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Implantation is an essential issue in orthopedic surgery. Bulk metallic glasses (BMGs), as a kind of novel materials, attract lots of attentions in biological field owing to their comprehensive excellent properties. Here, we show that a Zr61Ti2Cu25Al12 (at. %) BMG (Zr-based BMG) displays the best cytocompatibility, pronounced positive effects on cellular migration, and tube formation from in-vitro tests as compared to those of commercial-pure titanium and poly-ether-ether-ketone. The in-vivo micro-CT and histological evaluation demonstrate the Zr-based BMG can significantly promote a bone formation. Immunofluorescence tests and digital reconstructed radiographs manifest a stimulated effect on early blood vessel formation from the Zr-based BMG. Accordingly, the intimate connection and coupling effect between angiogenesis and osteogenesis must be effective during bone regeneration after implanting Zr-based BMG. Dynamic gait analysis in rats after implanting Zr-based BMG demonstrates a tendency to decrease the pain level during recovery, simultaneously, without abnormal ionic accumulation and inflammatory reactions. Considering suitable mechanical properties, we provide a realistic candidate of the Zr61Ti2Cu25Al12 BMG for biomedical applications.

Dense and crack-free specimens of the shape memory alloy Cu71.6Al17Mn11.4 (at.%) were produced via laser powder bed fusion across a wide range of process parameters. The microstructure, viz. grain size, can be directly tailored within the process and with it the transformation temperatures (TTs) shifted to higher values by raising the energy input. The microstructure, and the superelastic behavior of additively manufactured samples were assessed by a detailed comparison with induction melted material. The precipitation of the α phase, which inhibit the martensitic transformation, were not observed in the additively manufactured samples owing to the high intrinsic cooling rates during the fabrication process. Fine columnar grains with a strong [001]-texture along the building direction lead to an enhanced yield strength compared to the coarse-grained cast samples. A maximum recoverable strain of 2.86% was observed after 5% compressive loading. The first results of our approach imply that laser powder bed fusion is a promising technique to directly produce individually designed Cu-Al-Mn shape memory parts with a pronounced superelasticity at room temperature.

Nearly fully dense, glassy Zr52.5Cu17.9Ni14.6Al10Ti5 bulk specimens were fabricated by selective laser melting (SLM) and their behaviour during compressive loading, during wear testing and in a corrosive medium was investigated. Their performance was compared with as-cast material of the same composition. The additively manufactured samples exhibit a yield strength around 1700 MPa combined with a plastic strain of about 0.5% after yielding despite the residual porosity of 1.3%, which is distributed uniformly in the samples. The propagation of shear bands in the bulk metallic glass prepared by SLM was studied. The specific wear rate and the worn surfaces demonstrated that similar wear mechanisms are active in the SLM and the as-cast samples. Hence, manufacturing the glass in layers does not adversely affect the wear properties. The same holds for the corrosion tests, which were carried out in 0.01 M Na2SO4 and 0.1 M NaCl electrolyte. The anodic polarization curves of SLM samples and as-cast samples revealed a similar corrosion behaviour. However, the SLM samples have a slightly reduced susceptibility to pitting corrosion and exhibit an improved surface healing ability, which might be attributed to an improved homogeneity of the additively manufactured glass. Keywords: Selective laser melting, Zr-based alloy, Microhardness, Compression tests, Wear resistance, Corrosion resistance

Abstract We developed a temperature-controlled inductive flash-annealing device, which heats bulk metallic glasses (BMGs) at defined rates of up to 200 K/s to a given temperature. Subsequent instantaneous quenching in water allows preserving the microstructures obtained at various stages of crystallization. One Zr-based and two CuZr-based BMGs were flash-annealed at the onset of crystallization with different heating rates in order to prepare advanced BMG-matrix composites. The highly reproducible composite microstructures contain uniformly dispersed crystals and a narrow crystal size distribution. In order to assess the limitations of the present process, which mainly originate from non-uniform inductive heating, the skin depth was calculated. It is determined to be about 2.3 mm, which enables flash-annealing of rather bulky samples. The cooling rate was estimated from the interlamellar spacing of eutectic Al-Cu alloys to be on the order of 103 K/s. This ensures that decomposition of the microstructure during quenching is prevented. The present flash-annealing procedure is applicable to a wide variety of glass-forming liquids and has a large potential for tailoring the microstructure and, consequently, the mechanical properties of BMG-matrix composites.

The structural evolution of Ti50Cu43Ni7 and Ti55Cu35Ni10 metallic glasses during heating was investigated by in-situ synchrotron X-ray diffraction. The width of the most intense diffraction maximum of the glassy phase decreases slightly during relaxation below the glass transition temperature. Significant structural changes only occur above the glass transition manifesting in a change in the respective peak positions. At even higher temperatures, nanocrystals of the shape memory B2-Ti(Cu,Ni) phase precipitate, and their small size hampers the occurrence of a martensitic transformation.

L'Auvergne est une région agricole avec 26 000 km2 et 1,5 million d'hectares de surface agricole utile. Elle comprend deux systèmes de production qui nécessitent des produits organiques pour assurer le niveau de matière organique des sols cultivés : les grandes cultures en plaine de Limagnes et le système polycultures/élevage en montagne. Dans le contexte de refus d'épandre ou de demande de dérogation à la réglementation des boues urbaines, les objectifs du projet sont de déterminer l'impact de l'épandage des boues en conditions agricoles réelles sur la productivité et sur les teneurs en éléments traces métalliques (ETM). Nos travaux confirment l'intérêt de l'apport de boues sur les sols agricoles en augmentant la production finale de matière sèche et en jouant sur les différents stades d'établissement du rendement dès la première année d'épandage. À ce stade, ils ne révèlent pas de risque direct de contamination métallique des plantes par l'épandage de boues réalisé dans les conditions réglementaires. La variabilité des résultats relatifs à l'impact des boues sur la productivité et sur le transfert sol/plante des ETM d'une année à l'autre et d'un site à l'autre a conduit à constituer une base de données en ETM avec un seuil de teneurs par espèce et par élément. Dans le futur, les données devront être étendues à d'autres espèces annuelles. L'objectif final est de raisonner les pratiques agricoles et particulièrement la gestion des apports organiques dans le respect de la qualité de la production végétale et de son environnement.

The variation of the transformation-mediated deformation behavior with microstructural changes in CuZr-based bulk metallic glass composites is investigated. With increasing crystalline volume fraction, the deformation mechanism gradually changes from a shear-banding dominated process as evidenced by a chaotic serrated flow behavior, to being governed by a martensitic transformation with a pronounced elastic-plastic stage, resulting in different plastic deformations evolving into a self-organized critical state characterized by the power-law distribution of shear avalanches. This is reflected in the stress-strain curves by a single-to-“double”-to-“triple”-double yielding transition and by different mechanical properties with different serrated flow characteristics, which are interpreted based on the microstructural evolutions and a fundamental energy theorem. Our results can assist in understanding deformation behaviors for high-performance metastable alloys.

In-situ dendrite/metallic glass matrix composites (MGMCs) with a composition of Ti46Zr20V12Cu5Be17 exhibit ultimate tensile strength of 1510 MPa and fracture strain of about 7.6%. A tensile deformation model is established, based on the five-stage classification: (1) elastic-elastic, (2) elastic-plastic, (3) plastic-plastic (yield platform), (4) plastic-plastic (work hardening), and (5) plastic-plastic (softening) stages, analogous to the tensile behavior of common carbon steels. The constitutive relations strongly elucidate the tensile deformation mechanism. In parallel, the simulation results by a finite-element method (FEM) are in good agreement with the experimental findings and theoretical calculations. The present study gives a mathematical model to clarify the work-hardening behavior of dendrites and softening of the amorphous matrix. Furthermore, the model can be employed to simulate the tensile behavior of in-situ dendrite/MGMCs. [ABSTRACT FROM AUTHOR]

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The incidence of rotator cuff tears and recurrent defects positively correlate with patient age. However, this observation has never been analysed at the cellular level. The present study aims to better understand this correlation by investigating cellular characteristics of rotator cuff tenocytes of different age groups. Additionally, previous studies reported on stimulating effects of Bone Morphogenetic Protein (BMP) -2 and BMP-7 on tenocytes. Thus, the second aim was to investigate, whether the stimulation potential of tenocytes demonstrates age-related differences.Tenocyte-like cells from supraspinatus tendons of young and aged patients were analysed for the following cell biological characteristics: cell density, cell growth, marker expression, collagen-I protein synthesis, stem cell phenotype, potential for multipotent differentiation and self-renewal. To analyse the stimulation potential, cells were treated with BMP-2 and BMP-7 in 2D-/3D-cultures. Measured parameters included cell activity, marker expression and collagen-I protein synthesis.An effect of age was seen for cell growth and stem cell potential but not on extracellular matrix level. Cells from both groups responded to BMP-7 by increasing cell activity, collagen-I expression and protein synthesis. BMP-2 led to smaller increases in these parameters when compared to BMP-7. In general, 3D-cultivation improved the stimulation compared to 2D-culture.The cell biological characteristics of tenocyte-like cells, considered important for successful restoration of the tendon-bone unit, were inferior in elderly donors. This may help explain higher rates of recurrent defects seen in elderly patients. Regarding the stimulation potential, on a cellular level young and aged patients may benefit from biological augmentation with BMPs.

tator cuff tears are common soft tissue injuries of the musculoskeletal system that heal by formation of repair tissue and may lead to high retear rates and joint dysfunction. In particular, tissue from chronic, large tendon tears is of such degenerative nature that it may be prone to retear after surgical repair. Besides several biomechanical approaches, biologically based strategies such as application of growth factors may be promising for increasing cell activity and production of extracellular tendon matrix at the tendon-to-bone unit. As a precondition for subsequent experimental growth factor application, the aim of the present study was to establish and characterize a human rotator cuff tendon cell culture.Long head biceps (LHB)- and supraspinatus muscle (SSP)- tendon samples from donor patients undergoing shoulder surgery were cultivated and examined at the RNA level for expression of collagen type-I, -II and -III, biglycan, decorin, tenascin-C, aggrecan, osteocalcin, tenomodulin and scleraxis (by Real-time PCR). Finally, results were compared to chondrocytes and osteoblasts as control cells.An expression pattern was found which may reflect a human rotator cuff tenocyte-like cell culture. Both SSP and LHB tenocyte-like cells differed from chondrocyte cell cultures in terms of reduced expression of collagen type-II (p≤0.05) and decorin while higher levels of collagen type-I were seen (p≤0.05). With respect to osteoblasts, tenocyte-like cells expressed lower levels of osteocalcin (p≤0.05) as well as tenascin C, biglycan and collagen type-III. Expression of scleraxis, tenomodulin and aggrecan was similar between all cell types.This study represents a characterization of tenocyte-like cells from the human rotator cuff as close as possible. It helps analyzing their biological properties and allows further studies to improve production of tendon matrix and osteofibroblastic integration at the tendon-bone unit following tendon repair.

Objective: With advances in techniques, arthroscopic repair of isolated subscapularis tendon tears has become increasingly popular in recent years. The aim of this study was to analyze the clinical and structural results of arthroscopic repair versus the gold standard of open repair. It is a prospective cohort study with a control group; evidence level III. Methods: In a prospective study performed at two centers, 18 patients with an isolated subscapularis tear were treated with arthroscopic repair (ARG) and 16 patients with open repair (ORG) using a uniform single-row suture anchor repair technique in both groups. The subscapularis function was assessed using specific clinical tests (belly-press and lift-off tests), strength testing and shoulder function with the use of the Constant-Murley score (CMS). Standardized magnetic resonance imaging (MRI) was used to evaluate the postoperative subscapularis muscle-tendon status. Results: At a minimum follow-up of 48 months, the CMS increased from a mean of 54 points preoperatively to a mean of 86 points postoperatively in the ARG ( p < 0.01) and from 50 points to 85 points postoperatively in the ORG ( p < 0.01). Specific subscapularis tests (belly-press test and lift-off test) were significantly improved from the preoperative to the postoperative status in both repair groups ( p < 0.05). Despite a subscapularis tendon healing rate of over 90% on MRI scans in both repair groups, the incomplete correction of specific muscle tests was a frequent postoperative finding. Conclusions: Arthroscopic repair of isolated subscapularis tears achieved equivalent clinical and structural results compared to the gold standard of open repair.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses. The rRNA synthesis (RS) ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, together with solid culture CFU counts and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time-course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development., Competing Interests: N.D.W. and G.T.R. are listed as co-inventors on US patent no. 16/632,310 which pertains to the RS ratio.

Alternating pressure support surface (APSS) is a common support surface for treating pressure injury in individuals with spinal cord injury (SCI). However, conflicting results on the effectiveness of APSS have been reported and may be associated with inappropriate configurations of APSS. The objectives of this study were to compare the different pressure amplitudes (75/5 mmHg [alternating between 75 and 5 mmHg] vs. 65/15 mmHg) and cycle periods (5 min [4 cycles] vs. 2.5 min [8 cycles]) of alternating pressure on sacral skin blood flow responses in 10 individuals with SCI. Sacral skin blood flow during and after loading of four alternating pressure protocols was assessed using laser Doppler flowmetry and was normalised to the value before loading (10-min baseline, 20-min loading and 10-min recovery). The results demonstrated that during the high-pressure phase, there was a significant difference between the 75/5 and 65/15 mmHg protocols (0.3658 ± 0.0688 for 75/5 mmHg and 0.1702 ± 0.0389 for 65/15 mmHg, p < 0.05); and during the low-pressure phase, there was a significant difference between the 75/5 and 65/15 mmHg protocols (1.7184 ± 0.262 for 75/5 mmHg and 0.5916 ± 0.1378 for 65/15 mmHg, p < 0.05). There were no differences between cycle periods in skin blood flow responses. No adverse events were reported. Our finding indicates that the pressure amplitude of alternating pressure is a significant factor affecting sacral skin blood flow responses. An appropriate configuration of alternating pressure is needed to effectively increase skin blood flow and tissue viability in individuals with SCI., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Mechanistic probing of surface potential changes arising from dynamic charge transport is the key to understanding and engineering increasingly complex nanoscale materials and devices. Spatiotemporal averaging in conventional heterodyne detection-based Kelvin probe force microscopy (KPFM) inherently limits its time resolution, causing an irretrievable loss of transient response and higher-order harmonics. Addressing this, we report a wavelet transform (WT)-based methodology capable of quantifying the sub-ms charge dynamics and probing the elusive transient response. The feedback-free, open-loop wavelet transform KPFM (OL-WT-KPFM) technique harnesses the WT's ability to simultaneously extract spatial and temporal information from the photodetector signal to provide a dynamic mapping of surface potential, capacitance gradient, and dielectric constant at a temporal resolution 3 orders of magnitude higher than the lock-in time constant. We further demonstrate the method's applicability to explore the surface-photovoltage-induced sub-ms hole-diffusion transient in bismuth oxyiodide semiconductor. The OL-WT-KPFM concept is readily applicable to commercial systems and can provide the underlying basis for the real-time analysis of transient electronic and electrochemical properties.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen (bedaquiline-pretomanid-linezolid [BPaL]) during the first three weeks of treatment at human equivalent doses. RS ratio, an exploratory pharmacodynamic (PD) marker of ongoing Mycobacterium tuberculosis rRNA synthesis, to-gether with solid culture CFU and liquid culture time to positivity (TTP) were used as PD markers of treatment response in lung tissue; and their time course profiles were mathematically modeled using rate equations with pharmacologically interpretable parameters. Antimicrobial interactions were quantified using Bliss independence and Isserlis formulas. Subadditive (or antagonistic) and additive effects on bacillary load, assessed by CFU and TTP, were found for bedaquiline-pretomanid and linezolid-containing pairs, respectively. In contrast, subadditive and additive effects on rRNA synthesis were found for pretomanid-linezolid and bedaquiline-containing pairs, respectively. Additionally, accurate predictions of the response to BPaL for all three PD markers were made using only the single-drug and pairwise effects together with an assumption of negligible three-way drug interactions. The results represent an experimental and PD modeling approach aimed at reducing combinatorial complexity and improving the cost-effectiveness of in vivo systems for preclinical TB regimen development.

The study aimed to analyze the stress/strain distribution of new designs of mini-implants manufactured by machining and additive manufacturing. Four designs were evaluated (Ø2.0 mm × 10 mm): Intra-lock, helical, threaded machined (MN threaded) and threaded by additive manufacturing (AM threaded). Analysis of stress was performed through photoelastic analysis (100 N axial/oblique loads) and analysis of strain by digital image correlation (DIC) (250 N axial/100 N oblique load). Data distribution was verified using the Shapiro-Wilk test and a significance level of 5% was adopted. Quantitative data were analyzed using the non-parametric Kruskal-Wallis test. In photoelastic analysis, the Intra-lock mini-implant showed the highest stresses in the cervical (104 kPa), middle (108 kPa), and apical (212 kPa) thirds. Higher stresses were observed in the oblique loading situation for all designs. For DIC analysis, axial loading, a significant difference was observed for the AM Threaded mini-implants about the other designs in the cervical third (p = .04), with the highest strain value 47 με [10; 76]. In oblique loading, a significant difference between the mini-implants was observed in the middle and apical thirds, with higher strains for the AM threaded design -185 με [-173; 162] (p = .009) and 242 με [87; 372] (p = .013), respectively. In general, the influence of different mini-implant designs and the additive manufacturing method on the stress/strain was observed, in the photoelastic and DIC analysis. The evaluated designs demonstrated a lower concentration of stress/strain in the cervical region compared to the apical region, and higher stress/strain in situations of oblique load compared with axial load., (© 2023 Wiley Periodicals LLC.)

Tuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics in pulmonary lesions, but the bacterial phenotypes that arise under these conditions and their contribution to drug tolerance are poorly understood. A pharmacodynamic marker called the RS ratio ® quantifies ongoing rRNA synthesis based on the abundance of newly synthesized precursor rRNA relative to mature structural rRNA. Application of the RS ratio in the C3HeB/FeJ mouse model demonstrated that Mycobacterium tuberculosis populations residing in different tissue microenvironments are phenotypically distinct and respond differently to drug treatment with rifampin, isoniazid, or bedaquiline. This work provides a foundational basis required to address how anatomic and pathologic microenvironmental niches may contribute to long treatment duration and drug tolerance during the treatment of human tuberculosis., Competing Interests: N.W.D., M.I.V., and G.T.R. are listed as co-inventors on US patent No. 16/632,310 that pertains to the RS ratio. The remaining authors have no conflicts of interest to declare.

Cupping therapy has been widely used to manage musculoskeletal impairment. However, the effects of pressure and duration of cupping therapy on the hemodynamic activity of the muscle have not been investigated. A 2 × 2 repeated measures factorial design was used to examine the main effect and interaction of pressure (-225 and -300 mmHg) and duration (5 and 10 min) on biceps muscle blood flow using near-infrared spectroscopy in 18 participants. The results showed that a significant interaction is between pressure and duration on deoxy-hemoglobin (p = 0.045). A significant main effect of pressure is on oxyhemoglobin (p = 0.005) and a significant main effect of duration is on oxyhemoglobin (p = 0.005). Cupping therapy at -300 mmHg for 10 min results in a higher oxyhemoglobin (6.75 ± 2.08 μM) and deoxy-hemoglobin (1.71 ± 0.78 μM) compared to other three combinations. Our study provides first evidence that the pressure and duration factors of cupping therapy can significantly affect muscle blood volume and oxygenation., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

The management of proximal tibial fractures has evolved significantly in recent years. While the main goals of treatment - stability, restoration of the mechanical axis, and smooth articular surfaces - remain the same, methods have advanced substantially. In diagnostics, technical progress in CT and MR imaging has led to a better three-dimensional understanding of the injury. Newly developed classification systems such as the three-column concept of Luo et al. and the 10-segment concept of Krause et al. take this into account. Accordingly, there is a trend towards tailored approaches for particular fracture localizations. Parallel to this development, there is increasing evidence of the advantages of arthroscopically assisted surgical procedures. This Current Concepts article reviews classifications, diagnostics, treatment options as well as complications in fractures of the proximal tibia., Competing Interests: SK is member of the speaker’s bureau of Smith & Nephew, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gahr, Kopf and Pauly.)

Localized surface plasmon resonance (LSPR) of metallic nanostructures is a unique phenomenon that controls the light in sub-wavelength volumes and enhances the light-matter interactions. Traditionally, the excitation and measurement of LSPR require bulky external light sources, and efforts to scale down to nano-plasmonic devices have predominantly relied on the system's miniaturization and associated accessories. Addressing this, here we show the generation and detection of LSPR wavelength (λ LSPR ) shifts in large-area nanostructured Au surfaces using frictional charges generated by triboelectric surfaces. We observe a complex interplay of the localized surface plasmons with frictional charges via concurrent spectroscopic and triboelectric measurements undertaken for the detection of bioconjugation in the streptavidin-biotin complex. When subjected to multivariate principal component analysis, a strong correlation between the triboelectric peak-to-peak voltage output response and the λ LSPR shift is observed. Furthermore, we reveal a landscape of the interfacial events involved in the electrical generation/detection of the LSPR by using theoretical models and surface characterization. The demonstrated concept of electrification of plasmon resonance thus provides the underlying basis for the subsequent development of self-powered nano-plasmonic sensors and opens new horizons for advanced nanophotonic applications.

Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on CFU of Mycobacterium tuberculosis in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies drug effect on a fundamental cellular process, ongoing rRNA synthesis. Here, we evaluated the ability of different pharmacodynamic markers to distinguish between treatments in three BALB/c mouse experiments at two institutions. We confirmed that different pharmacodynamic markers measure distinct biological responses. We found that a combination of pharmacodynamic markers distinguishes between treatments better than any single marker. The combination of the RS ratio with CFU showed the greatest ability to recapitulate the rank order of regimen treatment-shortening activity, providing proof of concept that simultaneous assessment of pharmacodynamic markers measuring different properties will enhance insight gained from animal models and accelerate development of new combination regimens. These results suggest potential for a new era in which antimicrobial therapies are evaluated not only on culture-based measures of bacterial burden but also on molecular assays that indicate how drugs impact the physiological state of the pathogen.

Aims: Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI., Methods: From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined., Results: Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures)., Conclusion: Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open  2021;2(8):671-678.

The surface properties of titanium and its alloys are commonly modified by different techniques, including additive manufacturing (AM), to improve the osseointegration of dental implants. The aim of this study was to evaluate and compare the wettability, topography, chemistry, and structure of titanium-aluminum-vanadium (Ti-6Al-4 V) discs fabricated by selective laser melting (SLM) and subtractive manufacturing (conventional machining). Three different groups were evaluated: selective laser melting (SLM); conventional machining with H 3 PO 4  + NaOH surface treatment (CM + ST); and conventional machining without surface treatment (CM), including analysis of wettability and roughness, morphological and chemical analyses by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), and structural characterization analysis by computed tomography (micro-CT), and X-ray diffraction (XRD). The results showed that SLM surface had higher roughness (9.09 ± 1.94 Ra; 51.93 ± 11.59 Rz; 11.03 ± 1.95 Sa) and lower wettability (103.23° ± 13) than CM (0.06 ± 0.01 Ra; 0.42 ± 0.078 Rz; 0.07 ± 0.01 Sa) (76.95° ± 4.18) and CM + ST (0.17 ± 0.38 Ra; 0.88 ± 0.15 Rz; 0.18 ± 0.04 Sa) (18.55° ± 6.47) (p < 0.05). SEM images also proved the higher roughness of SLM surface, and CM + ST discs showed a topography resembling a sponge, characteristic of the nanometric treatment applied. EDX and XRD found no differences between the different surfaces, and micro-CT demonstrated the solid characteristic of the SLM disc. Compared with conventional machining, the SLM technique resulted in higher roughness and lower wettability. Meanwhile, the chemical properties and structure of the titanium alloy was not altered by the technique., (© 2020 Wiley Periodicals LLC.)

Background: Treatment of first-time shoulder dislocation (FSD) is a topic of debate. After high rates of recurrent instability after nonoperative management were reported in the literature, primary repair of FSD significantly increased. At the same time, new concepts were proposed that had promising results for immobilization in external rotation (ER) and abduction (ABD)., Purpose: The aim of this study was to evaluate the recurrence rates (primary outcome) and clinical outcomes (secondary outcome parameters) of immobilization in ER+ABD versus arthroscopic primary stabilization after FSD., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: In a multicenter randomized controlled trial, patients with FSD were randomized to either treatment with immobilization in 60° of ER plus 30° of ABD (group 1) or surgical treatment with arthroscopic Bankart repair (group 2). Clinical evaluation was performed 1, 3, and 6 weeks as well as 6, 12, and 24 months postoperatively or after reduction, including range of motion, instability testing, subjective shoulder value, Constant-Murley score, Rowe score, and Western Ontario Shoulder Instability Index. Recurrent instability events were prospectively recorded., Results: Between 2011 and 2017, a total of 112 patients were included in this study. Of these, 60 patients were allocated to group 1 and 52 to group 2. At the 24-month follow-up, 91 patients (81.3%) were available for clinical examination. The recurrence rate was 19.1% in group 1 and 2.3% in group 2 ( P = .016). No significant differences were found between groups regarding clinical shoulder scores ( P > .05). Due to noncompliance with the immobilization treatment protocol, 4 patients (6.7%) were excluded., Conclusion: Immobilization in ER+ABD versus primary arthroscopic shoulder stabilization for the treatment of FSD showed no differences in clinical shoulder scores. However, recurrent instability was significantly higher after nonoperative treatment.

Panel data covering the French population before and after the outbreak of the Covid-19 epidemic reveal that self-reported health and well-being have improved during the lockdown in comparison to previous years. We name this counterintuitive phenomenon the "eye of the hurricane" paradox: the large majority of individuals who are not infected by the virus may be seeing their current condition in a more positive light than they normally would. There are, however, divergences across social groups that reflect socioeconomic inequalities. In particular, blue-collar workers deviate from the prevailing trend as their level of self-reported health declines over the lockdown period, Parisian residents experience a sudden drop in their subjective well-being, and people working long hours at home exhibit higher levels of stress during the quarantine., (© 2020 Elsevier Ltd. All rights reserved.)

Although several studies revealed a multifactorial pathogenesis of degenerative rotator cuff disorders, the impact and interaction of extrinsic variables is still poorly understood. Thus, this study aimed at uncovering the effect of patient- and pathology-specific risk factors that may contribute to degeneration of the rotator cuff tendons. Between 2015 and 2018, 54 patients who underwent arthroscopic shoulder surgery at three specialized shoulder clinics were prospectively included. Using tendon samples harvested from the macroscopically intact subscapularis (SSC) tendon, targeted messenger RNA expression profile analysis was performed in the first cohort (n = 38). Furthermore, histological analyses were conducted on tendon tissue samples obtained from a second cohort (n = 16). Overall, both study cohorts were comparable concerning patient demographics. Results were then analyzed with respect to specific extrinsic factors, such as patient age, body mass index, current as well as previous professions and sport activities, smoking habit, and systemic metabolic diseases. While patient age, sports-activity level, and preexisting rotator cuff lesions were considered to contribute most strongly to tendinopathogenesis, no further coherences were found. With regards to gene expression analysis, change in expression correlated most strongly with patient age and severity of the rotator cuff pathology. Further, chronic disorders increased overall gene expression variation. Taken together, our study provides further evidence that tendon degeneration is the consequence of a multifactorial process and pathological changes of the supraspinatus tendon affect the quality of SSC tendon and most likely vice versa. Therefore, the rotator cuff tendons need to be considered as a unit when managing rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:182-191, 2020., (© 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.)

Background: Pathologic activation pattern of muscles can cause shoulder instability. We propose to call this pathology functional shoulder instability (FSI). The purpose of this prospective study was to provide an in-detail description of the characteristics of FSI., Methods: In the year 2017, a total of 36 consecutive cases of FSI presenting to our outpatient clinic were prospectively collected. Diagnostic investigation included a pathology-specific questionnaire, standardized clinical scores, clinical examination, psychological evaluation, video and dynamic fluoroscopy documentation of the instability mechanism, as well as magnetic resonance imaging (MRI). In a final reviewing process, the material from all collected cases was evaluated and, according to the observed pattern, different subtypes of FSI were determined and compared., Results: Based on the pathomechanism, positional FSI (78%) was distinguished from nonpositional FSI (22%). Controllable positional FSI was observed in 6% of all cases and noncontrollable positional FSI in 72%, whereas controllable and noncontrollable nonpositional FSI were each detected in 11% of the cases. The different subtypes of FSI showed significant differences in all clinical scores (Western Ontario Shoulder Instability Index: P = .002, Rowe Score: P = .001, Subjective Shoulder Value: P = .001) and regarding functional impairment (shoulder stability: P < .001, daily activities: P = .001, sports activities: P < .001). Seventy-eight percent had posterior, 17% anterior, and 6% multidirectional instability. Although several patients showed constitutional glenoid shape alterations or soft tissue hyperlaxity, only few patients with acquired minor structural defects were observed., Conclusion: FSI can be classified into 4 subtypes based on pathomechanism and volitional control. Depending on the subtype, patients show different degrees of functional impairment. The majority of patients suffer from unidirectional posterior FSI., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Reverse shoulder arthroplasty shifts the rotational center of the shoulder joint caudally and medially to restore shoulder function in a rotator cuff deficient shoulder. Despite promising results in early- and mid-term follow-up, long-term loss in shoulder function has been described in the literature. A lack of exercise in elderly patients may be one reason for this loss in function. This study examines the functional benefits of physical therapy in the mid-term to long-term follow-up regarding the subjective and objective shoulder function., Materials and Methods: Twenty patients with a mean age of 73 years were included in this series. The study was performed as a single-center, prospective study. Initial indications for reverse shoulder arthroplasty were cuff tear arthropathy, failed anatomical shoulder arthroplasty, and fracture sequelae. The patients were clinically examined at a mean follow-up of 62 months using the Constant score (CS) and the DASH score for the operated and the non-operated shoulder. They were reevaluated using the same scores following a standardized physical therapy program of 6 weeks' duration., Results: The mean CS as well as the mean age- and gender-adjusted CS of the affected shoulder improved significantly from 53.5 to 59.3 points, and 72.7-80.8%, respectively. The subcategories activities of daily living (ADL) and range of motion (ROM) of the CS improved significantly, whereas no significant improvement was observed for the subcategories pain and strength. Evaluating the contralateral shoulder, no significant change was observed for the age- and gender-adjusted CS and the CS as well as its subcategories. We found no significant difference in the CS comparing the different etiologies prior to physical therapy., Discussion: Physical therapy plays an important role subsequent to reverse shoulder arthroplasty. It also has an effect in the mid-term to long-term follow-up regarding the range of motion as well as activities of daily living. However, physical therapy seems to have limited effect on the strength and the residual pain level., Level of Evidence: Level III.

Background: Platelet rich plasma (PRP) is widely used in rotator cuff repairs but its effect on the healing process is unclear. Several cell culture studies on the effect of allogenic PRP have reported promising results but are not transferable to clinical practice. The aim of the present study is to assess the possible effect of autologous PRP on rotator cuff tendon cells. The amount of growth factors involved with tendon-bone healing (PDGF-AB, IGF-1, TGF-β1, BMP-7 and -12) is quantified., Methods: Rotator cuff tissue samples were obtained from (n = 24) patients grouped by age (>/< 65 years) and sex into four groups and cells were isolated and characterized. Later, autologous PRP preparations were obtained and the effect was analyzed by means of cell proliferation, collagen I synthesis and expression of collagen I and III. Furthermore, the PRPs were quantified for growth factor content by means of platelet-derived growth factor (PDGF-AB), insulin-like growth factor (IGF-1), transforming growth factor (TGF-β1), as well as bone morphogenetic protein (BMP) -7 and - 12., Results: Cell proliferation and absolute synthesis of collagen I were positively affected by PRP exposure compared to controls (p < 0.05), but expression and relative synthesis of collagen I (normalized to cell proliferation) were significantly reduced. PRP contained high amounts of IGF-1 and lower levels of TGF-β1 and PDGF-AB. The amounts of BMP-7 and -12 were below the detection limits., Conclusions: PRP is a source of growth factors such involved with tendon-bone healing. PRP had an anabolic effect on the human rotator cuff tenocytes of the same individual in vitro by means of cell proliferation and absolute, but not relative collagen I synthesis. These results encourage further studies on clinical outcomes with more comparable standards in terms of preparation and application methods., Level of Evidence: Controlled laboratory study.

Objective: Reconstruction of tendon integrity to maintain glenohumeral joint centration and hence to restore shoulder functional range of motion and to reduce pain., Indications: Isolated or combined full-thickness subscapularis tendon tears (≥upper two-thirds of the tendon) without both substantial soft tissue degeneration and cranialization of the humeral head., Contraindications: Chronic tears of the subscapularis tendon with higher grade muscle atrophy, fatty infiltration, and static decentration of the humeral head., Surgical Technique: After arthroscopic three-sided subscapularis tendon release, two double-loaded suture anchors are placed medially to the humeral footprint. Next to the suture passage, the suture limbs are tied and secured laterally with up to two knotless anchors creating a transosseous-equivalent repair., Postoperative Management: The affected arm is placed in a shoulder brace with 20° of abduction and slight internal rotation for 6 weeks postoperatively. Rehabilitation protocol including progressive physical therapy from a maximum protection phase to a minimum protection phase is required. Overhead activities are permitted after 6 months., Results: While previous studies have demonstrated superior biomechanical properties and clinical results after double-row compared to single-row and transosseous fixation techniques, further mid- to long-term clinical investigations are needed to confirm these findings.

ZrCu-based bulk metallic glass composites (BMGCs) are well known for their plastic deformability, superior to traditional metallic glasses (MGs), which is attributed to a unique dual-phases structure, namely, the glassy matrix and unstable B2 phase. In the present study, in-situ tensile testing is used to trace the deformation process of a ZrCu-based BMGC. Three deformation stages of the BMGC, i.e., the elastic-elastic stage, the elastic-plastic stage, and the plastic-plastic stage are identified. In the elastic-elastic and elastic-plastic stages, the yield strength and elastic limit are major influenced by the volume fraction of the B2 crystals. In the plastic-plastic stage, the B2 phase stimulates the formation of multiple shear bands and deflects the direction of shear bands by disturbing the stress field in front of the crack tip. The deformation-induced martensitic transformation of the metastable B2 phase contributes to the plasticity and work hardening of the composite. This study highlights the formation and propagation of multiple shear bands and reveals the interactions of shear bands with structural heterogeneities in situ. Especially, the blocking of shear bands by crystals and the martensitic transformation of the B2 phase are critical for the mechanistic deformation process and illustrate the function of the B2 phase in the present BMGCs.

Martensitic transformations originate from a rigidity instability, which causes a crystal to change its lattice in a displacive manner. Here, we report that the martensitic transformation on cooling in Ti-Zr-Cu-Fe alloys yields an amorphous phase instead. Metastable β-Ti partially transforms into an intragranular amorphous phase due to local lattice shear and distortion. The lenticular amorphous plates, which very much resemble α'/α″ martensite in conventional Ti alloys, have a well-defined orientation relationship with the surrounding β-Ti crystal. The present solid-state amorphization process is reversible, largely cooling rate independent and constitutes a rare case of congruent inverse melting. The observed combination of elastic softening and local lattice shear, thus, is the unifying mechanism underlying both martensitic transformations and catastrophic (inverse) melting. Not only do we reveal an alternative mechanism for solid-state amorphization but also establish an explicit experimental link between martensitic transformations and catastrophic melting.

This present article summarizes established and current developments and aspects of rotator cuff surgery. Achieved milestones as well as current approaches are presented and assessed with respect to their clinical and radiographic impact. Despite biomechanical and technical improvements in modern rotator cuff repair techniques, re-defect and re-tearing rates could not be fully eliminated. Meanwhile, the importance of biological processes around successful tendon-bone reintegration has been increasingly recognized. Hence, this article presents the current scientific standing regarding biological growth factors, platelet-rich plasma and rotator cuff augmentation techniques (with allogenic/autologous grafts). In summary, there are clear biomechanical advantages as well as many promising approaches to biological augmentation; however, the latter have not yet been transferred into regular clinical application.

Fluctuation electron microscopy of bulk metallic glasses of CuZrAl(Ag) demonstrates that medium-range order is sensitive to minor compositional changes. By analyzing nanodiffraction patterns medium-range order is detected with crystal-like motifs based on the B2 CuZr structure and its distorted structures resembling the martensitic ones. This result demonstrates some structural homology between the metallic glass and its high temperature crystalline phase. The amount of medium-range order seems slightly affected with increasing Ag concentration (0, 2, 5 at.%) but the structural motifs of the medium-range ordered clusters become more diverse at the highest Ag concentration. The decrease of dominant clusters is consistent with the destabilization of the B2 structure measured by calorimetry and accounts for the increased glass-forming ability.

Unlike crystalline metals, the plastic deformation of metallic glasses (MGs) involves a competition between disordering and structural relaxation ordering, which is not well understood, yet. Molecular dynamics (MD) simulations were performed to investigate the evolutions of strain localizations, short-range order (SRO) as well as the free volume in the glass during compressive deformation of Fe 50 Cu 50 MGs with different degrees of phase separation. Our findings indicate that the free volume in the phase separating MGs decreases while the shear strain localizations increase with increasing degree of phase separation. Cu-centered clusters show higher potential energies and Voronoi volumes, and bear larger local shear strains. On the other hand, Fe-centered pentagon-rich clusters in Cu-rich regions seem to play an important role to resist the shear transformation. The dilatation or annihilation of Voronoi volumes is due to the competition between ordering via structural relaxation and shear stress-induced deformation. The present study could provide a better understanding of the relationship between the structural inhomogeneity and the deformation of MGs.

Purpose and Hypothesis: This study evaluates the functional and cosmetic results following fixation of the long head of the biceps (LHB) tendon at the antero-medial footprint anchor of a rotator cuff reconstruction, using the "lasso-loop" technique., Methods: 39 patients with a mean age of 62 years with a rotator cuff tear and associated lesion of the LHB tendon were included in this study. Besides rotator cuff repair in an arthroscopic anchor technique, all patients received additional LHB tenodeses using the lasso-loop technique. Clinical follow-up consisted of the Constant score (CS), LHB score, DASH score, and WORC index. Relevant sub-items, such as elbow flexion strength and cosmesis, were compared to the contralateral arm., Results: At an average follow-up of 22 months (11-39 months), the CS resulted in an average of 81 points. The biceps-specific LHB score showed a mean value of 89 points. The analysis of the DASH score showed an average of 16.9 points and the analysis of the WORC index showed an average result of 79.7 %. Distalization of the biceps muscle was objectively in three cases (7.7 %) (as observed by the examiner) and subjectively in one of those cases (as noted by the patient). There was a loss in elbow flexion strength compared to the contralateral side; however, this loss was not statistically significant and not associated with clinical apparent re-tear or insufficiency of the tenodesis., Discussion: The arthroscopic lasso-loop tenodesis of the LHB tendon is a time and cost-efficient technique. No additional anchor is needed when included in the rotator cuff repair. Functional and cosmetical results as well as results from the biceps-specific LHB score were good to excellent. The loss in elbow flexion strength is most likely associated with concomitant rotator cuff lesion., Conclusion: The lasso-loop fixation technique of the LHB tendon using the antero-medial footprint anchor in rotator cuff tears is a reliable and cost-efficient procedure., Level of Evidence: III.

Tailoring the intrinsic length-scale effects in bulk metallic glasses (BMGs) via post-heat treatment necessitates a systematic analyzing strategy. Although various achievements were made in the past years to structurally enhance the properties of different BMG alloys, the influence of short-term sub-glass transition annealing on the relaxation kinetics is still not fully covered. Here, we aim for unraveling the connection between the physical, (thermo)mechanical and structural changes as a function of selected pre-annealing temperatures and time scales with an in-house developed Cu46Zr44Al8Hf2 based BMG alloy. The controlled formation of nanocrystals below 50 nm with homogenous distribution inside the matrix phase via thermal treatment increase the material's resistance to strain softening by almost an order of magnitude. The present work determines the design aspects of metallic glasses with enhanced mechanical properties via nanostructural modifications, while postulating a counter-argument to the intrinsic property degradation accounted for long-term annealing.

Rotator cuff avulsion fractures represent rare lesions in younger individuals and are caused by different trauma mechanisms. The present article outlines current concepts regarding diagnosis, indications, and surgical approaches to the treatment of greater and lesser tuberosity fractures, as discussed in the international literature. Modified arthroscopic double-row rotator cuff repair techniques allow for the anatomical reduction and retention of fragments and the treatment of concomitant intra-articular lesions at the same time. Moreover, the article provides practical hints on different surgical repair techniques, their respective limitations and results from the literature.

The microstructural evolution of cast Ti/Zr-based bulk metallic glass composites (BMGCs) containing β-Ti still remains ambiguous. This is why to date the strategies and alloys suitable for producing such BMGCs with precisely controllable volume fractions and crystallite sizes are still rather limited. In this work, a Ti-based BMGC containing β-Ti was developed in the Ti-Zr-Cu-Co-Be system. The glassy matrix of this BMGC possesses an exceptional glass-forming ability and as a consequence, the volume fractions as well as the composition of the β-Ti dendrites remain constant over a wide range of cooling rates. This finding can be explained in terms of a two-phase quasi-equilibrium between the supercooled liquid and β-Ti, which the system attains on cooling. The two-phase quasi-equilibrium allows predicting the crystalline and glassy volume fractions by means of the lever rule and we succeeded in reproducing these values by slight variations in the alloy composition at a fixed cooling rate. The two-phase quasi-equilibrium could be of critical importance for understanding and designing the microstructures of BMGCs containing the β-phase. Its implications on the nucleation and growth of the crystalline phase are elaborated.

Background: Reverse shoulder arthroplasty (RSA) is an established therapeutic option in the treatment of cuff tear arthropathy (CTA). Recent studies have described a positive effect of lateralization of the center of rotation, especially on postoperative rotational function. The goal of this study is to compare the outcome of non-lateralized versus lateralized RSA with particular regard to rotational function in patients with CTA., Methods: Thirty-four patients underwent implantation of RSA either with lateralization (n = 17) or without lateralization (n = 17) by use of a 1-cm autologous bone graft ("bony increased offset") of the humeral head for CTA. Clinical outcomes were measured with the Constant score; the Disabilities of the Arm, Shoulder and Hand score; and the Activities of Daily Living Requiring External Rotation score, as well as measurement of external rotation and determination of the external rotation lag sign with the arm at the side and at 90° of abduction, at 1 year postoperatively and at final follow-up. Computed tomography scan evaluation was performed in all patients preoperatively and at 1 year postoperatively to assess preoperative fatty infiltration of the rotator cuff and bony integration of the graft postoperatively., Results: At final follow-up, all patients showed significantly increased functional results. There were no significant differences in the evaluated parameters. If patients with degenerative changes of the teres minor were excluded, the lateralized group showed significantly increased external rotation. Bony integration of the graft could be verified on postoperative computed tomography scans in all patients., Conclusion: RSA with bony lateralization shows a trend toward improved external rotation in lateralized RSA, with a statistically significant improvement in external rotation in patients with an intact teres minor., (Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

An imbalance between matrix metalloproteases (MMPs) and the tissue inhibitors of metalloproteases (TIMPs) may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs). TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

Purpose: Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs., Methods: For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days., Results: Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold., Conclusion: The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects.

Background: Many clinical and radiographic studies suggest that patient age and sex have an influence on rotator cuff (RC) repair outcomes. However, these findings result from retrospective statistical analyses and cannot provide a causal answer., Purpose: To analyze whether age and sex influence the biological potential at the time of RC repair or midterm clinical and radiographic outcomes. Also assessed was the effect of the biological potential on intraindividual clinical/radiographic results., Study Design: Cohort study; Level of evidence, 2., Methods: A total of 40 patients underwent arthroscopic RC repair. At the time of surgery (t = 0), supraspinatus tendon biopsy specimens were obtained, cultivated, and assessed for their biological potential, particularly (1) cell growth and (2) collagen type I production. After a follow-up at 24 months (t = 1), all patients were assessed by clinical scores (Constant score, subjective shoulder value, American Shoulder and Elbow Surgeons [ASES] score, and Western Ontario Rotator Cuff Index [WORC] score) and underwent magnetic resonance imaging to determine RC integrity. The data were examined for age- and sex-related differences and to identify the correlation between biological potential (t = 0) and clinical/radiographic outcome (t = 1)., Results: The follow-up rate for the imaging and clinical evaluation was 100%. Age, but not sex, influenced the biological tendon cell parameters at t = 0. However, there was no effect of age or sex on the clinical and radiographic results at t = 1. Furthermore, no correlation was observed between the initial biological parameters and later clinical outcomes or radiographic RC integrity. Finally, there was no significant difference between intact and nonhealed repairs in terms of the respective clinical scores., Conclusion: Age, but not sex, was found to have a negative effect on RC tendon cell biology. However, neither sex nor, in particular, a higher age influenced repair outcomes after 24 months., (© 2015 The Author(s).)

Unlabelled: High initial fixation strength, mechanical stability and biological healing of the tendon-to-bone interface are the main goals after rotator cuff repair surgery. Advances in the understanding of rotator cuff biology and biomechanics as well as improvements in surgical techniques have led to the development of new strategies that may allow a tendon-to-bone interface healing process, rather than the formation of a fibrovascular scar tissue. Although single-row repair remains the most cost-effective technique to address a rotator cuff tear, some biological intervention has been recently introduced to improve tissue healing and clinical outcome of rotator cuff repair. Animal models are critical to ensure safety and efficacy of new treatment strategies; however, although rat shoulders as well as sheep and goats are considered the most appropriate models for studying rotator cuff pathology, no one of them can fully reproduce the human condition. Emerging therapies involve growth factors, stem cells and tissue engineering. Experimental application of growth factors and platelet-rich plasma demonstrated promising results, but has not yet been transferred into standardized clinical practice. Although preclinical animal studies showed promising results on the efficacy of enhanced biological approaches, application of these techniques in human rotator cuff repairs is still very limited. Randomized controlled clinical trials and post-marketing surveillance are needed to clearly prove the clinical efficacy and define proper indications for the use of combined biological approaches. The following review article outlines the state of the art of rotator cuff repair and the use of growth factors, scaffolds and stem cells therapy, providing future directions to improve tendon healing after rotator cuff repair., Level of Evidence: Expert opinion, Level V.

Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging) and external fixator stiffness (mechanically challenging). From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability) in combination rather than alone.

The healing after rotator cuff surgery is still dissatisfying, and increased muscle fatty infiltration even more impairs the healing success. To achieve sufficient healing after rotator cuff reconstructions, the use of growth factors may be one possibility. The aim of the study was to identify a possible relationship between fatty infiltration of the supraspinatus muscle and cellular biological characteristics and stimulation potential of tenocyte-like cells (TLCs). TLCs of 3 donor groups differing in grade of muscle fatty infiltration were analyzed for their cellular characteristics and were stimulated with BMP-2 or BMP-7 in a 3D scaffold culture. The cell count and potency for self-renewal were significantly decreased in TLCs from donors with high muscle fatty infiltration compared to the lower fatty infiltration groups. Cell count and collagen-I expression as well as protein synthesis were stimulated by growth factors. Interestingly, TLCs of the high fatty infiltration group exhibited a weaker stimulation potential compared to the other groups. TLCs from donors with high muscle fatty infiltration generally revealed inferior characteristics compared to cells of lower fatty infiltration groups, which may be one reason for a weaker healing potential and may represent a possible starting point for the development of future treatment options., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The correlation between the microstructure and mechanical behavior during tensile loading of Ti68.8Nb13.6Al6.5Cu6Ni5.1 and Ti71.8Nb14.1Al6.7Cu4Ni3.4 alloys was investigated. The present alloys were prepared by the non-equilibrium processing applying relatively high cooling rates. The microstructure consists of a dendritic bcc β-Ti solid solution and fine intermetallic precipitates in the interdendritic region. The volume fraction of the intermetallic phases decreases significantly with slightly decreasing the Cu and Ni content. Consequently, the fracture mechanism in tension changes from cleavage to shear. This in turn strongly enhances the ductility of the alloy and as a result Ti71.8Nb14.1Al6.7Cu4Ni3.4 demonstrates a significant tensile ductility of about 14% combined with the high yield strength of above 820 MPa already in the as-cast state. The results demonstrate that the control of precipitates can significantly enhance the ductility and yet maintaining the high strength and the low Young's modulus of these alloys. The achieved high bio performance (ratio of strength to Young's modulus) is comparable (or even superior) with that of the recently developed Ti-based biomedical alloys., (© 2013.)

Tendon bone healing of the rotator cuff is often associated with non-healing or recurrent defects, which seems to be influenced by the patient's age and sex. The present study aims to examine cellular biological characteristics of tenocyte-like cells that may contribute to this impaired rotator cuff healing. Moreover, a therapeutic approach using growth factors could possibly stimulate tendon bone healing. Therefore, our second aim was to identify patient groups who would particularly benefit from growth factor stimulation. Tenocyte-like cells isolated from supraspinatus tendons of female donors younger and older than 65 years of age were characterized with respect to different cellular biological parameters, such as cell density, cell count, marker expression, collagen-I protein synthesis, and stem cell potential. Furthermore, cells of the donor groups were stimulated with BMP-2 and BMP-7 (200 and 1000 ng/ml) in 3D-culture and analyzed for cell count, marker expression and collagen-I protein synthesis. Female donors older than 65 years of age showed significantly decreased cell count and collagen-I protein synthesis compared to cells from donors younger than 65 years. Cellular biological parameters including cell count, collagen-I and -III expression, and collagen-I protein synthesis of cells from both donor groups were stimulated with BMP-2 and BMP-7. The cells from donors older than 65 years revealed a decreased stimulation potential for cell count compared to the younger group. Cells from female donors older than 65 years of age showed inferior cellular biological characteristics. This may be one reason for a weaker healing potential observed in older female patients and should be taken into consideration for tendon bone healing of the rotator cuff.