Welding PROxAb Shuttles: A Modular Approach for Generating Bispecific Antibodies via Site-Specific Protein-Protein Conjugation.

Targeted protein degradation is an innovative therapeutic strategy to selectively eliminate disease-causing proteins. Exemplified by proteolysis-targeting chimeras (PROTACs), they have shown promise in overcoming drug resistance and targeting previously undruggable proteins. However, PROTACs face challenges, such as low oral bioavailability and limited selectivity. The recently published PROxAb Shuttle technology offers a solution enabling the targeted delivery of PROTACs using antibodies fused with PROTAC-binding domains derived from camelid single-domain antibodies (VHHs). Here, a modular approach to quickly generate PROxAb Shuttles by enzymatically coupling PROTAC-binding VHHs to off-the-shelf antibodies was developed. The resulting conjugates retained their target binding and internalization properties, and incubation with BRD4-targeting PROTACs resulted in formation of defined PROxAb-PROTAC complexes. These complexes selectively induced degradation of the BRD4 protein, resulting in cytotoxicity specifically to cells expressing the antibody's target. The chemoenzymatic approach described herein provides a versatile and efficient solution for generating antibody-VHH conjugates for targeted protein degradation applications, but it could also be used to combine antibodies and VHH binders to generate bispecific antibodies for further applications.

Primary bone graft stability after Latarjet surgery: biomechanical evaluation of a fixation technique with metal-free all-suture cerclage vs. cortical screws.

BACKGROUND: To reduce hardware-related complications in coracoid graft fixation to the anterior aspect of the glenoid, a metal-free Latarjet technique was recently introduced. The aim of this study was to compare the primary stability of a classic Latarjet procedure with 2 metal screws to a novel metal-free, all-suture cerclage method. It is hypothesized that fixation of the coracoid graft with 2 malleolar screws will provide higher primary stability compared with an all-suture cerclage technique. METHODS: This biomechanical in vitro study was conducted on 12 fresh-frozen cadaveric shoulders (6 matched pairs) with a mean donor age of 80 years (range, 67-89 years). Coracoid graft fixation was performed using a recently introduced all-suture cerclage technique (group A) or a classic Latarjet technique with two 4.5-mm malleolar screws (group B). The conjoint tendon was loaded with a static force of 10 N to simulate the sling effect. Graft loading with a probe head consisted of 6 ascending load levels (10-50 N, 10-100 N, 10-150 N, 10-200 N, 10-250 N, and 10-300 N) with 100 cycles each at 1 Hz. Relative motion of the bone graft to the glenoid was measured using an optic 3-dimensional system. RESULTS: While loading the conjoint tendon with 10 N, no difference in mean displacement of the bone-graft was found between both groups (P = .144). During cyclic loading, a significant difference in relative displacement for both groups was already detected in load level 1 (group A: 2398.8 µm vs. group B: 125.7 µm; P = .024), and this trend continued with the following load levels (P < .05). DISCUSSION AND CONCLUSION: The study demonstrated that the innovative metal-free, all-suture cerclage fixation technique results in higher micromotion than the classic coracoid graft fixation with 2 malleolar screws. According to the present biomechanical investigation, shoulders treated with a metal-free all-suture cerclage technique might need adapted rehabilitation protocols to protect the construct and allow for graft healing.

Generation and Characterization of Iduronidase-Cleavable ADCs.

A crucial design feature for the therapeutic success of antibody-drug conjugates (ADCs) is the linker that connects the antibody with the drug. Linkers must be stable in circulation and efficiently release the drug inside the target cell, thereby having a fundamental impact on ADC pharmacokinetics and efficacy. The variety of enzymatically cleavable linkers applied in ADCs is limited, and some are believed to be associated with unwanted side effects due to the expression of cleavage-mediating enzymes in nonmalignant cells. Based on a bioinformatic screen of lysosomal enzymes, we identified α-l-iduronidase (IduA) as an interesting candidate for ADC linker cleavage because of its low expression in normal tissues and its overexpression in several tumor types. In the present study, we report a novel IduA-cleavable ADC linker using exatecan and duocarmycin as payloads. We showed the functionality of our linker system in cleavage assays using recombinant IduA or cell lysates and compared it to established ADC linkers. Subsequently, we coupled iduronide-exatecan via interchain cysteines or iduronide-duocarmycin via microbial transglutaminase (mTG) to an anti-CEACAM5 (aCEA5) antibody. The generated iduronide-exatecan ADC showed high serum stability and similar target-dependent tumor cell killing in the subnanomolar range but reduced toxicity on nonmalignant cells compared to an analogous cathepsin B-activatable valine-citrulline-exatecan ADC. Finally, in vivo antitumor activity could be demonstrated for an IduA-cleavable duocarmycin ADC. The presented results emphasize the potential of iduronide linkers for ADC development and represent a tool for further balancing out tumor selectivity and safety.

Soft-tissue fixation is not inferior to suture-anchor fixation in reconstruction of the medial patellofemoral ligament using a nonresorbable suture tape.

PURPOSE: Reconstruction of the medial patellofemoral ligament (MPFL-R) with nonresorbable suture tape (FiberTape®, FT) is becoming popular. Patella-side fixation of the FT can be performed with suture anchors or via soft-tissue fixation. The aim of this study was to investigate whether patella-side soft-tissue fixation can achieve equivalent primary stability compared to suture-anchor fixation. METHODS: In ten human, fresh-frozen knee joint specimens (m/f 6/4; age 74 ± 9 a), the MPFL was identified and dissected near the femoral insertion site. In five knee joints, the MPFL-R using FT was performed with soft-tissue fixation at the patella (study group; SG), and in five knee joints, the FT was fixed via suture anchors (control group, CG). All reconstructions were evaluated until load to failure of the patella-side fixation with a displacement rate of 200 mm/min. RESULTS: The mean maximum load to failure in the SG was 395.3 ± 57.9 N. All reconstructions failed by complete tearing off the medial patellar retinaculum from its medial patellar margin, but fixation of the FT remained stable. In the CG, the mean maximum load to failure was 239.4 ± 54.5 N and was significantly different compared to the SG (p = 0.04). All reconstructions failed via pullout of the suture anchors. Stiffness and elongation did not differ between the groups, and no failure of the FT was observed in any of the specimens. CONCLUSION: Primary stability of soft-tissue MPFL-R using FT was superior to suture-anchor fixation. Both fixation techniques provided sufficient primary stability, superior to previously reported native MPFL tensile strengths. MPFL-R with FT could be a possible alternative procedure for MPFL-R, eliminating potential complications due to autologous tendon graft harvesting.

EGFR binding Fc domain-drug conjugates: stable and highly potent cytotoxic molecules mediate selective cell killing.

The exposition of cancer cells to cytotoxic doses of payload is fundamental for the therapeutic efficacy of antibody drug conjugates (ADCs) in solid cancers. To maximize payload exposure, tissue penetration can be increased by utilizing smaller-sized drug conjugates which distribute deeper into the tumor. Our group recently explored small human epidermal growth factor receptor 2 (HER2) targeting Fc antigen binding fragments (Fcabs) for ADC applications in a feasibility study. Here, we expand this concept using epidermal growth factor receptor (EGFR) targeting Fcabs for the generation of site-specific auristatin-based drug conjugates. In contrast to HER2-targeting Fcabs, we identified novel conjugation sites in the EGFR-targeting Fcab scaffold that allowed for higher DAR enzymatic conjugation. We demonstrate feasibility of resultant EGFR-targeting Fcab-drug conjugates that retain binding to half-life prolonging neonatal Fc receptor (FcRn) and EGFR and show high serum stability as well as target receptor mediated cell killing at sub-nanomolar concentrations. Our results emphasize the applicability of the Fcab format for the generation of drug conjugates designed for increased penetration of solid tumors and potential FcRn-driven antibody-like pharmacokinetics.

Generation and Biological Evaluation of Fc Antigen Binding Fragment-Drug Conjugates as a Novel Antibody-Based Format for Targeted Drug Delivery.

Fragment crystallizable (Fc) antigen binding fragments (Fcabs) represent a novel antibody format comprising a homodimeric Fc region with an engineered antigen binding site. In contrast to their full-length antibody offspring, Fcabs combine Fc-domain-mediated and antigen binding functions at only one-third of the size. Their reduced size is accompanied by elevated tissue penetration capabilities, which is an attractive feature for the treatment of solid tumors. In the present study, we explored for the first time Fcabs as a novel scaffold for antibody-drug conjugates (ADCs). As model, various HER2-targeting Fcab variants coupled to a pH-sensitive dye were used in internalization experiments. A selective binding on HER2-expressing tumor cells and receptor-mediated endocytosis could be confirmed for selected variants, indicating that these Fcabs meet the basic prerequisite for an ADC approach. Subsequently, Fcabs were site-specifically coupled to cytotoxic monomethyl auristatin E yielding homogeneous conjugates. The conjugates retained HER2 and FcRn binding behavior of the parent Fcabs, showed a selective in vitro cell killing and conjugation site-dependent serum stability. Moreover, Fcab conjugates showed elevated penetration in a spheroid model, compared to their full-length antibody and Trastuzumab counterparts. Altogether, the presented results emphasize the potential of Fcabs as a novel scaffold for targeted drug delivery in solid cancers and pave the way for future in vivo translation.

[Tribology in hip arthroplasty : Benefits of different materials]. / Tribologie in der Hüftendoprothetik : Welches Material hat welchen Nutzen?

When it comes to total hip replacements, choosing the suitable material combination is of clinical relevance. The present review article examines the technical differences in wear and corrosion of the relevant material combinations of ceramics, metals, ceramized metals and various types of polyethylene. The material characteristics, which were often tested under standardized conditions in the laboratory, are compared with clinical results on the basis of evidence-graded clinical studies and on the basis of register studies. This article thus represents an up-to-date snapshot of the expectations and actual clinical outcomes of the present choice of material combinations. It shows that some tendencies from the field of materials research, e.g. with regard to cross-linked polyethylene, coincide with observations from practical clinical experience, while for other materials, a proven technical superiority has not yet been confirmed as an evident advantage in clinical practice.

4,5-Diazafluorene N-glycopyranosyl hydrazones as scaffolds for potential bioactive metallo-organic compounds: Synthesis, structural study and cytotoxic activity.

A series of novel N1-(4,5-diazafluoren-9-yliden)-N2-glycopyranosyl hydrazines was prepared in synthetically useful yields by treatment of 9H-4,5-diazafluoren-9-hydrazone with different unprotected monosaccharides. The reactions with the monosaccharides tested afforded stereoselectively, and exclusively, cyclic derivatives, whose structures correspond to N-ß-glycopyranosyl hydrazones except for the d-arabinose derivative that agrees with the α-anomer. Several copper(II) complexes having a 2:1 ligand to metal mole ratio were also prepared. The metal complexes can bind DNA sequences and preferentially stabilize G-quadruplex DNA structures over dsDNA. The fucose, rhamnose and deoxyglucose copper(II) complexes exhibited a cytotoxic activity against cultured HeLa and PC3 tumor cells comparable to other metal complexes normally used for chemotherapeutic purposes, such as cisplatin.

Feasibility and Diagnostic Value of Cardiovascular Magnetic Resonance Imaging After Acute Ischemic Stroke of Undetermined Origin.

BACKGROUND AND PURPOSE: Etiology of acute ischemic stroke remains undetermined (cryptogenic) in about 25% of patients after state-of-the-art diagnostic work-up. METHODS: One-hundred and three patients with magnetic resonance imaging (MRI)-proven acute ischemic stroke of undetermined origin were prospectively enrolled and underwent 3-T cardiac MRI and magnetic resonance angiography of the aortic arch in addition to state-of-the-art diagnostic work-up, including transesophageal echocardiography (TEE). We analyzed the feasibility, diagnostic accuracy, and added value of cardiovascular MRI (cvMRI) compared with TEE for detecting sources of stroke. RESULTS: Overall, 102 (99.0%) ischemic stroke patients (median 63 years [interquartile range, 53-72], 24% female, median NIHSS (National Institutes of Health Stroke Scale) score on admission 2 [interquartile range, 1-4]) underwent cvMRI and TEE in hospital; 89 (86.4%) patients completed the cvMRI examination. In 93 cryptogenic stroke patients, a high-risk embolic source was found in 9 (8.7%) patients by cvMRI and in 11 (11.8%) patients by echocardiography, respectively. cvMRI and echocardiography findings were consistent in 80 (86.0%) patients, resulting in a degree of agreement of κ=0.24. In 82 patients with cryptogenic stroke according to routine work-up, including TEE, cvMRI identified stroke etiology in additional 5 (6.1%) patients. Late gadolinium enhancement consistent with previous myocardial infarction was found in 13 (14.6%) out of 89 stroke patients completing cvMRI. Only 2 of these 13 patients had known coronary artery disease. CONCLUSIONS: Our study demonstrated that cvMRI was feasible in the vast majority of included patients with acute ischemic stroke. The diagnostic information of cvMRI seems to be complementary to TEE but is not replacing echocardiography after acute ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01917955.

Tuning the Lewis acid phenol ortho-prenylation as a molecular diversity tool.

A diversity-oriented approach for the synthesis of various structurally different prenylated alcohols from readily accessible and common precursors was developed. With varying approaches, this article describes some successful examples of a Friedel-Crafts alkylation using methoxyphenols and different prenyl alcohols (geraniol and (E,E)-farnesol). We demonstrated that just by varying the stoichiometry of the Lewis acid used, the course of the reaction can be shifted to produce the alkylated or the cyclized product. Eighteen unique products were obtained with good isolated yields by direct alkylation with or without a consecutive π-cationic cyclization.

Coupling single quantum dots to plasmonic nanocones: optical properties.

Coupling a single quantum emitter, such as a fluorescent molecule or a quantum dot (QD), to a plasmonic nanostructure is an important issue in nano-optics and nano-spectroscopy, relevant for a wide range of applications, including tip-enhanced near-field optical microscopy, plasmon enhanced molecular sensing and spectroscopy, and nanophotonic amplifiers or nanolasers, to mention only a few. While the field enhancement of a sharp nanoantenna increasing the excitation rate of a very closely positioned single molecule or QD has been well investigated, the detailed physical mechanisms involved in the emission of a photon from such a system are, by far, less investigated. In one of our ongoing research projects, we try to address these issues by constructing and spectroscopically analysing geometrically simple hybrid heterostructures consisting of sharp gold cones with single quantum dots attached to the very tip apex. An important goal of this work is to tune the longitudinal plasmon resonance by adjusting the cones' geometry to the emission maximum of the core-shell CdSe/ZnS QDs at nominally 650 nm. Luminescence spectra of the bare cones, pure QDs and hybrid systems were distinguished successfully. In the next steps we will further investigate, experimentally and theoretically, the optical properties of the coupled systems in more detail, such as the fluorescence spectra, blinking statistics, and the current results on the fluorescence lifetimes, and compare them with uncoupled QDs to obtain a clearer picture of the radiative and non-radiative processes.

Au nanotip as luminescent near-field probe.

We introduce a new optical near-field mapping method, namely utilizing the plasmon-mediated luminescence from the apex of a sharp gold nanotip. The tip acts as a quasi-point light source which does not suffer from bleaching and gives a spatial resolution of ≤25 nm. We demonstrate our method by imaging the near field of azimuthally and radially polarized plasmonic modes of nonluminescent aluminum oligomers.

Capsule elongation occurs after first time shoulder dislocation A biomechanical in-vitro investigation on human cadaveric specimen.

Purpose: As capsule elongation is assumed to weaken the static stability of the shoulder joint, the purpose of this biomechanical study was to demonstrate that capsule elongation occurs immediately after a first-time shoulder dislocation and not just after recurrent dislocation events. We hypothesize an increment in joint clearance due to joint capsule elongation after a first-time dislocation. Methods: An experimental in-vitro study was conducted on 6 paired fresh frozen human shoulders (4 females; 2 males; 12 specimen) with a mean age of 80 (Range 67-89) years. The shoulder joint with the articular capsule was exposed and an inferior static tension force of 2.5 N was applied to the humerus prior to dislocation. Next, the humeral head was dislocated and was then immediately reduced back into the start position. The joint gap as well as joint capsule deformation was assessed using optical techniques. Results: The radiographic joint gap increased from 13.7 ± 6.9 mm (prior to dislocation) to 18.1 ± 6.5 mm (post dislocation) (p < .001). The increase in joint clearance was 4.4 mm. The joint capsule elongated from 5.9 ± 0.005 % (prior to dislocation) to 9.4 ± 0.007 % (post dislocation) (p < .001). The mean increase in joint capsule elongation was 3.5 %. Conclusions: Capsule elongation was observed immediately after a simulated first-time shoulder dislocation in an in-vitro model of elderly human cadavers. It might therefore not only be a phenomenon of recurrent dislocation events.

What is the upper limit of cement penetration for different femoral hip resurfacing components?

We used a validated femoral resurfacing model to obtain measurements of pressure and temperature and quantify cement distribution as a function of inner geometry and cementing technique of five different femoral hip resurfacing components. The purpose was to investigate if manufacture cementing recommendations are reliable. ASR showed only with the recommended manual cementing technique low cement pressures of 58.0±50.2kPa and low interface temperatures of 33.3±4.1°C. BHR had large cement defects of 10.4±1.1mm. Conserve Plus caused the smallest cement penetration depths of 2.9±0.6mm. Durom was tolerant against changes of the cementing technique but showed the widest spread of temperature data 42.8±7.0°C. ReCap showed the highest risk for incomplete seating with a cement mantle thickness of 4.3±0.9mm. Polymerization heat did not exceed the threshold of 45°C with a cement penetration depth of less than 4.2mm in any circumstances of this study.

Breakage of Tapered Junctions of Modular Stems in Revision Total Hip Arthroplasty-High Incidence in a Consecutive Series of a Single Institution.

BACKGROUND: Modularity in revision THA (RTHA) has become accepted during the last three decades. Nevertheless, specific risks of modularity of current revision devices such as breakage of taper junctions occur during follow-up. Data reporting failure rates are predominantly given by the manufacturers but independent data acquisition is missing so far. QUESTIONS/PURPOSES: 1. What time-related risk of breakage of taper junction between neck and body of an established modular revision device can be expected in a consecutive single institutional series and a mid-term follow-up? 2. Are there specific factors influencing breakage in this cohort? MATERIALS AND METHODS: A retrospective analysis was performed of a consecutive series of 89 cases after femoral revision using a tapered modular revision stem. Mean follow-up period was 7.1 (range: 3.0-13.7) years. Breakage of stem as failure criteria of the implant was investigated with a Kaplan-Meier analysis. RESULTS: Breakage of taper junctions occurred in four patients during follow-up showing a time-depending implant survival of 94.2 (95% CI: 88.6-100%) after 13.7 years. Implant survival of stems with lateralized necks of 87.4 (95% CI: 75.6-100%) after 13.7 years was significantly lower compared to the standard offset variant with 100% after 13.5 years (log rank test p = 0.0283). Chi square test also revealed a significantly higher risk of breakage of lateralized necks compared to standard offset pieces (p = 0.0141). Three of four patients were obese with a mean BMI of 37.9 kg/m2. Grade of obesity (grade 1 or higher) had significant influence on risk of breakage. Survival of the implant was significantly lower in obese patients with at least grade 1 obesity compared to patients with a BMI < 30 kg/m2 (82.9 (95% CI: 64.9-100%) after 11.6 years vs. 98.4 (95% CI: 95.3-100%) after 13.7 years; log-rank p = 0.0327). CONCLUSIONS: Cumulative risk for failure of taper junctions was high in this consecutive single institutional cohort and may further increase during follow-up. As independent data acquisition in registries is missing, failure rate may be higher than reported data of the manufacturers. The use of lateralized offset necks in obese patients of at least grade 1 obesity showed a significantly higher risk of breakage. The use of monobloc revision devices may be an option, but randomized control trials are currently missing to establish standardized treatment protocols considering individual risks for both monobloc and/or modular implants.

In vitro cytotoxicity of cyclodextrin-bonded birch bark extract.

Triterpenoids from birch bark, like betulin, seem to have an anticancer potential which needs to be further investigated. Aim of this study was first to explore whether a cyclodextrin-solubilised triterpenoid extract (STE) from birch bark induces selective cytotoxic effects in primary liver cancer cells compared to healthy human hepatocytes. Second, selective cytotoxicity against several tumour cell lines should be analysed. For this purpose, human liver cancer cells derived from mouse xenografts (LIXF 575), healthy human hepatocytes, and 42 different human tumour cell lines were incubated with different concentrations of STE corresponding to 4.3 µM - 137.5 µM betulin (BE). Cytotoxicity was tested with the WST-1 cell proliferation assay, apoptosis with caspase 3/7-activity, and necrosis was determined by the propidiumiodid uptake assay. The pathway of cytotoxic effects was further investigated by immunoblotting of apoptosis inducing factor (AIF) and p53. The monolayer assay was used to analyse selectivity of STE towards different tumour cell lines. STE significantly (p < 0.001) reduced viability and induced apoptosis of LIXF cells in low concentrations corresponding to 8.6 µM BE, while human hepatocytes were affected only in concentrations ≥ 68.8 µM. Cell death occurred in a p53 independent manner, and AIF was not involved. The mean IC50 in the 42 tumour cell lines corresponded to 4.3 µM BE and ranged from 2.05 µM to 8.95 µM BE content. Selectivity was, therefore, rather low. In conclusion, STE exhibits in low concentrations cytotoxicity in a broad spectrum of primary cancer cells and cancer cell lines, which is, at least in LIXF cells, induced by caspase 3/7 mediated apoptosis. STE is far less toxic in hepatocytes. The anticancer potential of STE should be further characterised and also investigated in animal models.

Elucidating Conformation and Hydrogen-Bonding Motifs of Reactive Thiourea Intermediates.

Substituted diphenylthioureas (DPTUs) are efficient hydrogen-bonding organo-catalysts, and substitution of DPTUs has been shown to greatly affect catalytic activity. Yet, both the conformation of DPTUs in solution and the conformation and hydrogen-bonded motifs within catalytically active intermediates, pertinent to their mode of activation, have remained elusive. By combining linear and ultrafast vibrational spectroscopy with spectroscopic simulations and calculations, we show that different conformational states of thioureas give rise to distinctively different N-H stretching bands in the infrared spectra. In the absence of hydrogen-bond-accepting substrates, we show that vibrational structure and dynamics are highly sensitive to the substitution of DPTUs with CF3 groups and to the interaction with the solvent environment, allowing for disentangling the different conformational states. In contrast to bare diphenylthiourea (0CF-DPTU), we find the catalytically superior CF3-substituted DPTU (4CF-DPTU) to favor the trans-trans conformation in solution, allowing for donating two hydrogen bonds to the reactive substrate. In the presence of a prototypical substrate, DPTUs in trans-trans conformation hydrogen bond to the substrate's C=O group, as evidenced by a red-shift of the N-H vibration. Yet, our time-resolved infrared experiments indicate that only one N-H group forms a strong hydrogen bond to the carbonyl moiety, while thiourea's second N-H group only weakly interacts with the substrate. Our data indicate that hydrogen-bond exchange between these N-H groups occurs on the timescale of a few picoseconds for 0CF-DPTU and is significantly accelerated upon CF3 substitution. Our results highlight the subtle interplay between conformational equilibria, bonding states, and bonding lifetimes in reactive intermediates in thiourea catalysis, which help rationalize their catalytic activity.

Crossover from normal to anomalous diffusion in systems of field-aligned dipolar particles.

Using molecular dynamics simulations we investigate the translational dynamics of particles with dipolar interactions in homogenous external fields. For a broad range of concentrations, we find that the anisotropic, yet normal diffusive behavior characterizing weakly coupled systems becomes anomalous both parallel and perpendicular to the field at sufficiently high dipolar coupling and field strength. After the ballistic regime, chain formation first yields cagelike motion in all directions, followed by transient, mixed diffusive-superdiffusive behavior resulting from cooperative motion of the chains. The enhanced dynamics disappears only at higher densities close to crystallization.

Bone cement penetration pattern and primary stability testing in keeled and pegged glenoid components.

BACKGROUND: It has been proposed that bone mineral density has an influence on cement penetration in hip and knee arthroplasty. The hypotheses of this study were that: 1) there is a negative correlation between bone mineral density (BMD) and cement penetration in cemented glenoid components; and 2) that implant design has an influence on cement penetration into the glenoid bone. METHODS: BMD of 10 pairs of fresh frozen scapulas was measured. Micro-computed tomography (micro-CT) scans in 3 different sections were analyzed after implantation of keeled and pegged glenoid components using a 3(rd)-generation cementing technique with a vacuum mixing system. Cement penetration was analyzed and correlated with BMD. Pull-out strength testing was performed to analyze primary stability. RESULTS: The overall peak BMD was 0.6 [g/cm(2)] (range, 0.33-0.98). A strong negative correlation between BMD and mean cement penetration was found for the peg (R(2) = -.83; P < .003) and for the keel group (R(2) = -.81; P < .005). Mean cement penetration was 78.4 mm(2) (range, 60.6-94.2) in the keel and 113.9 mm(2) (range, 78.2-143.4) in the peg group (P < .0001). In all cases, the components were pulled out of the cement mantle, whereas the bone-cement interfaces remained intact. The mean pull-out strength was 1093N (764-1343N) for keeled and 884N (650-1264N) for pegged components (P < .05). CONCLUSION: A modern cementing technique, leading to a deep bonding between bone and cement, is crucial to prevent loosening of glenoid components. The findings of this study might help us to better understand the results of follow-up studies of cemented glenoid implants. Our results could be helpful for the choice of implants in patients with poor bone quality like osteoporosis or rheumatoid arthritis.

The influence of cementing technique in hip resurfacing arthroplasty on the initial stability of the femoral component.

PURPOSE: In clinical and retrieval analyses, over-penetration of cement, incomplete seating of the prosthesis with a resultant polar cement mass, or both, have been associated with early femoral failures of resurfacing arthroplasties. We used human bone specimens to experimentally compare the initial stability of different cementing techniques. METHODS: Twenty-six pairs of fresh frozen femora were prepared for resurfacing using original instruments (DePuy ASR). ASR femoral resurfacing prostheses were implanted using two different cementing techniques: (1) component filling and (2) cement applicator. Real-time measurements of pressure and temperature during implantation, analyses of cement penetration and micro motions under torque application were performed. RESULTS: Applicator use reduced significantly the cement penetration depth (9.2 mm vs 5.3 mm with the applicator, p = 0.001), polar mantle (8.1 mm vs 2.6 mm, p = 0.008), cement defects (3.7 mm vs 0.1 mm, p = 0.008) and interface temperatures (40.3°C vs 33.1°C, p < 0.001 ). Initial rotational stability showed statistically significant less extreme values with the cement applicator technique (range 3.4-51.7 m°/Nm, 11.0-29.7 m°/Nm, p = 0.024). CONCLUSIONS: The cement applicator technique significantly reduces cement defects, incomplete seating, over-penetration and interface temperatures with a more consistent initial stability of the ASR femoral resurfacing prostheses.