Effect of Axial Load on the Flexural Properties of an Elastomeric Total Disc Replacement

Study Design. Twelve Cadisc-L devices were subjected to flexion (0°–6°) and extension (0° to -3°) motions at compressive loads between 500 N and 2000 N at a flexural rate between 0.25°/s and 3.0°/s.\ud \ud Objective. To quantify the change in flexural properties of the Cadisc-L (elastomeric device), when subjected to increasing magnitudes of axial load and at different flexural rates.\ud \ud Summary of Background Data. The design of motion preservation devices, used to replace degenerated intervertebral discs, is commonly based on a low-friction, ball-and-socket-articulating joint. Recently, elastomeric implants have been developed that attempt to provide mechanical and motion properties that resemble those of the natural disc more closely.\ud \ud Methods. Twelve Cadisc-L devices (MC-10 mm-9° and MC-10 mm-12° size) were supplied by Ranier Technology Ltd (Cambridge, United Kingdom). The devices were hydrated and tested using a Bose spinal disc-testing machine (Bose Corporation, ElectroForce Systems Group, Eden Prairie, MN) in Ringer's solution at 37°C. A static load of 500 N was applied to a device and it was then subjected to motions of 0° to 6° to 0° (flexion) and 0° to -3° to 0° (extension) at a flexural rate of 0.25°/s, 0.5°/s, 1.0°/s, 1.5°/s, 2.0°/s, and 3.0°/s. Tests were repeated at 1000 N, 1500 N, and 2000 N.\ud \ud Results. Regression analyses showed a significant ($R^2$ > 0.99, $\rho$< 0.05) linear increase in bending moment and flexural stiffness with flexion and extension angles (at 1000 N and higher loads)—a significant ($R^2$> 0.994, $\rho$< 0.05) linear decrease in flexural stiffness in flexion and extension as flexural rate increased.\ud \ud Conclusion. The bending moment of the Cadisc-L increased linearly with flexion and extension angles at 1000 N and higher loads. Flexural stiffness increased with compressive load but decreased with flexural rate.\ud \u

Tailoring selective laser melting process for titanium drug-delivering implants with releasing micro-channels

Ganoderma is a large, diverse and globally-distributed genus in the Basidiomycota that includes species causing a white rot form of wood decay on a variety of tree species. For the past century, many studies of Ganoderma in North America and other regions of the world have used the name G. lucidum sensu lato for any laccate (shiny or varnished) Ganoderma species growing on hardwood trees or substrates. Molecular studies have established that G. lucidum sensu stricto (Curtis) Karst is native to Europe and some parts of China. To determine the species of the laccate Ganoderma that are present in the United States, we studied over 500 collections from recently collected samples and herbarium specimens from hardwoods, conifers, and monocots. A multilocus phylogeny using ITS, tef1α, rpb1 and rpb2 revealed three well-supported clades, similar to previously reported findings. From the U.S. collections, thirteen taxa representing twelve species were identified, including: G. curtisii, G. lucidum sensu stricto, G. martinicense, G. oregonense, G. polychromum, G. ravenelii, G. sessile, G. tsugae, G. tuberculosum, G. cf. weberianum, G. zonatum, and Tomophagus colossus (syn. G. colossus). The species G. meredithiae is synonymized with G. curtisii, and considered a physiological variant that specializes in decay of pines. The designation G. curtisii f.sp. meredithiae forma specialis nov. is proposed. Species such as G. curtisii and G. sessile, once considered as G. lucidum sensu lato, were found to be divergent from one another, and highly divergent from G. lucidum sensu stricto. Morphological characteristics such as context tissue color and features (e.g. melanoid bands), basidiospore shape and size, geographic location, and host preference were found to aid in species identification. Surprisingly, G. lucidum sensu stricto was found in the U.S., but only in geographically restricted areas of northern Utah and California. These collections appear to have resulted from the introduction of this species into the United States possibly from mushroom growers producing G. lucidum outdoors. Overall, this study clarifies the chaotic taxonomy of the laccate Ganoderma in the United States, and will help to remove ambiguities from future studies focusing on the North American species of laccate Ganoderma

The design of additively manufactured lattices to increase the functionality of medical implants

The rise of antibiotic resistant bacterial species is driving the requirement for medical devices that minimise infection risks. Antimicrobial functionality may be achieved by modifying the implant design to incorporate a reservoir that locally releases a therapeutic. For this approach to be successful it is critical that mechanical functionality of the implant is maintained. This study explores the opportunity to exploit the design flexibilities possible using additive manufacturing to develop porous lattices that maximise the volume available for drug loading while maintaining load-bearing capacity of a hip implant. Eight unit cell types were initially investigated and a volume fraction of 30% was identified as the lowest level at which all lattices met the design criteria in ISO 13314. Finite element analysis (FEA) identified three lattice types that exhibited significantly lower displacement (10-fold) compared with other designs; Schwartz primitive, Schwartz primitive pinched and cylinder grid. These lattices were additively manufactured in Ti-6Al-4V using selective laser melting. Each design exceeded the minimum strength requirements for orthopaedic hip implants according to ISO 7206-4. The Schwartz primitive (Pinched) lattice geometry, with 10% volume fill and a cubic unit cell period of 10, allowed the greatest void volume of all lattice designs whilst meeting the fatigue requirements for use in an orthopaedic implant (ISO 7206-4). This paper demonstrates an example of how additive manufacture may be exploited to add additional functionality to medical implants

Adding functionality with additive manufacturing : fabrication of titanium-based antibiotic eluting implants

Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease