discs was not used for the comparisons. The wear factors for PEEK pins and XLPE pins were in the range of (0.05 to 0.06) × 10−6 mm3/Nm, both for unidirectional and multidirectional motion. The wear of the UHMWPE pins was with (0.07 ± 0.01) × 10−6 mm3/Nm slightly higher under unidirectional motion and with (0.28 ± 0.03) × 10−6 mm3/Nm four times higher under multidirectional motion.
Thus, PEEK should be considered as an alternative to the CoCrMo alloy in knee prostheses, especially when used in combination with XLPE liners.
β-tricalcium phosphate (β-TCP) is one the most used and potent synthetic bone graft substitute. It is not only osteoconductive, but also osteoinductive. These properties, combined with its cell-mediated resorption, allow full bone defects regeneration. Its clinical outcome is sometimes considered to be “unpredictable”, possibly due to a poor understanding of β-TCP physico-chemical properties: β-TCP crystallographic structure is not fully uncovered; recent results suggest that sintered β-TCP is coated with a Ca-rich alkaline phase; β-TCP apatite-forming ability and osteoinductivity may be enhanced by a hydrothermal treatment; β-TCP grain size and porosity are strongly modified by the presence of minute amounts of β-calcium pyrophosphate or hydroxyapatite impurities. The aim of the present article is to provide a critical, but still rather comprehensive review of the current state of knowledge on β-TCP, with a strong focus on its synthesis and physico-chemical properties, and their link to the in vivo response.
Statement of significance
The present review documents the richness, breadth, and interest of the research devoted to β-tricalcium phosphate (β-TCP). β-TCP is synthetic, osteoconductive, osteoinductive, and its resorption is cell-mediated, thus making it one of the most potent bone graft substitutes. This comprehensive review reveals that there are a number of aspects, such as surface chemistry, crystallography, or stoichiometry deviations, that are still poorly understood. As such, β-TCP is still an exciting scientific playground despite a 50 year long history and > 200 yearly publications.
Protuberances on the surface of ultra-high-molecular-weight polyethylene (UHMWPE) pins were chemically and mechanically investigated in order to better understand the tribology of UHMWPE vs. CoCrMo, which is a typical material pairing for joint replacements.
Pin-on-disc wear tests were performed using pins made of UHMWPE articulating against discs made of a CoCrMo alloy. Wear tests were performed using two different test fluids: a standard test liquid used for hip-simulator tests and a synthetic synovial fluid containing hyaluronic acid, albumin, immunoglobulin G, the phospholipid lecithin and additionally sodium azide to fight bacterial growth.
After the wear tests, the pin surfaces exhibited scratches as well as protuberances with a pitting-like appearance. These protuberances, i.e. elevations protruding from the articulating surface, were 6 ± 3 μm high on the pins lubricated with the standard test liquid and 20 ± 5 μm high under the lubrication with the synthetic synovial fluid. Investigating the protuberances using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) showed that these were composed mainly of UHMWPE, together with amine groups from proteins. To our knowledge, the mechanical properties and namely shear resistance of these protuberances were investigated the first time. The hardness and the elastic modulus of the protuberances were similar to the bulk material, as revealed by nanoindentation. The shear resistance of the protuberances as measured by a nanoscratch test method was comparable or even higher than that of the bulk material.
Several mechanisms proposed to explain the osteoinductive potential of calcium phosphates involve surface mineralization (“bioactivity”) and mention the occurrence of concentration gradients between the inner and the outer part of the implanted material. Determining the evolution of the local chemical environment occurring inside the pores of an implanted bone graft substitute (BGS) is therefore highly relevant. A quantitative and fast method was developed to measure the chemical changes occurring within the pores of β-Tricalcium Phosphate (β-TCP) granules incubated in a simulated body fluid. A factorial design of experiment was used to test the effect of particle size, specific surface area, microporosity, and purity of the β-TCP granules. Large pH, calcium and phosphate concentration changes were observed inside the BGS and lasted for several days. The kinetics and magnitude of these changes (up to 2 pH units) largely depended on the processing and properties of the granules. Interestingly, processing parameters that increased the kinetics and magnitude of the local chemical changes are parameters considered to favor calcium phosphate osteoinduction, suggesting that the model might be useful to predict the osteoinductive potential of BGSs.
Statement of significanceRecent results suggest that in situ mineralization of biomaterials (polymers, ceramics, metals) might be key in their ability to trigger ectopic bone formation. This is the reason why the effect on in situ mineralization of various synthesis parameters of β-tricalcium phosphate granules was studied (size, microporosity, specific surface area, and Ca/P molar ratio). To the best of our knowledge, this is the first article devoted to the chemical changes occurring within the pores of a bone graft substitute. We believe that the manuscript will prove to be highly important in the design and mechanistic understanding of drug-free osteoinductive biomaterials.
Bacterial adhesion and subsequent biofilm formation on biomedical implants and devices are a major cause of their failure. As systemic antibiotic treatment is often ineffective, there is an urgent need for antimicrobial biomaterials and coatings. The term “antimicrobial” can encompass different mechanisms of action (here termed “antimicrobial surface designs”), such as antimicrobial-releasing, contact-killing or non-adhesivity. Biomaterials equipped with antimicrobial surface designs based on different mechanisms of action require different in vitro evaluation methods. Available industrial standard evaluation tests do not address the specific mechanisms of different antimicrobial surface designs and have therefore been modified over the past years, adding to the myriad of methods available in the literature to evaluate antimicrobial surface designs. The aim of this review is to categorize fourteen presently available methods including industrial standard tests for the in vitro evaluation of antimicrobial surface designs according to their suitability with respect to their antimicrobial mechanism of action. There is no single method or industrial test that allows to distinguish antimicrobial designs according to all three mechanisms identified here. However, critical consideration of each method clearly relates the different methods to a specific mechanism of antimicrobial action. It is anticipated that use of the provided table with the fourteen methods will avoid the use of wrong methods for evaluating new antimicrobial designs and therewith facilitate translation of novel antimicrobial biomaterials and coatings to clinical use. The need for more and better updated industrial standard tests is emphasized.
Biomaterials can interact with cells directly, that is, by direct contact of the cells with the material surface, or indirectly, through soluble species that can be released to or uptaken from the surrounding fluids. However, it is difficult to characterise the relevance of this fluid-mediated interaction separately from the topography and composition of the substrate, because they are coupled variables. These fluid-mediated interactions are amplified in the case of highly reactive calcium phosphates (CaPs) such as biomimetic calcium deficient hydroxyapatite (CDHA), particularly in static in vitro cultures. The present work proposes a strategy to decouple the effect of ion exchange from topographical features by adjusting the volume ratio between the cell culture medium and biomaterial (VCM/VB). Increasing this ratio allowed mitigating the drastic ionic exchanges associated to the compositional changes experienced by the material exposed to the cell culture medium. This strategy was validated using rat mesenchymal stem cells (rMSCs) cultured on CDHA and beta-tricalcium phosphate (β-TCP) discs using different VCM/VB ratios. Whereas in the case of β-TCP the cell response was not affected by this ratio, a significant effect on cell adhesion and proliferation was found for the more reactive CDHA. The ionic exchange, produced by CDHA at low VCM/VB, altered cell adhesion due to the reduced number of focal adhesions, caused cell shrinkage and further rMCSs apoptosis. This was mitigated when using a high VCM/VB, which attenuated the changes of calcium and phosphate concentrations in the cell culture medium, resulting in rMSCs spreading and a viability over time. Moreover, rMSCs showed an earlier expression of osteogenic genes on CDHA compared to sintered β-TCP when extracellular calcium fluctuations were reduced.
Fluid mediated interactions play a significant role in the bioactivity of calcium phosphates. Ionic exchange is amplified in the case of biomimetic hydroxyapatite, which makes the in vitro characterisation of cell-material interactions especially challenging. The present work proposes a novel and simple strategy to explore the mechanisms of interaction of biomimetic and sintered calcium phosphates with mesenchymal stem cells. The effects of topography and ion exchange are analysed separately by modifying the volume ratio between cell culture medium and biomaterial. High ionic fluctuations interfered in the maturation of focal adhesions, hampering cell adhesion and leading to increased apoptosis and reduced proliferation rate.
Introduction: Local application of antibiotics provides high concentrations at the site of interest, with minimal systemic toxicity. Carrier materials might help manage dead space. Calcium sulphate (CaSO4) has a dissolution time that only slightly exceeds the usually recommended duration of systemic antibiotic treatments. This in vitro study evaluates compatibility, release kinetics and antibacterial activity of new combinations of antibiotics with CaSO4 as carrier material.
Methods: CaSO4 pellets added with 8% w/w antibiotic powder were exposed once in phosphate-buffered saline (PBS) solution and once in bovine plasma, in an elution experiment run over 6 weeks at 37 °C. Antibiotic elution was examined at various time points. Concentration was measured by liquid chromatography with tandem mass spectrometry. Antimicrobial activity was checked with an agar diffusion test.
Results: Piperacillin-tazobactam, ceftazidime, cefepime, and meropenem showed fast reduction of concentration and activity. Flucloxacillin and cefuroxime remained present in relevant concentrations for 4 weeks. Ciprofloxacin, levofloxacin and clindamycin lasted for 6 weeks, but also at cell toxic concentrations. Ceftriaxone showed a near-constant release with only a small reduction of concentration from 130 to 75 mg/l. Elution profiles from PBS and plasma were comparable.
Conclusion: CaSO4 provides new possibilities in the local treatment of bone and joint infections. Ceftriaxone appears to be of particular interest in combination with CaSO4. Release persists at clinically promising concentrations, and appears to have a depot-like slow release from CaSO4, with only a small reduction in activity and concentration over 6 weeks. To the best of our knowledge, such a particular persistent release never was described before, for any antibiotic in combination with a carrier material for local application.
Background: In elderly patients who have sustained an acetabular fracture involving disruption of the quadrilateral plate (QLP), postoperative loading of the joint beyond the level of partial weight-bearing can result in medial redisplacement of the QLP. The purpose of this biomechanical study was to compare the performances of 4 different fixation constructs intended to prevent medial redisplacement of the QLP.
Methods: Anterior column posterior hemitransverse (ACPHT) fractures with disruption of the QLP were created on synthetic hemipelves (fourth-generation Sawbones models) and subsequently stabilized with (1) a 12-hole plate bridging the QLP (Group 1), (2) the plate with added periarticular screws along the QLP (Group 2), (3) the plate combined with an infrapectineal buttress plate (Group 3), or (4) the plate with the added periarticular screws as well as the buttress plate (Group 4). The point of load application on the acetabulum was defined to be the same as the point of application of maximum vertical hip contact force during normal walking. Loads were applied to simulate either partial weight-bearing (20 cycles, from 35 to 350 N) or inadvertent supraphysiologic loads (linearly increasing loads until the onset of failure, defined as fragment displacement of >3 mm). A universal testing machine was synchronized with a digital image correlation system to optically track redisplacement at the QLP. The level of significance was set at p < 0.05.
Results: During experimental simulation of partial weight-bearing, maximum fracture step openings never exceeded 2 mm. During simulation of inadvertent supraphysiologic load, the median load to failure was higher (p < 0.05) in Group 2 (962 N; range, 798 to 1,000 N) and Group 4 (985 N; range, 887 to 1,000 N) compared with Group 1 (445 N; range, 377 to 583 N) and Group 3 (671 N; range, 447 to 720 N).
Conclusions: All 4 fixation constructs performed in an acceptable manner on testing with simulated partial weight-bearing. Only additional periarticular screws along the QLP increased the fixation strength.
Clinical Relevance: Redisplacement of the QLP resulting in an incongruency of the hip joint has been associated with poor long-term outcomes. Within the constraints of this study, periarticular long screws were superior to infrapectineal buttress plates in preventing medial redisplacement of the QLP.
Objective
The aim of this study was to compare UV light and non-thermal plasma (NTP) treatment regarding the improvement of physical material characteristics and cell reaction on titanium surfaces in vitro after short-term functionalization.
Materials and methods
Moderately rough (Ra 1.8–2.0 μm) sandblasted and acid-etched titanium disks were treated by UV light (0.05 mW/cm2 at λ = 360 nm and 2 mW/cm2 at λ = 250 nm) or by NTP (24 W, -0.5 mbar) of argon or oxygen for 12 min each. Surface structure was investigated by scanning electron microscopy, confocal microscopy and X-ray photoelectron spectroscopy (XPS). Hydrophilicity was assessed by dynamic contact angle measurement. Cell attachment, viability, cell proliferation and cytotoxicity were assessed in vitro using murine osteoblast-like cells.
Results
UV irradiation or NTP treatment of titanium surfaces did not alter the surface structure. XPS analysis revealed a significantly increased oxidation of the surface and a decrease of carbon after the use of either method. NTP and UV light led to a significant better cell attachment of murine osteoblasts; significantly more osteoblasts grew on the treated surfaces at each time point (p < 0.001).
Conclusions
UV light as well as NTP modified the surface of titanium and significantly improved the conditions for murine osteoblast cells in vitro. However, results indicate a slight advantage for NTP of argon and oxygen in a short time interval of surface functionalization compared to UV.
Clinical relevance
UV light and NTP are able to improve surface conditions of dental implants made of titanium.
Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted β-tricalcium phosphate (β-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted β-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of β-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic remnants, bone, soft tissue), and additionally for (ii) the localization of the defect site in the post-implantation microCT dataset. Using the similarity matrix, a 94±1% agreement was found between algorithmic results and the visual assessment of 556,800 pixels. Moreover, the comparison of the segmentation results of the same microCT and histology section further confirmed the validity of the present segmentation algorithm. This new technique could lead to a more common use of microCT in analyzing the complex 3D processes and to a better understanding of the biological processes occurring after the implantation of ceramic bone graft substitutes.
STATEMENT OF SIGNIFICANCE:
Calcium-phosphate scaffolds are being increasingly used to repair critical bone defects. Methods for the accurate characterization of the repair process are still lacking. The present study introduced and validated a novel image-processing technique, using micro-computed tomography (mCT) datasets, to investigate material phases present in biopsies. Specifically, the new method combined mCT datasets from the scaffold before and after implantation to access the characteristic data of the ceramic for more accurate analysis of bone biopsies, and as such to better understand the interactions of the scaffold design and the bone repair process.
Objective
The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days.
Material and methods
Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28 days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA.
Results
The release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2 ± 1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14 days. The burst release here was 61.9 ± 4.3%. The native alginate’s burst release was 54.1 ± 7.8%; that of the sterile alginate 40.5 ± 6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5–2.0 μg/mL against Staphylococcus aureus.
Statement of Significance
Drug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the “granule in hydrogel” composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work.
A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells.
Statement of significanceThe evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS).
Aim
To test in vitro the mechanical resistance, rotational misfit and failure mode of three original implant-abutment connections and to compare them to two connections between non-original abutments connected to one of the original implants.
Material and Methods
Three different implants with small diameters (3.3 mm for Straumann Roxolid, 3.5 mm for Nobel Biocare Replace and Astra Tech Osseospeed TX) were connected with individualized titanium abutments.
Twelve implants from each system were connected to their original abutments (Straumann CARES, Nobel Biocare Procera, Astra Tech Atlantis). Twenty-four Roxolid implants were connected with non-original abutments using CAD/CAM procedures from the other two manufacturers (12 Nobel Biocare Procera and 12 Astra Tech Atlantis). For the critical bending test, a Zwick/Roell 1475 machine and the Xpert Zwick/Roell software were used.
Results
The rotational misfit varied when comparing the different interfaces. The use of non-original grade V titanium abutments on Roxolid implants increased the force needed for deformation. The fracture mode was different with one of the original connections.
Conclusions
Non-original abutments differ in design of the connecting surfaces and material and demonstrate higher rotational misfit. These differences may result in unexpected failure modes.
Background
Finding the right balance between tibial coverage and minimal implant overhang is an important factor in TKA. Another significant cause of failure is component malrotation.
Methods
An average master shape of the proximal tibia at TKA resection level was calculated using fine slice computed tomographies of 117 cadaveric knees. To find out whether alternate implant contours would be necessary depending on the patient's body size, we established five subgroups to compare. CAD-Analysis was performed to simulate the overhang produced after ±4°/±7°/±10° rotation.
Results
A master shape for the tibial resection cut (with a 5° posterior slope, 7mm under lateral joint line) could be determined. Neither left vs. right knee joint, nor male vs. female nor the size subdivision appears to alter the calculated master shape significantly. The optimized shape allowing for ±4° of rotational freedom was found to be the best variant.
Conclusions
Valid methods have been obtained to design a two-dimensional average shape of the tibial plateau. The modifications described in this study might come in useful, when designing future implant designs.
Clinical relevance
An optimized fit at the tibial plateau and lower rates of component malrotation may result in better outcomes after TKA.
Purpose
Fixation of periprosthetic hip fractures with intracortical anchorage might not be feasible in cases with bulky implants and/or poor bone stock.
Methods
Rotational stability of new plate inserts with extracortical anchorage for cerclage fixation was measured and compared to the stability found using a standard technique in a biomechanical setup using a torsion testing machine. In a synthetic PUR bone model, transverse fractures were fixed distally using screws and proximally by wire cerclages attached to the plates using “new” (extracortical anchorage) or “standard” (intracortical anchorage) plate inserts. Time to fracture consolidation and complications were assessed in a consecutive series of 18 patients (18 female; mean age 81 years, range 55–92) with periprosthetic hip fractures (ten type B1, eight type C-Vancouver) treated with the new device between July 2003 and July 2010.
Results
The “new” device showed a higher rotational stability than the “standard” technique (p < 0.001). Fractures showed radiographic consolidation after 14 ± 5 weeks (mean ± SD) postoperatively in patients. Revision surgery was necessary in four patients, unrelated to the new technique.
Conclusion
In periprosthetic hip fractures in which fixation with intracortical anchorage using conventional means might be difficult due to bulky revision stems and/or poor bone stock, the new device may be an addition to the range of existing implants.
Background and purpose
Even small differences in design variables for the femoral stem may influence the outcome of a hip arthroplasty. We performed a risk factor analysis for aseptic loosening of 4 different versions of cemented Müller-type straight stems with special emphasis on design modifications (2 shapes, MSS or SL, and 2 materials, CoNiCrMo (Co) or Ti-6Al-7Nb (Ti)).
Methods
We investigated 828 total hip replacements, which were followed prospectively in our in-house register. All stems were operated in the same setup, using Sulfix-6 bone cement and a second-generation cementing technique. Demographic and design-specific risk factors were analyzed using an adjusted Cox regression model.
Results
The 4 versions showed marked differences in 15-year stem survival with aseptic loosening as the endpoint: 94% (95% CI: 89–99) for MSS Co, 83% (CI: 75–91) for SL Co, 81% (CI: 76–87) for MSS Ti and 63% (CI: 56–71) for SL Ti. Cox regression analysis showed a relative risk (RR) for aseptic loosening of 3 (CI: 2–5) for stems made of Ti and of 2 (CI: 1–2) for the SL design. The RR for aseptic stem loosening increased to 8 (CI: 4–15) when comparing the most and the least successful designs (MSS Co and SL Ti).
Interpretation
Cemented Müller-type straight stems should be MSS-shaped and made of a material with high flexural strength (e.g. cobalt-chrome). The surface finish should be polished (Ra < 0.4 μm). These technical aspects combined with modern cement-ing techniques would improve the survival of Müller-type straight stems. This may be true for all types of cemented stems.
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