title: Cellulose Nanofibril Hydrogel Tubes as Sacrificial Templates for Freestanding Tubular Cell Constructs.
abstract: The merging of defined nanoscale building blocks with advanced additive manufacturing techniques is of eminent importance for the preparation of multiscale and highly functional materials with de novo designed hierarchical architectures. Here, we demonstrate that hydrogels of cellulose nanofibrils (CNF) can be processed into complex shapes, and used as a sacrificial template to prepare freestanding cell constructs. We showcase our approach for the fabrication of hollow fibers using a controlled extrusion through a circular die into a coagulation bath. The dimensions of the hollow fibers are tunable, and the final tubes combine the nanofibrillar porosity of the CNF hydrogel with a submillimeter wall thickness and centimeter-scale length provided by the additive manufacturing technique. We demonstrate that covalent and supramolecular cross-linking of the CNFs can be used to tailor the mechanical properties of the hydrogel tubes within 1 order of magnitude and in an attractive range for the mechanosensation of cells. The resulting tubes are highly biocompatible and allow for the growth of mouse fibroblasts into confluent cell layers in their inner lumen. A detailed screening of several cellulases enables degradation of the scaffolding, temporary CNF hydrogel tube in a quick and highly cell-friendly way, and allows the isolation of coherent cell tubes. We foresee that the growing capabilities of hydrogel printing techniques in combination with the attractive features of CNFs-sustainable, globally abundant, biocompatible and enzymatically degradable-will allow making plant-based biomaterials with hierarchical structures and on-demand degradation useful, for instance, to engineer complex tissue structures to replace animal models, and for implants.
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, 52074 Aachen, Germany.
authors.forename: Jose Guillermo
authors.initials: JG
authors.lastname: Torres-Rendon
authors.affiliation: Dental Materials and Biomaterials Research, RWTH Aachen University Hospital , Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Köpf
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, 52074 Aachen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Gehlen
authors.affiliation: Dental Materials and Biomaterials Research, RWTH Aachen University Hospital , Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Blaeser
authors.affiliation: Dental Materials and Biomaterials Research, RWTH Aachen University Hospital , Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Fischer
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, 52074 Aachen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: De Laporte
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, 52074 Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Walther
mesh_terms: D000818:Animals; D002460:Cell Line; D002480:Cellulase / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives*; D005347:Fibroblasts / Q000187:drug effects; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry*; D055595:Mechanical Phenomena; D051379:Mice; D043942:Nanotubes / Q000009:adverse effects / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D002482:Cellulose; D002480:Cellulase