Nanoparticulate technologies have revolutionized drug delivery allowing for passive and active targeting, altered biodistribution, controlled drug release (temporospatial or triggered), enhanced stability, improved solubilization capacity, and a reduction in dose and adverse effects. However, their manufacture remains immature, and challenges exist on an industrial scale due to high batch-to-batch variability hindering their clinical translation. Lipid-based nanomedicines remain the most widely approved nanomedicines, and their current manufacturing methods remain discontinuous and face several problems such as high batch-to-batch variability affecting the critical quality attributes (CQAs) of the product, laborious multistep processes, need for an expert workforce, and not being easily amenable to industrial scale-up involving typically a complex process control. Several techniques have emerged in recent years for nanomedicine manufacture, but a paradigm shift occurred when microfluidic strategies able to mix fluids in channels with dimensions of tens of micrometers and small volumes of liquid reagents in a highly controlled manner to form nanoparticles with tunable and reproducible structure were employed. In this review, we summarize the recent advancements in the manufacturing of lipid-based nanomedicines using microfluidics with particular emphasis on the parameters that govern the control of CQAs of final nanomedicines. The impact of microfluidic environments on formation dynamics of nanomaterials, and the application of microdevices as platforms for nanomaterial screening are also discussed.

This paper is concerned with proposing a suitable structurally motivated strain energy function, denoted by Weelastin network, for modeling the deformation of the elastin network within the aortic valve (AV) tissue. The AV elastin network is the main noncollagenous load-bearing component of the valve matrix, and therefore, in the context of continuum-based modeling of the AV, the Weelastin network strain energy function would essentially serve to model the contribution of the “isotropic matrix.” To date, such a function has mainly been considered as either a generic neo-Hookean term or a general exponential function. In this paper, we take advantage of the established structural analogy between the network of elastin chains and the freely jointed molecular chain networks to customize a structurally motivated Weelastin network function on this basis. The ensuing stress–strain (force-stretch) relationships are thus derived and fitted to the experimental data points reported by (Vesely, 1998, “The Role of Elastin in Aortic Valve Mechanics,” J. Biomech., 31, pp. 115–123) for intact AV elastin network specimens under uniaxial tension. The fitting results are then compared with those of the neo-Hookean and the general exponential models, as the frequently used models in the literature, as well as the “Arruda–Boyce” model as the gold standard of the network chain models. It is shown that our proposed Weelastin network function, together with the general exponential and the Arruda–Boyce models provide excellent fits to the data, with R2 values in excess of 0.98, while the neo-Hookean function is entirely inadequate for modeling the AV elastin network. However, the general exponential function may not be amenable to rigorous interpretation, as there is no structural meaning attached to the model. It is also shown that the parameters estimated by the Arruda–Boyce model are not mathematically and structurally valid, despite providing very good fits. We thus conclude that our proposed strain energy function Weelastin network is the preferred choice for modeling the behavior of the AV elastin network and thereby the isotropic matrix. This function may therefore be superimposed onto that of the anisotropic collagen fibers family in order to develop a structurally motivated continuum-based model for the AV.

A new anisotropic viscoelastic model is developed for application to the aortic valve (AV). The directional dependency in the mechanical properties of the valve, arising from the predominantly circumferential alignment of collagen fibres, is accounted for in the form of transverse isotropy. The rate dependency of the valve's mechanical behaviour is considered to stem from the viscous ( η ) dissipative effects of the AV matrix, and is incorporated as an explicit function of the deformation rate ( λ ˙ ). Model (material) parameters were determined from uniaxial tensile deformation tests of porcine AV specimens at various deformation rates, by fitting the model to each experimental dataset. It is shown that the model provides an excellent fit to the experimental data across all different rates and satisfies the condition of strict local convexity. Based on the fitting results, a nonlinear relationship between η and λ ˙ is established, highlighting a ‘shear-thinning’ behaviour for the AV with increase in the deformation rate. Using the model and these outcomes, the stress–deformation curves of the AV tissue under physiological deformation rates in both the circumferential and radial directions are predicted and presented. To verify the predictive capabilities of the model, the stress–deformation curves of AV specimens at an intermediate deformation rate were estimated and validated against the experimental data at that rate, showing an excellent agreement. While the model is primarily developed for application to the AV, it may be applied without the loss of generality to other collagenous soft tissues possessing a similar structure, with a single preferred direction of embedded collagen fibres.

This paper presents an experimental investigation and evidence of rate-dependency in the planar mechanical behaviour of semilunar heart valves. Samples of porcine aortic and pulmonary valves were subjected to biaxial deformations across 1000-fold stretch rate, ranging from λ̇=0.001 to 1 s-1. The experimental campaign encompassed protocols covering (i) tests on samples without preconditioning, (ii) preconditioning immediately followed by tensile tests; and (iii) tensile tests at different rates performed on the same preconditioned specimen. Our results indicate that under all employed loading protocols, heart valve samples exhibit a marked rate-dependency in their deformation behaviour. This rate-dependency is reflected in stress-stretch curves and the calculated ensuing gradients, where samples typically show stiffening with increased rate. These results underpin one conclusive outcome: the in-plane mechanical behaviour of semilunar valves is rate-dependent (p<0.05 for Cauchy stress levels ≥50 kPa). This outcome implies that the rate of deformation for characterising the mechanical behaviour of semilunar heart valves may not be chosen arbitrarily low, and models that incorporate rate-effects may be more appropriate for better capturing the mechanical behaviour of heart valves. STATEMENT OF SIGNIFICANCE: This study presents for the first time a comprehensive set of results and evidence of rate-dependency in the mechanical behaviour of semilunar heart valves under biaxial deformation. Our results challenge the widely-applied assumption in the bulk of the existing literature, where an implicit rate-independency is assumed in both experimental and modelling propositions related to the biomechanics of the aortic and pulmonary valves. This study therefore creates a solid platform for future research in heart valve biomechanics with two important implications. First, experimental campaigns have to be carried out at high stretch rates; ideally as close to the physiological rate as possible. Second, new continuum/computational models are required to address the rate-dependent mechanical behaviour of the semilunar valves.

Azhdarchid pterosaurs, the largest flying vertebrates, remain poorly understood, with fundamental aspects of their palaeobiology unknown. X-ray computed tomography reveals a complex internal micro-architecture for three-dimensionally preserved, hyper-elongate cervical vertebrae of the Cretaceous azhdarchid pterosaur, Alanqa sp. Incorporation of the neural canal within the body of the vertebra and elongation of the centrum result in a “tube within a tube” supported by helically distributed trabeculae. Linear elastic static analysis and linearized buckling analysis, accompanied with a finite element model, reveal that as few as 50 trabeculae increase the buckling load by up to 90%, implying that a vertebra without the trabeculae is more prone to elastic instability due to axial loads. Subsuming the neural tube into the centrum tube adds considerable stiffness to the cervical series, permitting the uptake of heavy prey items without risking damage to the cervical series, while at the same time allowing considerable skeletal mass reduction.