title: Development and analysis of multi-layer scaffolds for tissue engineering.
abstract: The development of 3D scaffolds consisting of stacked multi-layered porous sheets featuring microchannels is proposed and investigated in this work. In this concept, the inner-porosity of the sheets allows diffusion of nutrients and signalling products between the layers whereas the microchannels facilitate nutrient supply on all layers as they provide space for the culture medium to be perfused throughout the scaffold. Besides the above, these scaffolds have excellent distribution of the cells as seeding and attaching of the cells occurs on individual layers that are subsequently stacked. In addition, these scaffolds enable gaining local data from within the scaffolds as unstacking of the stacked layers allows for determination of various parameters per layer. Here, we show the proof of this concept by culturing C2C12 pre-myoblasts and A4-4 cells on stacked Poly(l-lactic acid) (PLLA) sheets featuring microchannels. The results obtained for culturing under static conditions clearly indicate that despite inhibited cell proliferation due to nutrient limitations, diffusion between the layers takes place and cells on various layers stay viable and also affect each other. Under dynamic conditions, medium flow through the channels improves nutrient availability to the cells on the various layers, drastically increasing cell proliferation on all layers.
authors.affiliation: Membrane Science and Technology, Faculty of Science and Technology, Institute for Biomedical Technology and Technical Medicine (MIRA), University of Twente, P.O. Box 217, 7500 AE, Enschede, The Netherlands.
authors.forename: Bernke J
authors.initials: BJ
authors.lastname: Papenburg
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Higuera
authors.forename: Ana M C
authors.initials: AM
authors.lastname: Barradas
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
authors.forename: Matthias
authors.initials: M
authors.lastname: Wessling
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stamatialis
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008853:Microscopy; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D011091:Polyesters; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)