title: A new 3D concentration gradient maker and its application in building hydrogels with a 3D stiffness gradient.
abstract: For a deeper knowledge of phenomena at cell and tissue level, for understanding the role on bimolecular signalling and for the development of new drugs it is important to recreate in vitro environments that mimic the physiological one. Spatial gradients of soluble species guide the cells' morphogenesis, and they range in a three-dimensional (3D) environment. Gradients of mechanical properties, which have a 3D pattern, could lead cell migration and differentiation. In this work, a new 3D Concentration Gradient Maker able to generate 3D concentration gradients of soluble species was developed, which could be used for differential perfusion of scaffolds. The same device can be applied to build hydrogel matrixes with a 3D gradient of mechanical properties. Computational dynamic fluid analysis was used to develop the gradient generator; the validation of the 3D gradient of stiffness was carried out using finite elements analysis and experimental studies. The device and its application could bring improvements in studying phenomena related to cell chemotaxis and mechanotaxis, but also to differentiation in the simultaneous presence of gradients in both soluble chemical species and substrate stiffness. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Research Centre 'E. Piaggio', University of Pisa, Pisa, Italy.|Department of Ingegneria Civile e Industriale (DICI), University of Pisa, Pisa, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Orsi
authors.affiliation: Research Centre 'E. Piaggio', University of Pisa, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fagnano
authors.affiliation: Research Centre 'E. Piaggio', University of Pisa, Pisa, Italy.|Department of Ingegneria dell'Informazione (DII), University of Pisa, Pisa, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: De Maria
authors.affiliation: Research Centre 'E. Piaggio', University of Pisa, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montemurro
authors.affiliation: Research Centre 'E. Piaggio', University of Pisa, Pisa, Italy.|Department of Ingegneria dell'Informazione (DII), University of Pisa, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vozzi
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D032701:Biomimetics; D019149:Bioreactors; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D002633:Chemotaxis; D003198:Computer Simulation; D055119:Elastic Modulus; D004867:Equipment Design; D006801:Humans; D057446:Hydrodynamics; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D010477:Perfusion; D011092:Polyethylene Glycols / Q000737:chemistry; D013314:Stress, Mechanical
chemical_list: D000178:Acrylamides; D020100:Hydrogels; D011092:Polyethylene Glycols
keywords: bioreactors; chemotaxis; computational fluid dynamics; durotaxis; finite element analysis; polyacrylamide