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Muscle shortening and volume displacement (VD) are critical determinants of the pressure-generating capacity of the diaphragm. The present study was designed to test the hypothesis that diaphragm VD is heterogeneous and that distribution of VD is dependent on regional muscle shortening, posture, and the level of muscle activation. Radioopaque markers were sutured along muscle bundles of the peritoneal surface of the crural, dorsal costal, midcostal, and ventral costal regions of the left hemidiaphragm in four dogs. The markers were followed by biplanar video fluoroscopy during quiet spontaneous breathing, passive inflation to total lung capacity (TLC), and inspiratory efforts against an occluded airway at three lung volumes spanning the vital capacity [functional residual capacity, functional residual capacity + ½ inspiratory capacity, and TLC in both the prone and supine postures]. Our data show the ventral costal diaphragm had the largest VD and contributed nearly two times to the total diaphragm VD compared with the dorsal costal portion. In addition, the ventral costal diaphragm contributed nearly half of the total VD in the prone position, whereas it only contributed a quarter of the total VD in the supine postition. During efforts against an occluded airway and during passive inflation to TLC in the supine position, the crural diaphragm displaced volume equivalent to that of the midcostal portion. Regional muscle shortening closely matched regional VD. We conclude that the primary force generator of the diaphragm is primarily dominated by the contribution of the ventral costal region to its VD., (Copyright © 2017 the American Physiological Society.)

Minimization schema in nature affects the material arrangements of most objects, independent of scale. The field of cellular solids has focused on the generalization of these natural architectures (bone, wood, coral, cork, honeycombs) for material improvement and elucidation into natural growth mechanisms. We applied this approach for the comparison of a set of complex three-dimensional (3D) architectures containing the same material volume but dissimilar architectural arrangements. Ball and stick representations of these architectures at varied material volumes were characterized according to geometric properties, such as beam length, beam diameter, surface area, space filling efficiency, and pore volume. Modulus, deformation properties, and stress distributions as contributed solely by architectural arrangements was revealed through finite element simulations. We demonstrated that while density is the greatest factor in controlling modulus, optimal material arrangement could result in equal modulus values even with volumetric discrepancies of up to 10%. We showed that at low porosities, loss of architectural complexity allows these architectures to be modeled as closed celled solids. At these lower porosities, the smaller pores do not greatly contribute to the overall modulus of the architectures and that a stress backbone is responsible for the modulus. Our results further indicated that when considering a deposition-based growth pattern, such as occurs in nature, surface area plays a large role in the resulting strength of these architectures, specifically for systems like bone. This completed study represents the first step towards the development of mathematical algorithms to describe the mechanical properties of regular and symmetric architectures used for tissue regenerative applications. The eventual goal is to create logical set of rules that can explain the structural properties of an architecture based solely upon its geometry. The information could then be used in an automatic fashion to generate patient-specific scaffolds for the treatment of tissue defects.

The goal of this area of research is to manipulate the pore space of scaffolds through the application of an intelligent design concept on dissolvable microparticles. To accomplish this goal, we developed an efficient and repeatable process for fabrication of microparticles from multiple materials using a combination of rapid prototyping (RP) and soft lithography. Phase changed 3D printing was used to create masters for PDMS molds. A photocrosslinkable polymer was then delivered into these molds to make geometrically complex 3D microparticles. This repeatable process has demonstrated to generate the objects with greater than 95% repeatability with complete pattern transfer. This process was illustrated for three different shapes of various complexities. The shapes were based on the extrusion of 2D shapes. This may allow simplification of the fabrication process in the future combined with a direct transfer of the findings. Altering the shapes of particles used for porous scaffold fabrication will allow for tailoring of the pore shapes, and therefore their biological function within a porous tissue engineering scaffold. Through permeation experiments, we have shown that the pore geometry may alter the permeability coefficient of scaffolds while influencing mechanical properties to a lesser extent. By selecting different porogen shapes, the nutrition transport and scaffold degradation can be significantly influenced with minimal effect on the mechanical integrity of the construct. In addition, the different shapes may allow a control of drug release by modifying their surface-to-volume ratio, which could modulate drug delivery over time. While soft lithography is currently used with photolithography, its high precision is offset by high cost of production. The employment of RP to a specific resolution offers a much less expensive alternative with increased throughput due to the speed of current RP systems.

During physiological spontaneous breathing maneuvers, the diaphragm displaces volume while maintaining curvature. However, with maximal diaphragm activation, curvature decreases sharply. We tested the hypotheses that the relationship between diaphragm muscle shortening and volume displacement (VD) is nonlinear and that curvature is a determinant of such a relationship. Radiopaque markers were surgically placed on three neighboring muscle fibers in the midcostal region of the diaphragm in six dogs. The three-dimensional locations were determined using biplanar fluoroscopy and diaphragm VD, curvature, and muscle shortening were computed in the prone and supine postures during spontaneous breathing (SB), spontaneous inspiration efforts after airway occlusion at lung volumes ranging from functional residual capacity (FRC) to total lung capacity, and during bilateral maximal phrenic nerve stimulation at those same lung volumes. In supine dogs, diaphragm VD was approximately two- to three-fold greater during maximal phrenic nerve stimulation than during SB. The contribution of muscle shortening to VD nonlinearly increases with level of diaphragm activation independent of posture. During submaximal diaphragm activation, the contribution is essentially linear due to constancy of diaphragm curvature in both the prone and supine posture. However, the sudden loss of curvature during maximal bilateral phrenic nerve stimulation at muscle shortening values greater than 40% (ΔL/L(FRC)) causes a nonlinear increase in the contribution of muscle shortening to diaphragm VD, which is concomitant with a nonlinear change in diaphragm curvature. We conclude that the nonlinear relationship between diaphragm muscle shortening and its VD is, in part, due to a loss of its curvature at extreme muscle shortening.