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A mesofluidics-based test platform for systematic development of scaffolds for in situ cardiovascular tissue engineering
Periodical: Tissue Eng Part C Methods ISBN: 1937-3392 (Electronic)
1937-3384 (Linking)
Date: 2012/01/10
Language: Eng
Authors:Smits, A., Driessen-Mol, A., Bouten, C., Baaijens, F.
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Abstract
Recently, in situ tissue engineering has emerged as a new approach to obtain autologous, living replacement tissues with off-the-shelf availability. The method is based on the use of an instructive biodegradable scaffold that is capable of repopulation with host cells in situ and subsequent tissue formation. This approach imposes high demands on scaffold properties. For cardiovascular grafts, the repopulation with endogenous cells from the circulation is further hypothesized to be influenced by the hemodynamic environment of the scaffold. In order to systematically study the effect of scaffold properties on the response of circulating cells, we aimed to develop a mesofluidics-based in vitro test platform that enables on-stage investigation of the interaction of circulating cells with 3D synthetic scaffolds under physiologic hemodynamic conditions. The test platform consists of a custom developed cross-flow chamber that houses small-scale 3D scaffolds. The cross-flow chamber is incorporated into a flow-loop to drive a cell suspension along the scaffold with physiological wall shear stress and perfusion pressure. The fluidics system is validated numerically and experimentally using a computational fluid dynamics model and real-time microbead tracing studies, demonstrating a fully developed flow profile with a homogeneous shear stress distribution over the scaffold. Wall shear stresses and pressure can be controlled independently, well within the target physiological range (0-8 Pa and 0-100 mmHg, respectively). Bench-top evaluation is performed using electrospun poly(epsilon-caprolactone) scaffolds with varying fiber diameter, exposed to a suspension of human peripheral blood mononuclear cells in pulsatile flow for 72 hours. Cell adhesion and infiltration are monitored using time-lapsed confocal laser scanning microscopy. In conclusion, we have successfully developed a mesofluidics platform to study cell-scaffold interactions under hemodynamic conditions in vitro. This
Recently, in situ tissue engineering has emerged as a new approach to obtain autologous, living replacement tissues with off-the-shelf availability. The method is based on the use of an instructive biodegradable scaffold that is capable of repopulation with host cells in situ and subsequent tissue formation. This approach imposes high demands on scaffold properties. For cardiovascular grafts, the repopulation with endogenous cells from the circulation is further hypothesized to be influenced by the hemodynamic environment of the scaffold. In order to systematically study the effect of scaffold properties on the response of circulating cells, we aimed to develop a mesofluidics-based in vitro test platform that enables on-stage investigation of the interaction of circulating cells with 3D synthetic scaffolds under physiologic hemodynamic conditions. The test platform consists of a custom developed cross-flow chamber that houses small-scale 3D scaffolds. The cross-flow chamber is incorporated into a flow-loop to drive a cell suspension along the scaffold with physiological wall shear stress and perfusion pressure. The fluidics system is validated numerically and experimentally using a computational fluid dynamics model and real-time microbead tracing studies, demonstrating a fully developed flow profile with a homogeneous shear stress distribution over the scaffold. Wall shear stresses and pressure can be controlled independently, well within the target physiological range (0-8 Pa and 0-100 mmHg, respectively). Bench-top evaluation is performed using electrospun poly(epsilon-caprolactone) scaffolds with varying fiber diameter, exposed to a suspension of human peripheral blood mononuclear cells in pulsatile flow for 72 hours. Cell adhesion and infiltration are monitored using time-lapsed confocal laser scanning microscopy. In conclusion, we have successfully developed a mesofluidics platform to study cell-scaffold interactions under hemodynamic conditions in vitro. This
Keywords
Animals, Capsules, Cell Culture Techniques, Collagen/ pharmacology, Drug Combinations, Fetus/cytology, Immunohistochemistry, Laminin/ pharmacology, Mice, Mice, Inbred BALB C, Proteoglycans/ pharmacology, Pulmonary Alveoli/cytology/embryology/ physiology/ultrastructure, Reverse Transcriptase Polymerase Chain Reaction, Tissue Engineering/ methods, Tissue Scaffolds/ chemistry
Animals, Capsules, Cell Culture Techniques, Collagen/ pharmacology, Drug Combinations, Fetus/cytology, Immunohistochemistry, Laminin/ pharmacology, Mice, Mice, Inbred BALB C, Proteoglycans/ pharmacology, Pulmonary Alveoli/cytology/embryology/ physiology/ultrastructure, Reverse Transcriptase Polymerase Chain Reaction, Tissue Engineering/ methods, Tissue Scaffolds/ chemistry