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We investigate the circulation of nano- and micro-particles, including spherical particles and filamentous nanoworms, with red blood cells (RBCs) suspension in a constricted channel that mimics a stenosed microvessel. Through three-dimensional simulations using the immersed boundary-based Lattice Boltzmann method, the influence of channel geometries, such as the length and ratio of the constriction, on the accumulation of particles is systematically studied. Firstly, we find that the accumulation of spherical particles with 1 μm diameter in the constriction increases with the increases of both the length and ratio of the constriction. This is attributed to the interaction between spheres and RBCs. The RBCs “carry” the spheres and they accumulate inside the constriction together, due to the altered local hydrodynamics induced by the existence of the constriction. Secondly, nanoworms demonstrate higher accumulation than that of spheres inside the constriction, which is associated with the escape of nanoworms from RBC clusters and their accumulation near the wall of main channel. The accumulated near-wall nanoworms will eventually enter the constriction, thus enhancing their concentration inside the constriction. However, an exceptional case occurs in the case of constrictions with large ratio and long length. In such circumstances, the RBCs aggregate together tightly and concentrate at the center of the channel, which makes the nanoworms hardly able to escape from RBC clusters, leading to a similar accumulation of nanoworms and spheres inside the constriction. This study may provide theoretical guidance for the design of nano- and micro-particles for biomedical engineering applications, such as drug delivery systems for patients with stenosed microvessels. 

In vitroevaluations provide vital information on the ability of tissue engineered scaffolds to support cell life and promote natural physiological behaviors in culture. Such assessments are necessary to conduct before implementation of the scaffolds for tissue healingin vivo. The scaffold extracellular matrix must provide the biochemical and mechanical cues necessary to promote cellular attachment, migration and proliferation before differentiation and new tissue deposition can occur. In this study, anin vitroevaluation was conducted to assess the ability of scaffolds three‐dimensional (3D) printed with a previously developed alginate‐polyvinyl alcohol‐hydroxyapatite formulation to promote proliferation of encapsulated MC3T3 cells. A systematic investigation was conducted to increase cell proliferation, and it was determined that the concentration and duration of the calcium bath have a less effect on proliferation than the composition of the formulation itself. Collagen gel was incorporated into the formulation to provide cells with adhesion sites necessary to sufficiently attach to the matrix. Enhanced proliferation was achieved within scaffolds of increased collagen content and sufficient crosslinking. This highlighted the importance of the synergistic effect created as a result of sufficient ligand density coupled with appropriate scaffold mechanical rigidity to provide a suitable environment for proliferation. Thus, these 3D printed tri‐polymer scaffolds have the ability to support cell proliferation and have potential to promote cell differentiation and new bone tissue deposition. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3262–3272, 2017.

 

The zonal organization of osteochondral tissue underlies its long term function. Despite this, tissue engineering strategies targeted for osteochondral repair commonly rely on the use of isotropic biomaterials for tissue reconstruction. There exists a need for a new class of highly biomimetic, anisotropic scaffolds that may allow for the engineering of new tissue with zonal properties. To address this need, we report the facile production of monolithic multidirectional collagen‐based scaffolds that recapitulate the zonal structure and composition of osteochondral tissue. First, superficial and osseous zone‐mimicking scaffolds were fabricated by unidirectional freeze casting collagen‐hyaluronic acid and collagen‐hydroxyapatite‐containing suspensions, respectively. Following their production, a lyophilization bonding process was used to conjoin these scaffolds with a distinct collagen‐hyaluronic acid suspension mimicking the composition of the transition zone. Resulting matrices contained a thin, highly aligned superficial zone that interfaced with a cellular transition zone and vertically oriented calcified cartilage and osseous zones. Confocal microscopy confirmed a zone‐specific localization of hyaluronic acid, reflecting the depth‐dependent increase of glycosaminoglycans in the native tissue. Poorly crystalline, carbonated hydroxyapatite was localized to the calcified cartilage and osseous zones and bordered the transition zone. Compressive testing of hydrated scaffold zones confirmed an increase of stiffness with scaffold depth, where compressive moduli of chondral and osseous zones fell within or near ranges conducive for chondrogenesis or osteogenesis of mesenchymal stem cells. With the combination of these biomimetic architectural and compositional cues, these multidirectional scaffolds hold great promise for the engineering of zonal osteochondral tissue. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 948–958, 2018.