title: A compressible scaffold for minimally invasive delivery of large intact neuronal networks.
abstract: Millimeter to centimeter-sized injectable neural scaffolds based on macroporous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally invasive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
authors.affiliation: STI-IMT-LMIS4, Station 17, EPFL, 1015, Lausanne, Switzerland.
authors.forename: Amélie
authors.initials: A
authors.lastname: Béduer
authors.forename: Thomas
authors.initials: T
authors.lastname: Braschler
authors.forename: Oliver
authors.initials: O
authors.lastname: Peric
authors.forename: Georg E
authors.initials: GE
authors.lastname: Fantner
authors.forename: Sébastien
authors.initials: S
authors.lastname: Mosser
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Fraering
authors.forename: Sidi
authors.initials: S
authors.lastname: Benchérif
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.forename: Philippe
authors.initials: P
authors.lastname: Renaud
mesh_terms: D000464:Alginates / Q000494:pharmacology; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D059985:Cryogels / Q000494:pharmacology; D016503:Drug Delivery Systems; D020342:Finite Element Analysis; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D007267:Injections; D009474:Neurons / Q000166:cytology*; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D059985:Cryogels; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002266:Carboxymethylcellulose Sodium
keywords: Young modulus; macroporous scaffold; minimally invasive delivery; neuronal network; tissue engineering