Recent studies have identified a specialized subset of CD31hiEMCNhi vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31hiEMCNhi endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31hiEMCNhi endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of Slit3 reduced skeletal CD31hiEMCNhi endothelium, resulted in low bone mass due to impaired bone formation and partially reversed the high bone mass phenotype of Shn3−/− mice. This coupling between osteoblasts and CD31hiEMCNhi endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone-fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss.
Aims This combined clinical and in vitro study aimed to determine the incidence of liner malseating in modular dual mobility (MDM) constructs in primary total hip arthroplasties (THAs) from a large volume arthroplasty centre, and determine whether malseating increases the potential for fretting and corrosion at the modular metal interface in malseated MDM constructs using a simulated corrosion chamber. Methods For the clinical arm of the study, observers independently reviewed postoperative radiographs of 551 primary THAs using MDM constructs from a single manufacturer over a three-year period, to identify the incidence of MDM liner-shell malseating. Multivariable logistic regression analysis was performed to identify risk factors including age, sex, body mass index (BMI), cup design, cup size, and the MDM case volume of the surgeon. For the in vitro arm, six pristine MDM implants with cobalt-chrome liners were tested in a simulated corrosion chamber. Three were well-seated and three were malseated with 6° of canting. The liner-shell couples underwent cyclic loading of increasing magnitudes. Fretting current was measured throughout testing and the onset of fretting load was determined by analyzing the increase in average current. Results The radiological review identified that 32 of 551 MDM liners (5.8%) were malseated. Malseating was noted in all of the three different cup designs. The incidence of malseating was significantly higher in low-volume MDM surgeons than high-volume MDM surgeons (p < 0.001). Pristine well-seated liners showed significantly lower fretting current values at all peak loads greater than 800 N (p < 0.044). Malseated liner-shell couples had lower fretting onset loads at 2,400 N. Conclusion MDM malseating remains an issue that can occur in at least one in 20 patients at a high-volume arthroplasty centre. The onset of fretting and increased fretting current throughout loading cycles suggests susceptibility to corrosion when this occurs. These results support the hypothesis that malseated liners may be at risk for fretting corrosion. Clinicians should be aware of this phenomenon. Cite this article: Bone Joint J 2020;102-B(7 Supple B):20–26.
Mechanically assisted crevice corrosion (MACC) is a mechanism for trunnion damage in total hip arthroplasties (THAs). Retrieval studies have shown reduced MACC-related damage for ceramic heads compared with cobalt-chromium (CoCr) heads. We propose that ceramic heads demonstrate fretting at higher cyclic compressive loads than CoCr heads on titanium alloy trunnions in a simulated corrosion model. A closed electrochemical chamber was used to measure fretting current onset loads for two modern titanium alloy trunnions (Zimmer 12/14 and Stryker V-40) in which trunnion failure has been reported. Ceramic and CoCr alloy 36 + 0 mm heads were impacted on each trunnion and cyclically loaded at 3 Hz with increasing magnitude from 100 to 3,400 N for 540 cycles. Onset load was the cyclic compressive load at which the slope of the average fretting current increased significantly. A CoCr head with V40 trunnion demonstrated the lowest onset load (1,400 N), while the V40 trunnion with a ceramic head showed the highest onset load (2,200 N). Significant differences occurred in average fretting current between head materials for V40 trunnions (p < 0.001) at loads over 2,000 N. CoCr-12/14 and ceramic-12/14 couples demonstrated similar onset loads (2,000 N). All head-trunnion combinations showed cyclical fretting response to loading at 100 N. Head material composition was observed to increase fretting at the taper junction but the effect was taper geometry dependent. Using ceramic heads may reduce the phenomena of trunnion fretting and corrosion but the effect of both trunnion geometry and metallurgy warrants further investigation. Statement of clinical significance: Trunnion corrosion may occur with titanium alloy stems regardless of the head material used. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1630-1636, 2018.
The results from this study suggest that patients with well-functioning THAs using polyethylene bearing surfaces with alumina or CoCr heads appear to be at low risk for trunnion corrosion for the specific CoCr alloy stems and trunnion geometries analyzed here.
Recent designs of ankle-foot orthoses (AFOs) have been influenced by the increasing demand for higher function from active individuals. The biomechanical function of the individual and device is dependent upon the underlying mechanical characteristics of the AFO. Prior mechanical testing of AFOs has primarily focused on rotational stiffness to provide insight into expected functional outcomes; mechanical characteristics pertaining to energy storage and release have not yet been investigated. A pseudostatic bench testing method is introduced to characterize compressive stiffness, device deflection, and motion of solid-ankle, anterior floor reaction, posterior leaf spring, and the intrepid dynamic exoskeletal orthosis (IDEO) AFOs. Each of these four AFOs, donned over a surrogate limb, were compressively loaded at different joint angles to simulate the foot-shank orientation during various subphases of stance. In addition to force-displacement measurements, deflection of each AFO strut and rotation of proximal and supramalleolar segments were analyzed. Although similar compressive stiffness values were observed for AFOs designed to reduce ankle motion, the corresponding strut deflection profile differed based on the respective fabrication material. For example, strut deflection of carbon-fiber AFOs resembled column buckling. Expanded clinical test protocols to include quantification of AFO deflection and rotation during subject use may provide additional insight into design and material effects on performance and functional outcomes, such as energy storage and release.
Background: The effect of interportal (IP) capsulotomy, short T-capsulotomy, and long T-capsulotomy, and their repairs, on resistance to anterior and posterior “at risk for dislocation” positions has not been quantified. Hypotheses: Our primary hypothesis was that an IP capsulotomy would have a minimal effect on hip resistive torque compared with both short and long T-capsulotomies in the at-risk dislocation positions. Our secondary hypothesis was that capsule repair would significantly increase hip resistive torque for all capsulotomies. Study Design Controlled laboratory study. Methods: We mounted 10 cadaveric hips on a biaxial test frame in an anterior dislocation high-risk position (20° of hip extension and external rotation) and posterior dislocation high-risk position (90° of hip flexion and internal rotation). An axial force of 100 N was applied to the intact hip while the femur was internally or externally rotated at 15° per second to a torque of 5 N·m. The rotatory position at 5 N·m was recorded and set as a target for each subsequent condition. Hips were then sequentially tested with IP, short T-, and long T-capsulotomies and with corresponding repairs randomized within each condition. Peak resistive torques were compared using generalized estimating equation modeling and post hoc Bonferroni-adjusted tests. Results: For the anterior position, the IP and long T-capsulotomies demonstrated significantly lower resistive torques compared with intact. For the posterior position, both the short and long T-capsulotomies resulted in significantly lower resistive torques compared with intact. Repairs for all 3 capsulotomy types were not significantly different from the intact condition at anterior and posterior positions. Conclusion: An IP incision resulted in a decrease in capsular resistive torque in the anterior but not the posterior at-risk dislocation position, in which direction only T-capsulotomies led to a significant decrease. All capsulotomy repair conditions resulted in hip resistive torques that were similar to the intact hip in both dislocation positions. Clinical Relevance Our results suggest that it is biomechanically advantageous to repair IP, short T-, and long T-capsulotomies, particularly for at-risk anterior dislocation positions.
An automated stochastic docking program with a graphical user interface, RANDOMDOCK (RD), has been developed to aid the development of molecularly imprinted polymers and xerogels. RD supports computations with ab initio and semiempirical quantum chemistry programs. The RD algorithms have been tested by searching for the most stable geometries of a varying number of methacrylic acid molecules interacting with nicotinamide. The optimal structures found are either as stable or more stable than those previously proposed for this molecularly imprinted polymer, illustrating that RD is capable of identifying the lowest-energy structures out of a potentially vast number of possible configurations. RD was subsequently applied to determine the most favorable binding sites between silane molecules and tetracycline (TC) as well as TC analogues. Hydrogen bonding between the templates and a silane is an important determinant of stability. Dispersion interactions are also sizable, sometimes dominant, especially between the largest silane and TC analogues not possessing a site readily available for hydrogen bonding. We highlight the importance of exploring the full intermolecular potential energy landscape when studying systems which may not afford highly specific interactions.
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