title: Versatile fabrication of vascularizable scaffolds for large tissue engineering in bioreactor.
abstract: Despite significant progresses were achieved in tissue engineering over the last 20 years, a number of unsolved problems still remain. One of the most relevant issues is the lack of a proper vascularization that is limiting the size of the engineered tissues to smaller than clinically relevant dimensions. Sacrificial molding holds great promise to engineered construct with perfusable vascular architectures, but there is still the need to develop more versatile approaches able to be independent of the nature and dimensions of the construct. In this work we developed a versatile sacrificial molding technique for fabricating bulk, cell-laden and porous scaffolds with embedded vascular fluidic networks. These branched fluidic architectures are created by highly resistant thermoplastic sacrificial templates, made of poly(vinyl alcohol), representing a remarkable progress in manufacturability and scalability. The obtained architecture, when perfused in bioreactor, has shown to prevent the formation of a necrotic core in thick cell-laden constructs and enabled the rapid fabrication of hierarchically branched endothelium. In conclusion we demonstrate a novel strategy towards the engineering of vascularized thick tissues through the integration of the PVA-based microfabrication sacrificial approach and perfusion bioreactors. This approach may be able to scale current engineered tissues to clinically relevant dimensions, opening the way to their widespread clinical applications.
authors: SEMM, European School of Molecular Medicine, Campus IFOM-IEO, Via Adamello 16, 20139 Milano, Italy; Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Alessandro
authors: A
authors: Tocchio
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Margherita
authors: M
authors: Tamplenizza
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Federico
authors: F
authors: Martello
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Irini
authors: I
authors: Gerges
authors: SEMM, European School of Molecular Medicine, Campus IFOM-IEO, Via Adamello 16, 20139 Milano, Italy.
authors: Eleonora
authors: E
authors: Rossi
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Simona
authors: S
authors: Argentiere
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors: Simona
authors: S
authors: Rodighiero
authors: School of Mechanical and Electronic Engineering, Wuhan University of Technology, 122 Luoshi Road, 430070 Wuhan, Hubei, PR China.
authors: Weiwei
authors: W
authors: Zhao
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milano, Italy. Electronic address: paolo.milani@mi.infn.it.
authors: Paolo
authors: P
authors: Milani
authors: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy; CIMaINa, Dipartimento di Fisica, Università degli Studi di Milano, Via Celoria 16, 20133 Milano, Italy. Electronic address: cristina.lenardi@unimi.it.
authors: Cristina
authors: C
authors: Lenardi
mesh_terms: D000818:Animals; D019149:Bioreactors; D002470:Cell Survival; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005782:Gels; D051379:Mice; D044085:Microfluidics; D055616:Microtechnology; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic; D061848:Optical Imaging; D016062:Porosity; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005782:Gels
keywords: Bioreactor; Sacrificial molding; Scaffolds; Tissue engineering; Vascularization